17q12 Recurrent Deletion Syndrome

Marissa W Mitchel; Daniel Moreno-De-Luca; Scott M Myers; Rebecca V Levy; Stefanie Turner; David H Ledbetter; Christa L Martin

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17q12 Recurrent Deletion Syndrome

Marissa W Mitchel, MS, CCC-SLP, Daniel Moreno-De-Luca, MD, MSc, Scott M Myers, MD, Rebecca V Levy, BM BCh, MSc, Stefanie Turner, MS, CGC, David H Ledbetter, PhD, FACMG, and Christa L Martin, PhD, FACMG.

Author Information and Affiliations

Initial Posting: December 8, 2016; Last Update: February 6, 2025.

Estimated reading time: 53 minutes

Summary

Clinical characteristics.

17q12 recurrent deletion syndrome is characterized by variable combinations of the three following findings: structural or functional abnormalities of the kidney and urinary tract, maturity-onset diabetes of the young type 5 (MODY5), and neurodevelopmental or neuropsychiatric disorders (e.g., developmental delay, intellectual disability, autism spectrum disorder [ASD], attention-deficit/hyperactivity disorder [ADHD], schizophrenia, anxiety, and bipolar disorder). Using a method of data analysis that avoids ascertainment bias, the authors determined that multicystic kidneys and other structural and functional kidney anomalies occur in 85%-90% of affected individuals, MODY5 in approximately 40%, and some degree of developmental delay or learning disability in approximately 50%. MODY5 is most often diagnosed before age 25 years (range: age 10-50 years).

Diagnosis/testing.

The diagnosis is established in a proband by detection of the 1.4-Mb heterozygous recurrent deletion at chromosome 17q12 by chromosomal microarray testing or other genomic methods.

Management.

Treatment of manifestations: Treatment of kidney disease, neurodevelopmental and neuropsychiatric disorders, MODY5, genital tract abnormalities, liver abnormalities, hyperparathyroidism, eye abnormalities, exocrine pancreatic insufficiency, congenital heart defects, seizures, and sensorineural hearing loss should follow standard practice.

Surveillance: Kidneys and urinary tract: In the absence of known structural abnormalities, kidney and bladder ultrasound examination 12 months after establishing the diagnosis, then every two to three years in childhood/adolescence, then every three to five years in adulthood; presence of an abnormality may warrant more frequent monitoring. Monitor blood pressure, kidney function, serum concentration of magnesium, potassium, uric acid, urine magnesium, creatinine, and protein-to-creatinine ratio with frequency per nephrologist; more frequent monitoring may be advised in those with lab findings of kidney disease, those who are taking potentially nephrotoxic medications, and/or those with genitourinary structural abnormalities. Assess developmental progress and educational needs at each visit throughout childhood and adolescence; assess for features of ASD and ADHD at each visit in early childhood; full psychoeducational evaluation for children who experience difficulty with school or behavioral changes; assess for prodromal psychotic symptoms and bipolar disorder at each visit in adolescence. Annual hemoglobin A1c; educate individuals and their families for clinical signs and symptoms of diabetes mellitus. Consider reevaluation for uterine and vaginal abnormalities related to müllerian duct aplasia in pubertal females with primary amenorrhea. Hepatic function panel and GGT periodically; consider periodic lipid panel. Annual serum calcium and phosphorus to assess for hyperparathyroidism; annual ophthalmologic evaluation during early childhood. Fecal elastase-1 to test for exocrine pancreatic insufficiency in individuals with suggestive signs and symptoms. Monitor those with seizures as clinically indicated. Hearing screening throughout childhood.

Agents/circumstances to avoid: Because kidney transplantation increases the risk for post-transplant diabetes mellitus, an immunosuppressive regimen that avoids tacrolimus and mTOR inhibitors and reduces corticosteroid exposure may benefit those without preexisting diabetes mellitus. Nephrotoxic and hepatotoxic drugs should be avoided by individuals with kidney or liver abnormalities. For individuals with mental health conditions (e.g., ASD, schizophrenia, or bipolar disorder), careful consideration of antipsychotic agents that may lead to weight gain, as this may lead to metabolic syndrome and diabetes mellitus, for which individuals with 17q12 recurrent deletion syndrome are at increased risk. Mood stabilizers that affect kidney function in the long term, such as lithium, should be carefully considered in the setting of potential underlying anatomic and functional kidney abnormalities.

Evaluation of relatives at risk: If one of the proband's parents has the 17q12 recurrent deletion, it is appropriate to test older and younger sibs of the proband and other relatives at risk in order to identify those who would benefit from close assessment/monitoring for evidence of genitourinary structural or functional defects, MODY5, and developmental delays / intellectual disability.

Genetic counseling.

17q12 recurrent deletion syndrome is inherited in an autosomal dominant manner, with approximately 75% of deletions occurring de novo and approximately 25% inherited from a parent. Each child of an individual with 17q12 recurrent deletion syndrome has a 50% chance of inheriting the deletion. Once the 17q12 recurrent deletion has been identified in an affected family member, prenatal and preimplantation genetic testing for 17q12 recurrent deletion syndrome are possible.

Diagnosis

No consensus clinical diagnostic criteria for 17q12 recurrent deletion syndrome have been published.

Suggestive Findings

17q12 recurrent deletion syndrome should be suspected in individuals with any of the following clinical, laboratory, and family history findings.

Clinical findings

Kidney abnormalities
- Congenital abnormalities of the kidney and urinary tract (CAKUT), including (1) abnormalities on prenatal imaging (e.g., hyperechogenicity or poor corticomedullary differentiation); (2) abnormalities of kidney parenchyma (e.g., hypoplasia, dysplasia, multicystic dysplastic kidney, or agenesis); (3) fusion anomalies (e.g., horseshoe kidney); (4) collecting system abnormalities (e.g., duplicated collecting systems, ureteropelvic junction obstruction, isolated hydronephrosis, or hydroureter)
- Tubulointerstitial disease, characterized by reduced urine-concentrating ability with bland urinary sediment, absent-to-minimal albuminuria/proteinuria, hyperuricemia, hypomagnesemia, hypokalemia, and tubulointerstitial fibrosis on kidney histology. In some instances, hypomagnesemia is the initial and predominant symptom of kidney disease [van der Made et al 2015].
Neurodevelopmental or neuropsychiatric disorders (e.g., developmental delay, intellectual disability, autism spectrum disorder, attention-deficit/hyperactivity disorder, schizophrenia, anxiety, and bipolar disorder)
Maturity-onset diabetes of the young (MODY), a type of monogenic diabetes resulting from beta-cell dysfunction
Müllerian aplasia / Mayer-Rokitansky-Küster-Hauser syndrome in females

Laboratory findings. Whole-gene deletion of HNF1B identified on gene-targeted deletion/duplication analysis (i.e., testing that detects deletion of HNF1B but cannot reliably detect the recurrent 17q12 deletion), as virtually all HNF1B whole-gene deletions have been found to be due to a 17q12 recurrent deletion [Laffargue et al 2015].

Note: Identification of an intragenic HNF1B pathogenic variant on sequence analysis establishes the diagnosis of an HNF1B-related disorder (see Genetically Related Disorders) and excludes the diagnosis of 17q12 recurrent deletion syndrome.

Family history is consistent with autosomal dominant inheritance (e.g., affected males and females in multiple generations). Absence of a known family history does not preclude the diagnosis.

Establishing the Diagnosis

The diagnosis of 17q12 recurrent deletion syndrome is established in a proband by the presence of a heterozygous recurrent 1.4-Mb deletion at the approximate position of 36,458,167-37,854,616 in the reference genome (NCBI Genome Data Viewer) (see Table 1).

Note: (1) For the purposes of this chapter, the term "17q12 recurrent deletion" is defined as heterozygous and by the genomic coordinates provided in Table 1; it does not denote deletions outside of this region or biallelic deletions. (2) The phenotype of significantly larger or smaller heterozygous deletions within this region and of biallelic recurrent 17q12 deletions may be clinically distinct from the heterozygous recurrent 17q12 deletion (see Genetically Related Disorders).

Although several genes of interest are within the 1.4-Mb deletion, no single gene has been identified to be causative of the overall phenotype of this recurrent deletion syndrome (see Molecular Genetics for genes of interest in the deleted region).

Genomic testing methods that determine the copy number of sequences can include chromosomal microarray (CMA), exome sequencing with copy number variant (CNV) calling, genome sequencing, or targeted deletion analysis. Note: The 17q12 recurrent deletion cannot be identified by routine analysis of G-banded chromosomes or other conventional cytogenetic banding techniques.

CMA using oligonucleotide arrays or SNP genotyping arrays can detect the recurrent deletion in a proband. The ability to size the deletion depends on the type of microarray used and the density of probes in the 17q12 region.
Note: (1) Most individuals with the 17q12 recurrent deletion are identified by CMA performed in the context of evaluation for developmental delay, intellectual disability, or autism spectrum disorder. (2) Prior to 2007, many CMA platforms did not include coverage for this region and thus may not have detected this deletion.
Exome and genome sequencing analyses are next-generation sequencing technologies that generate DNA sequence either for all coding regions (exome) or the entire genome. CNV-calling algorithms need to be utilized to detect the 17q12 recurrent deletion.
Targeted deletion testing. FISH analysis, quantitative PCR, and MLPA may be used to test at-risk relatives of a proband known to have the 17q12 recurrent deletion. Note: (1) Targeted deletion testing is not appropriate for an individual in whom the 17q12 recurrent deletion was not detected by CMA designed to target this region. (2) It is not possible to size the deletion routinely by use of targeted methods.

Table 1.

Genomic Testing Used in 17q12 Recurrent Deletion Syndrome

Deletion ¹	ClinGen ID ²	Region Location ^3, 4	Method	Sensitivity
Deletion ¹	ClinGen ID ²	Region Location ^3, 4	Method	Proband	At-risk family members
1.4-Mb heterozygous recurrent deletion at 17q12	ISCA-37432	GRCh38/hg38 chr17:36,458,167-37,854,616del	CMA ⁵	100%	100%
			Exome & genome sequencing ⁶	100%	100%
			Targeted deletion analysis ⁷	NA ⁸	100% ⁹

: NA = not applicable
1.: See Molecular Genetics for details of the deletion.
2.: Standardized clinical annotation and interpretation for genomic variants from the Clinical Genome Resource (ClinGen) project, formerly the International Standards for Cytogenomic Arrays (ISCA) Consortium. ClinGen still identifies chromosome anomalies by their original ISCA ID number.
3.: Genomic coordinates represent the minimum deletion size associated with the 17q12 recurrent deletion as designated by ClinGen. Deletion coordinates may vary slightly based on array design used by the testing laboratory. Note that the size of the deletion as calculated from these genomic positions may differ from the expected deletion size due to the presence of segmental duplications near breakpoints. The phenotype of significantly larger or smaller deletions within this region may be clinically distinct from the recurrent 17q12 deletion (see Genetically Related Disorders).
4.: See Molecular Genetics for genes of interest included in the deleted region.
5.: CMA using oligonucleotide arrays or SNP genotyping arrays. CMA designs in current clinical use target the 17q12 region. Note: The 17q12 recurrent deletion may not have been detectable by older oligonucleotide or BAC platforms.
6.: CNV-calling algorithms need to be utilized to detect the 17q12 recurrent deletion.
7.: Targeted deletion analysis methods can include FISH, quantitative PCR (qPCR), and multiplex ligation-dependent probe amplification (MLPA), as well as other targeted quantitative methods.
8.: Targeted deletion analysis is not appropriate for an individual in whom the 17q12 recurrent deletion was not detected by CMA designed to target this region.
9.: Targeted deletion analysis may be used to test at-risk relatives of a proband known to have the 17q12 recurrent deletion.

Clinical Characteristics

Clinical Description

17q12 recurrent deletion syndrome is characterized by variable combinations of the following three most common findings: kidney abnormalities – including congenital abnormalities of the kidney and urinary tract (CAKUT) and tubulointerstitial disease – maturity-onset diabetes of the young (MODY), and neurodevelopmental/neuropsychiatric disorders (e.g., developmental delay, intellectual disability, autism spectrum disorder [ASD], attention-deficit/hyperactivity disorder [ADHD], schizophrenia, anxiety, and bipolar disorder). In families with more than one affected individual, significant intrafamilial variability has been reported.

To calculate the frequency rates for these features reported in 17q12 recurrent deletion syndrome, the authors reviewed phenotypic information for 282 individuals on whom sufficiently detailed phenotypic information was reported in 42 studies (see Table 2) using the following criteria:

To minimize ascertainment bias, studies involving disease-specific cohorts were not included in the prevalence calculations of that particular phenotypic manifestation (e.g., kidney anomalies).
Individuals with HNF1B pathogenic sequence variants were not included; however, individuals with whole-gene HNF1B deletions were included, as virtually all whole-gene deletions have been found to be due to a 17q12 recurrent deletion [Laffargue et al 2015].

Table 2.

17q12 Recurrent Deletion Syndrome: Frequency of Select Features

Frequency	Features
Most common (>50%)	Kidney structural or functional defects Neurodevelopmental/neuropsychiatric disorders Mild dysmorphic features
Common (25%-50%)	Maturity-onset diabetes of the young type 5 Female & male genital abnormalities Structural & functional liver abnormalities Hyperparathyroidism Eye abnormalities Structural & exocrine abnormalities of the pancreas Prematurity Nonspecific structural brain findings
Less common (<25%)	Congenital cardiac anomalies Musculoskeletal features Other gastrointestinal features Seizures

: Clinical data summarized from 42 studies, including 282 individuals in whom the 17q12 recurrent deletion was identified [Bellanné-Chantelot et al 2005, Faguer et al 2007, Mefford et al 2007, Cheroki et al 2008, Edghill et al 2008, Bernardini et al 2009, Raile et al 2009, Loirat et al 2010, Moreno-De-Luca et al 2010, Nagamani et al 2010, Oram et al 2010, Kasperavičiūtė et al 2011, Nik-Zainal et al 2011, Dixit et al 2012, George et al 2012, Grozeva et al 2012, Hendrix et al 2012, Hinkes et al 2012, Sanna-Cherchi et al 2012, Ferrè et al 2013, Palumbo et al 2014, Quintero-Rivera et al 2014, Roberts et al 2014, Stefansson et al 2014, Goumy et al 2015, Laffargue et al 2015, Verbitsky et al 2015, Rasmussen et al 2016, Dubois-Laforgue et al 2017a, Madariaga et al 2018, Roehlen et al 2018, Stiles et al 2018, Dotto et al 2019, Li et al 2019, Okorn et al 2019, Vasileiou et al 2019, Bustamante et al 2020, Du et al 2020, Kołbuc et al 2020, Lim et al 2020, Sztromwasser et al 2020, Berberich et al 2021, Cleper et al 2021, Milone et al 2021, Motyka et al 2021, Cheng et al 2022, Thewjitcharoen et al 2022, Kumar et al 2023, Oh et al 2023, Xin & Zhang 2023, Chen et al 2024, Hasegawa et al 2024, Kołbuc et al 2024, Lee et al 2024, Song et al 2024, Verscaj et al 2024]

Most Common Features (>50%)

Kidney disease. Structural kidney abnormalities and unspecified chronic kidney disease have been described in 294 individuals. Cystic dysplastic kidneys and other structural kidney anomalies are reported in 167/193 (87%) individuals who were not ascertained through cohorts with kidney disease, making this feature the most commonly reported manifestation of 17q12 recurrent deletion syndrome.

Cystic dysplasia is the most common kidney finding; other structural kidney and urinary tract abnormalities include poor corticomedullary differentiation, collecting system abnormalities (duplicated collecting system, hydronephrosis, pyelectasis, vesicoureteral reflux, dilated ureter), single kidney (due to unilateral agenesis or involution of a cystic dysplastic kidney), and horseshoe kidney. Prenatal imaging most often shows kidney cysts or echogenic kidneys, but in many individuals (35%) findings may not develop until childhood or later [Verscaj et al 2024].

Individuals may also present with tubulointerstitial disease, which is characterized by reduced urine-concentrating ability, bland urinary sediment, absent-to-minimal albuminuria/proteinuria, hyperuricemia, hypomagnesemia, hypokalemia, and slowly progressive kidney disease; interstitial fibrosis and tubular atrophy are seen on biopsy (although biopsy is not routinely indicated) [Eckardt et al 2015, Verhave et al 2016]. Of note, autosomal dominant tubulointerstitial kidney disease (ADTKD) caused by HNF1B haploinsufficiency (frequently due to 17q12 deletion) is designated ADTKD-HNF1B [Eckardt et al 2015].

Renal tubular wasting of magnesium resulting in hypomagnesemia is common and can be the initial and predominant manifestation of kidney disease in individuals with HNF1B haploinsufficiency, including those with the 17q12 recurrent deletion [Clissold et al 2015, Raaijmakers et al 2015, van der Made et al 2015]. Hypomagnesemia is reported in 46/107 (43%) individuals with 17q12 recurrent deletion and can be severe [Ferrè et al 2013, Madariaga et al 2018, Dotto et al 2019, Li et al 2019, Okorn et al 2019, Berberich et al 2021, Cleper et al 2021, Motyka et al 2021, Cheng et al 2022, Thewjitcharoen et al 2022, Xin & Zhang 2023, Hasegawa et al 2024, Lee et al 2024, Verscaj et al 2024]. Some studies suggest that hypomagnesemia may be underdiagnosed among children with HNF1B-related disorders, including 17q12 recurrent deletion, and may be present in as many as 59% when using age-appropriate norms for children [Kołbuc et al 2024]. In adults, renal tubular magnesium wasting can be diagnosed through an elevated fractional excretion of magnesium (FEMg >2%) in individuals with normal kidney function.

The spectrum of severity and range in age of detection of HNF1B-associated kidney disease are broad, including prenatal severe kidney failure, slow progression to end-stage kidney disease (ESKD) in adulthood, and normal kidney function never requiring kidney replacement therapy [Madariaga et al 2013, Clissold et al 2015, Verhave et al 2016]. While initial evidence suggested that the cause of HNF1B haploinsufficiency – 17q12 deletion, an HNF1B missense variant, or an HNF1B truncating variant (nonsense, frameshift, or splice site) – did not predict the type and severity of kidney involvement [Raaijmakers et al 2015], more recent evidence indicates that intragenic HNF1B pathogenic variants may be associated with worse kidney function and higher risk of progression to ESKD compared to 17q12 deletions [Dubois-Laforgue et al 2017b, Clissold et al 2018, Buffin-Meyer et al 2024]. The reason for this finding is unknown, but the authors speculate a possible dominant-negative effect of certain HNF1B variants resulting in a more severe phenotype, or a protective effect conferred by the loss of one or more genes in the 17q12 recurrent deletion region.

Progression to ESKD in childhood appears to be uncommon among individuals with HNF1B haploinsufficiency, including those with the 17q12 recurrent deletion [Bockenhauer & Jaureguiberry 2016]. In a large retrospective cohort study, progression to ESKD was less common among adults with 17q12 deletion at follow up (51%) compared to those with HNF1B intragenic pathogenic variants (78%) [Dubois-Laforgue et al 2017b].

Neurodevelopmental/neuropsychiatric disorders. Deletions in 17q12 increase the risk of developing diverse neurodevelopmental or neuropsychiatric conditions. The studies that support these observations have taken complementary approaches, including (1) studying the different genetic findings identified in people with the same clinical diagnoses (phenotype first), and (2) studying the clinical features that occur in people who all share the same genetic cause (genotype first).

A recent large phenotype-first population study has established that, out of all recurrent deletions studied, deletions in 17q12 have the strongest association with ASD (hazard ratio [HR] 7.79, 95% CI 2.71-22.43) and ADHD (HR 4.24, 95% CI 1.29-13.92), and show a very strong trend toward increasing the chances of developing schizophrenia spectrum disorders (HR 4.84, 95% CI 0.81-28.85) [Vaez et al 2024]. This study has multiple strengths, including estimating effect sizes from the general population rather than from participants who are already engaged in the health care system, which could result in a bias toward more severe clinical phenotypes; and including multiple other recurrent copy number variants that help put into context the magnitude of the associations with neuropsychiatric and neurodevelopmental conditions.

Genotype-first studies have shown that ASD and schizophrenia are among the clinical features most strongly associated with 17q12 deletions and can be observed more frequently in people with this deletion compared to the general population. While not routinely assessed, ASD or autistic features are described in 13% of individuals ascertained for other clinical findings [Raile et al 2009, Loirat et al 2010, Dixit et al 2012, Palumbo et al 2014, Roberts et al 2014, Goumy et al 2015, Laffargue et al 2015, Rasmussen et al 2016, Li et al 2019, Vasileiou et al 2019, Lim et al 2020, Cleper et al 2021, Verscaj et al 2024]. One study found that 14/110 (13%) children with 17q12 recurrent deletion syndrome required special school placement, which the researchers used as a proxy for severe neuropsychiatric disorder [Laliève et al 2020]. In addition, global developmental delay, intellectual disability, ADHD, and bipolar disorder have been described in individuals with 17q12 deletions [Moreno-De-Luca et al 2010, Laliève et al 2020].

Moreover, speech and motor delay are common findings, reported in 56% and 64% of individuals, respectively. Overall, about half (41/89) of individuals with 17q12 recurrent deletion syndrome are reported to have some degree of learning disability, although phenotypic information about cognitive skills was limited in most studies. Learning difficulties, when noted, are most often described as mild.

Some studies suggest that genes other than HNF1B in the 17q12 region could be responsible for neurodevelopmental and neuropsychiatric features, although evidence is mixed. One study found that individuals with the recurrent 17q12 deletion, not an HNF1B intragenic pathogenic variant, exhibited neurodevelopmental disorders, psychopathology, and autistic traits [Clissold et al 2016]; however, other studies have found that both groups of HNF1B-related disorders are associated with an increased risk of intellectual disability [Dubois-Laforgue et al 2017a, Laliève et al 2020]. These findings were summarized in a recent review, where neurodevelopmental disorders seem to occur in about 25% of individuals with a recurrent 17q12 deletion, and in 6.8% of those with an HNF1B intragenic variant [Nittel et al 2023]. While haploinsufficiency of HNF1B alone may not be sufficient to result in the cognitive and behavioral features associated with the 17q12 recurrent deletion, HNF1B appears to contribute in part to the risk for neurodevelopmental disorders conferred by 17q12 deletion.

Dysmorphic features. Subtle but highly variable dysmorphic features are described for most individuals for whom this information is available. The most commonly described features include high forehead, frontal bossing, depressed nasal bridge, deep-set eyes, full cheeks, downslanted palpebral fissures, high palate, and high-arched eyebrows [Moreno-De-Luca et al 2010, Laffargue et al 2015, Rasmussen et al 2016, Roehlen et al 2018, Vasileiou et al 2019].

Hypoplastic nails and 2-3 finger/toe syndactyly are also frequently reported [Moreno-De-Luca et al 2010, Kasperavičiūtė et al 2011, Palumbo et al 2014].

Common Features (25%-50%)

Maturity-onset diabetes of the young type 5 (MODY5) is most often diagnosed before age 25 years (range: 10-50 years) [Bellanné-Chantelot et al 2005].

Overt diabetes mellitus and abnormal blood glucose levels and/or insulin response are reported in 58/155 (37%) individuals with 17q12 recurrent deletion syndrome not ascertained from cohorts with diabetes mellitus; however, this is almost certainly an underestimate of the lifetime prevalence, since many individuals described in the literature are children and young adults who may not yet have developed manifestations of diabetes. When cohorts with diabetes mellitus are considered, prevalence of MODY5 among individuals with 17q12 recurrent deletion syndrome is 50%.

While many individuals with 17q12 recurrent deletion syndrome with MODY5 have some residual insulin secretion at the time of diagnosis, one study found that 79% required insulin therapy by ten-year follow up [Dubois-Laforgue et al 2017b].

Genital abnormalities. About one third of females and one quarter of males have genital abnormalities.

In females, the most commonly reported finding is partial or complete absence of the upper part of the vagina, cervix, and uterus, often referred to as müllerian aplasia or Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome [Bernardini et al 2009]. Other reported uterine abnormalities include bicornuate uterus, uterus didelphys, hypoplastic uterus, and ovarian cysts [Oram et al 2010, Stiles et al 2018, Vasileiou et al 2019, Kumar et al 2023, Lee et al 2024, Song et al 2024].

In males, genital abnormalities include cryptorchidism, shawl scrotum, phimosis, urethral stenosis or obstruction, hypospadias, epididymal cysts, prostate cyst, and enlarged scrotum [Nagamani et al 2010, Madariaga et al 2018, Lim et al 2020, Xin & Zhang 2023, Hasegawa et al 2024, Verscaj et al 2024].

Structural and functional abnormalities of the liver. Elevated liver enzymes and/or structural abnormalities were reported in 74/171 (43%) individuals in cohorts ascertained for kidney involvement, diabetes mellitus, and uterine malformations [Rasmussen et al 2016, Dubois-Laforgue et al 2017a, Okorn et al 2019]. Liver involvement ranges from asymptomatic elevation of hepatic transaminase enzyme levels to adult-onset cholestasis [Kotalova et al 2015, Pinon et al 2019]. Neonatal cholestasis with paucity of interlobular bile ducts and variable periportal fibrosis has also been reported in several infants with 17q12 recurrent deletion syndrome, including one who required portoenterostomy and one who developed hepatocellular carcinoma requiring liver transplantation [Pinon et al 2019]. Additional reported liver abnormalities include choledochal and common bile duct cysts, hepatomegaly, steatohepatitis, and hypoplasia with portal vein thrombosis [Roehlen et al 2018, Lim et al 2020, Lee et al 2024]. One study reported an even higher frequency of abnormal liver function tests (71%) in a large cohort that included both intragenic HNF1B variants and 17q12 deletions [Dubois-Laforgue et al 2017b]. While the study's authors did not differentiate between genotypes, no statistically significant genotype-phenotype correlations were reported, suggesting that elevated liver function tests may be even more common (>50%).

Hyperparathyroidism. Twenty of 45 (44%) individuals who had parathyroid hormone (PTH) plasma levels tested were found to have hyperparathyroidism [Ferrè et al 2013, Li et al 2019, Kołbuc et al 2020, Lim et al 2020, Berberich et al 2021, Cleper et al 2021]. Furthermore, one study reported transient neonatal hypercalcemia and hypophosphatemia, the combination of which is suggestive of hyperparathyroidism, although PTH levels were not specifically measured to confirm [Dixit et al 2012]. Another study demonstrated that HNF1B (hepatocyte nuclear factor 1-beta, encoded by HNF1B) is expressed in the parathyroid gland and acts as a transcriptional repressor of PTH [Ferrè et al 2013]. Additionally, this study found that PTH levels remained increased even after kidney transplantation and normalized magnesium levels in some individuals. Although hyperparathyroidism is persistent in 20%-50% of individuals following kidney transplant regardless of the cause of kidney disease, the authors concluded that the weight of the evidence suggests that HNF1B haploinsufficiency causes hyperparathyroidism independent of associated kidney failure.

Eye abnormalities. Twenty-four of 66 (36%) reported individuals had eye findings that included strabismus [Vasileiou et al 2019, Kumar et al 2023, Verscaj et al 2024], esotropia [Milone et al 2021, Verscaj et al 2024], nystagmus [Cheroki et al 2008, Milone et al 2021], posterior embryotoxon [Dixit et al 2012], hypermetropia [Moreno-De-Luca et al 2010, Verscaj et al 2024], high myopia [Milone et al 2021], cataracts [Nagamani et al 2010, Oh et al 2023, Verscaj et al 2024], coloboma [Raile et al 2009], parapapillary dystrophy [Milone et al 2021], Purtcher-like retinopathy [Oh et al 2023], diabetic retinopathy [Lee et al 2024], and keratoconus requiring corneal transplant [Hasegawa et al 2024].

Structural and exocrine abnormalities of the pancreas. About one third (39/113) of individuals with imaging results were found to have some morphologic abnormality of the pancreas, most often hypoplasia, atrophy, and/or agenesis of the body and tail [Madariaga et al 2018, Roehlen et al 2018, Dotto et al 2019, Kołbuc et al 2020, Motyka et al 2021, Kumar et al 2023, Thewjitcharoen et al 2022, Xin & Zhang 2023, Hasegawa et al 2024, Lee et al 2024, Song et al 2024]. Two studies identified exocrine pancreatic insufficiency (EPI), defined as fecal elastase-1 level <200 µg/g, in 37/67 (55%) of individuals with either 17q12 deletion or HNF1B pathogenic variant [Dubois-Laforgue et al 2017b, Clissold et al 2018]. These publications did not provide case-level data sufficient to allow calculation of the frequency of EPI among those with a deletion specifically, although Dubois-Laforgue et al [2017b] reported no significant genotype-phenotype correlations for this feature. Several small studies reported EPI in 2/9 (22%) individuals with the 17q12 deletion [Raile et al 2009, Quintero-Rivera et al 2014, Roehlen et al 2018]. Structural anomalies of the pancreas and EPI occur more commonly, but not exclusively, when diabetes mellitus is present.

Prematurity. Among 20 studies that reported gestational age in infants with 17q12 recurrent deletion syndrome, 16/55 individuals (29%) were born prematurely (<37 weeks).

Nonspecific structural brain findings. No systematic neuroimaging studies of cohorts with 17q12 recurrent deletion syndrome have been published. Among publications describing neuroimaging findings, structural brain anomalies were reported in 10/37 (27%) individuals. These abnormalities, which appeared to be nonspecific and to vary widely, include the following:

Ventricular dilatation with and without diffuse brain atrophy [Vasileiou et al 2019, Lee et al 2024]
Mild cerebellar atrophy [Kasperavičiūtė et al 2011]
White matter abnormality [Moreno-De-Luca et al 2010, Milone et al 2021]
Atrophy of the hippocampus [Nagamani et al 2010]

Less Common Features (<25%)

Congenital heart anomalies are reported in 10/52 (19%) individuals, ranging from mild to severe. Cardiac anomalies include right heart failure with tricuspid valve insufficiency, increased aortic root size, aortic insufficiency, coarctation of the aorta, bicuspid aortic valve, ventricular septal defect, transposition of the great arteries, pulmonary valve defect, tricuspid regurgitation, patent ductus arteriosus, patent foramen ovale, and mitral valve prolapse [Hinkes et al 2012, Palumbo et al 2014, Roberts et al 2014, Vasileiou et al 2019, Du et al 2020, Cleper et al 2021, Verscaj et al 2024].

Musculoskeletal. Eleven of 47 (23%) individuals were reported to have short stature. Other musculoskeletal differences include joint laxity (8 persons), long/slender hands and feet (4), pectus deformity (3), fifth finger clinodactyly (3), single transverse palmar crease (1), and hip dysplasia (1).

Other gastrointestinal features. Gastroesophageal reflux disease was reported in four individuals [Moreno-De-Luca et al 2010, Goumy et al 2015, Rasmussen et al 2016, Cheng et al 2022]. Congenital diaphragmatic hernia was reported in two individuals. Two individuals had duodenal atresia [Quintero-Rivera et al 2014, Verscaj et al 2024] and two had esophageal abnormalities, including hiatal hernia caused by a short esophagus and dysphagia [Rasmussen et al 2016]. There has been one report of gastroparesis [Xin & Zhang 2023].

Seizures. Ten of 84 individuals (12%) had seizure activity, including febrile seizures [Moreno-De-Luca et al 2010], partial complex seizures [Nagamani et al 2010], tonic-clonic seizures [Cleper et al 2021], and mesial temporal lobe epilepsy requiring lobectomy [Kasperavičiūtė et al 2011].

Other

Hypotonia (6 persons)
Macrocephaly (6)
Prenatal oligohydramnios (4)
Sensorineural hearing loss (4)
Deep vein thrombosis / vascular calcifications (2)
Ovarian carcinoma (1)
Dyslipidemia (1)

Penetrance

17q12 recurrent deletion syndrome is highly penetrant. Although it is inherited about 25% of the time, there have been no clear reports of unaffected parents with 17q12 recurrent deletion syndrome.

Prevalence

The reported prevalence of 17q12 recurrent deletion syndrome in a large, unbiased population not selected on the basis of disease was 1:6,250 [Vaez et al 2024]. However, other estimates range from 1:4,000 in a relatively small population-based pregnancy cohort [Smajlagić et al 2021] to 1:50,000 in healthy European volunteers [Crawford et al 2019].

Genetically Related Disorders

Intragenic HNF1B pathogenic variants. The clinical findings of HNF1B heterozygous pathogenic variants alone (without involvement of adjacent genes) can include both HNF1B-related kidney disease and extrarenal involvement. HNF1B-related kidney disease comprises – in varying combinations – (1) congenital anomalies of the kidney and urinary tract (e.g., hyperechogenic kidneys, kidney cysts, structural abnormalities) [Clissold et al 2015], (2) autosomal dominant tubulointerstitial kidney disease (ADTKD-HNF1B) [Bleyer et al 2022], and (3) hypomagnesemia. Extra-kidney phenotypes are common and include pancreatic atrophy, maturity-onset diabetes of the young type 5 (MODY5, or renal cysts and diabetes [RCAD] syndrome), and a spectrum of hepatic involvement (see Pediatric Genetic Cholestatic Liver Disease Overview).

Intragenic HNF1B pathogenic variants may be associated with worse kidney function and higher risk of progression to end-stage kidney disease compared to 17q12 recurrent deletions [Dubois-Laforgue et al 2017b, Clissold et al 2018, Buffin-Meyer et al 2024] and are less likely to be associated with neurodevelopmental disorders [Nittel et al 2023].

Contiguous gene deletions. The phenotype of significantly larger or smaller deletions within this region may be clinically distinct from 17q12 recurrent deletion syndrome.

17q12 recurrent duplication is characterized by intellectual abilities ranging from normal to severe disability and other variable clinical manifestations. Speech delay is common, and most affected individuals have some degree of hypotonia and gross motor delay. Behavioral and psychiatric conditions reported in some affected individuals include autism spectrum disorder, schizophrenia, and behavioral abnormalities (aggression and self-injury). Seizures are present in 75%. The 17q12 recurrent duplication encompasses the same genes as the 17q12 recurrent deletion. Although there are several genes of interest (e.g., ACACA, LHX1, and HNF1B) within the 1.4-Mb recurrent duplication, no single gene has been identified as causative of the phenotype. The 17q12 recurrent duplication is inherited in an autosomal dominant manner, with approximately 10% of duplications occurring de novo and approximately 90% inherited from a parent who is often minimally affected or phenotypically normal.

Differential Diagnosis

Kidney structural or functional defects. See Table 3.

Table 3.

Genetic Disorders with Kidney Structural or Functional Defects in the Differential Diagnosis of 17q12 Recurrent Deletion Syndrome

Gene(s)	Disorder	MOI	Kidney-Related Phenotype	Other Features
>20 genes incl: CEP290 INVS IQCB1 NPHP1 NPHP3 NPHP4 TMEM67	Nephronophthisis-related ciliopathies	AR (typically)	Polyuria & polydipsia resulting from ↓ urine-concentrating ability Chronic tubulointerstitial nephritis Progression to ESKD Note: NPH is suspected in absence of CAKUT & signs/symptoms of glomerular kidney disease.	Chronic anemia resistant to therapy Growth restriction Note: NPH may be isolated or part of a syndrome, such as Joubert, Bardet-Biedl, Jeune & related skeletal disorders, Meckel-Gruber, Senior-Loken, Leber congenital amaurosis, or COACH.
ALG5 ALG9 DNAJB11 GANAB IFT140 PKD1 PKD2	Polycystic kidney disease, autosomal dominant	AD	Numerous bilateral cysts Kidney enlargement Early-onset hypertension Nephrolithiasis Acute or chronic abdominal/flank pain Kidney insufficiency ~50% have ESKD by age 60 yrs	Polycystic liver disease Cysts in pancreas, seminal vesicles, & arachnoid membrane ↑ risk of intracranial aneurysms; dilatation of aortic root, & dissection of thoracic aorta; mitral valve prolapse Abdominal wall hernias
ALG8 GANAB ¹ LRP5 PRKCSH SEC63 SEC61B ²	Polycystic liver disease (OMIM PS174050)	AD	Few kidney cysts occasionally reported	Polycystic liver disease
BICC1	Cystic renal dysplasia, susceptibility to (OMIM 601331)	AD	Cystic renal dysplasia VUR	None
BMPER	Diaphanospondylodysostosis, BMPER-related (OMIM 608022)	AR	Nephroblastomatosis w/cystic kidneys	Skeletal anomalies (small chest, abnormal vertebral segmentation, & posterior rib gaps) Craniofacial anomalies (hypertelorism, epicanthal folds, depressed nasal bridge w/short nose, & low-set ears)
CRB2	Ventriculomegaly w/cystic kidney disease (OMIM 219730)	AR	Microscopic renal tubular cysts	Dilated cerebral ventricles Postaxial polydactyly Ventricular septal defect
CYS1 DZIP1L PKD1 PKHD1 ³	Autosomal recessive polycystic kidney disease (See ARPKD-PKHD1.)	AR	Perinatal presentation: Enlarged hyperechogenic kidneys Variable CKD Oligo- or anhydramnios & related lung disease often cause most significant complications. Infantile: Enlarged hyperechogenic kidneys Micro- & macrocysts Variable CKD Age >1 yr: Enlarged kidneys w/multiple macrocysts ↑ echogenicity ↓ cortex-medulla differentiation Possible variable CKD	Perinatal/infantile: Inhomogeneous liver parenchyma due to congenital hepatic fibrosis, hepatomegaly, bile duct dilatation / cystic changes Age >1 yr: Progressive liver fibrosis & portal hypertension; bile duct dilatation Predominance of liver disease in some persons w/only mild functional & structural kidney disease
EYA1 SIX1 SIX5	Branchiootorenal spectrum disorder	AD	Renal agenesis, hypoplasia, or dysplasia Ureteropelvic junction obstruction Calyceal cyst/diverticulum Caliectasis, pelviectasis, hydronephrosis, VUR	Malformations of outer, middle, & inner ear & hearing impairment 2nd branchial arch anomalies (sinus tract, cyst)
JAG1 NOTCH2	Alagille syndrome	AD	Structural involvement: small hyperechoic kidney, ureteropelvic obstruction, renal cysts Functional involvement: most commonly renal tubular acidosis	Cholestasis Congenital cardiac defects Butterfly vertebrae Ophthalmologic abnormalities Characteristic facial features
MUC1	Autosomal dominant tubulointerstitial kidney disease – MUC1	AD	Tubulointerstitial disease Few small corticomedullary cysts in 50% Normal or small-sized kidneys CKD w/highly variable progression to ESKD
OFD1	Oral-facial-digital syndrome type I	XL	Polycystic kidneys in females Risk for significant kidney disease appears to be >60% after age 18 yrs	Cleft palate Dental anomalies Facial dysmorphology Digital anomalies ID
PAX2	Renal coloboma syndrome (See PAX2-Related Disorder.)	AD	Hypoplastic, dysplastic, multicystic kidneys Oligomeganephronia Renal insufficiency & ESKD VUR FSGS	Ophthalmologic abnormalities (optic nerve dysplasia, retinal coloboma, other eye malformations)
PMM2	Hyperinsulinemia w/hypoglycemia & polycystic kidney disease ⁴	AR	Antenatal or childhood-onset enlarged hyperechogenic kidneys w/multiple cysts Variable progression of CKD to ESKD from infancy to early adulthood	Infantile hyperinsulinemic hypoglycemia Liver cysts
REN	Autosomal dominant tubulointerstitial kidney disease – REN	AD	Childhood/adolescent-onset: ↓ estimated glomerular filtration rate, acidosis, hyperkalemia, & anemia early in life, followed by slowly progressive CKD & gout Adult onset: gout or mild, slowly progressive CKD beginning in 3rd decade
SEC61A1	Autosomal dominant tubulointerstitial kidney disease – SEC61A1 (OMIM 617056)	AD	Bilateral small cysts in 50% Normal or small-sized kidneys CKD	• IUGR • Congenital anemia
TSC1 TSC2	Tuberous sclerosis complex	AD	Benign renal angiomyolipomas Epithelial cysts Oncocytoma Renal cell carcinoma	Characteristic skin lesions CNS manifestations (e.g., TAND) Cardiac rhabdomyomas, arrhythmias LAM, multifocal micronodular pneumonocyte hyperplasia
UMOD	Autosomal dominant tubulointerstitial kidney disease – UMOD	AD	Normal urinalysis & slowly progressive CKD, usually 1st noted in teen yrs & progressing to ESKD between 3rd & 7th decades Hyperuricemia Gout
VHL	Von Hippel-Lindau syndrome	AD	Bilateral cysts Renal cell carcinoma	Hemangioblastomas of brain, spinal cord, & retina Pheochromocytoma & paraganglioma Pancreatic cysts & neuroendocrine tumors Endolymphatic sac tumors Epididymal & broad ligament cystadenomas

: Adapted from Cornec-Le Gall et al [2019]; Lanktree et al [2019]; Armstrong & Thomas [2019]; Polycystic Kidney Disease, Autosomal Dominant; Polycystic Kidney Disease, Autosomal Recessive; and Nephronophthisis-Related Ciliopathies
: AD = autosomal dominant; ADPKD = autosomal dominant polycystic kidney disease; ADPLD = autosomal dominant polycystic liver disease; ADTKD = autosomal dominant tubulointerstitial kidney disease; AR = autosomal recessive; ARPKD = autosomal recessive polycystic kidney disease; CAKUT = congenital anomalies of the kidney and urinary tract; CKD = chronic kidney disease; CNS = central nervous system; COACH = cerebellar vermis hypo/aplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis; ESKD = end-stage kidney disease; FSGS = focal segmental glomerulonephritis; ID = intellectual disability; IUGR = intrauterine growth restriction; LAM = lymphangioleiomyomatosis; MOI = mode of inheritance; NPH = nephronophthisis; TAND = TSC-associated neuropsychiatric disorder; VUR = vesicoureteral reflux
1.: Porath et al [2016]
2.: Besse et al [2017]
3.: Among individuals with ARPKD, PKHD1 is the most commonly involved gene. Less commonly involved genes include PKD1, CYS1, & DZIP1L. Although the ARPKD phenotype can appear clinically similar regardless of the causative gene, the genetic etiology may be relevant for prognosis of kidney survival (see ARPKD).
4.: Soares et al [2020]

The differential diagnosis of kidney cysts also includes, in children, idiopathic cystic dysplasia and obstructive dysplasia; and, in adults, acquired kidney cysts (related to chronic kidney disease and/or dialysis) or simple cortical cysts [Clissold et al 2015].

Maturity-onset diabetes of the young (MODY) is a group of inherited disorders of non-autoimmune diabetes mellitus that usually present in adolescence or young adulthood (typically age <35 years). MODY is generally inherited in an autosomal dominant manner. To date, it has been proposed that pathogenic variants in at least 14 genes cause MODY. See MODY, Genetic Causes of MODY for associated genes and clinical features. The clinical findings are either:

An atypical type 2 diabetes-like condition that occurs in the absence of the usual predisposing factors (obesity, hypertension, and dyslipidemia) and often without acanthosis nigricans; OR
An atypical type 1 diabetes-like condition that occurs in the absence of the usual clinical and laboratory manifestations (islet cell autoantibodies, persistence of measurable C peptide levels, and diabetic ketoacidosis) [American Diabetes Association 2010, Fajans & Bell 2011, Carroll & Murphy 2013].

Other genetic causes of müllerian aplasia. Five other copy number variants (1q12.1 recurrent deletion, 2q13q14.1 recurrent deletion, 16p11.2 recurrent deletion, and 22q11.2 recurrent deletion and duplication) and pathogenic variants in at least 20 genes outside of the 17q12 region have been identified in two or more individuals with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome / müllerian aplasia [Herlin 2024].

Other genetic causes of neurodevelopmental or neuropsychiatric disorders. The differential diagnosis for developmental delay, intellectual disability, schizophrenia, and autism spectrum disorder includes hundreds of known copy number and single-nucleotide variants and is too broad for discussion here. See OMIM Phenotypic Series for genes associated with the following:

Management

No clinical practice guidelines for 17q12 recurrent deletion syndrome have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with 17q12 recurrent deletion syndrome, the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

17q12 Recurrent Deletion Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern	Evaluation	Comment
Kidney structural or functional defects	Blood pressure Kidney & bladder ultrasound Serum BUN, creatinine, electrolytes (incl calcium, Mg, phosphorus) & uric acid Urine protein, Mg, & creatinine Consultation w/nephrologist	Random urine Mg/creatinine is needed to calculate fractional excretion of Mg. ↑ FEMg (>2%) is diagnostic of tubular Mg wasting in those w/normal kidney function.
Neurodevelopmental/neuropsychiatric disorders	Assessment of speech & language Cognitive, motor, & social development Perceptual anomalies Mood Behavior
MODY5	Fasting glucose & hemoglobin A1c levels Consultation w/endocrinologist
Genital tract abnormalities	Males: clinical exam Females: pelvic ultrasound & gynecologic exam to evaluate for possible müllerian abnormalities
Liver abnormalities	Liver function tests (hepatic function panel, GGT), lipid panel
Hyperparathyroidism	Serum calcium, phosphorus, & intact parathyroid hormone Urine calcium-to-creatinine ratio Consultation w/endocrinologist
Eye abnormalities	Ophthalmologic exam
Exocrine pancreatic insufficiency (EPI)	Measure fecal elastase-1 level to test for EPI in those w/chronic abdominal pain, loose stools, steatorrhea, bloating, excessive flatulence, unintentional weight loss, or poor growth. Also consider fecal elastase-1 measurement in those w/behavior changes who are unable to communicate discomfort effectively.	Although the pancreas is often structurally abnormal on imaging, esp w/a low fecal elastase-1 level, imaging results do not affect treatment or prognosis, & imaging is not routinely recommended when the etiology of EPI is known. ¹
Congenital heart defects	Clinical assessment Consultation w/cardiologist & echocardiography if warranted
Seizures	Neurology consultation if seizures are suspected clinically
Sensorineural hearing loss	Audiologic eval
Genetic counseling	By genetics professionals ²	To obtain a pedigree & inform affected persons & their families re nature, MOI, & implications of 17q12 recurrent deletion syndrome to facilitate medical & personal decision making
Family support & resources	By clinicians, wider care team, & family support organizations	Assessment of family & social structure to determine need for: Community or online resources such as Parent to Parent; Social work involvement for parental support; Home nursing referral; Home psychotherapy or behavioral support.

: BUN = blood urea nitrogen; FEMg = fractional excretion of magnesium; GGT = gamma-glutamyl transferase; Mg = magnesium; MODY5 = maturity-onset diabetes of the young type 5; MOI = mode of inheritance
1.: See Exocrine pancreatic insufficiency in UpToDate^® (accessed 12-12-24).
2.: Clinical geneticist, certified genetic counselor, certified genetic nurse, genetics advanced practice provider (nurse practitioner or physician assistant)

Treatment of Manifestations

Treatment is symptomatic and depends on an individual's specific needs. Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in relevant fields (see Table 5).

Table 5.

17q12 Recurrent Deletion Syndrome: Treatment of Manifestations

Manifestation/ Concern	Treatment	Considerations/Other
Kidney disease	Treatment should follow standard practice. Established guidelines for mgmt of CKD, incl that related to CAKUT or ADTKD, are available for children & adults. ¹ Hypomagnesemia. Oral Mg supplements in organic salt forms (e.g., aspartate, citrate, gluconate) may be more bioavailable than inorganic salt forms (e.g., oxide, sulfate, glycerophosphate). ² Potassium-sparing diuretics & SGLT2 inhibitors may be useful as adjunctive therapy in those w/refractory disease. ³	Some persons have normal kidney function; others may progress to ESKD & require dialysis or kidney transplantation. In those developing ESKD, transplantation is a good option, as kidney disease is not expected to recur. For those who also have diabetes mellitus, simultaneous pancreas & kidney transplantation has been successful & should be considered. ⁴
Neurodevelopmental/ neuropsychiatric disorders	Provide specialized educational instruction, habilitative therapies (e.g., OT, PT, ST), & psychosocial interventions (e.g., behavioral services, social skills instruction) as warranted, beginning in early childhood. Consultation w/subspecialists in developmental/behavioral pediatrics or neurodevelopmental disabilities, child & adolescent psychiatry, &/or pediatric psychology in childhood, depending on the needs of the child. Important roles incl educating families, guiding them to evidence-based interventions & accurate information resources, & helping them navigate the multiple systems of care & transitions that are typically involved in the mgmt of neurodevelopmental disabilities. Psychiatric consultation & therapy for those w/mental health concerns, incl mood & anxiety disorders & psychosis	Intervention involves a multimodal approach to habilitative, educational, social, & emotional needs & assoc impairments, incl behavior problems & coexisting mental health diagnoses. Specific targets of intervention vary w/age, diagnoses, severity, current abilities (e.g., language, cognitive, & functional adaptive skill levels), & family circumstances & preferences. AACAP has published guidelines for assessment & treatment of psychiatric disorders in children & adolescents w/ID. ⁵ Guidelines for mgmt of ASD are available from professional organizations such as AAP, AACAP, & others incl the Lancet Commission. ⁶
MODY5	Treatment should follow standard practice per endocrinologist	There are no published controlled trials of treatment for monogenic diabetes due to 17q12 deletion or HNF1B haploinsufficiency. ⁷ Initial response to oral antihyperglycemic agents appears to be common, ⁸ but overall reports indicate that ~80% used insulin. ⁷
Genital tract abnormalities	Nonsurgical & surgical intervention may be considered for those w/genital tract anomalies, incl müllerian agenesis. All persons w/müllerian agenesis should be offered counseling & encouraged to connect w/peer support groups.	Primary vaginal dilation is successful for >90%-96% of those w/müllerian agenesis. ⁹ Uterus transplantation can restore fertility in women w/uterine agenesis; ¹⁰ gestational surrogacy is an alternative for women desiring genetic motherhood.
Liver abnormalities	Standard treatment(s) as recommended by gastroenterologist	A minority of persons w/neonatal cholestasis have required surgical intervention. ¹¹
Hyperparathyroidism	Standard treatment for hyperparathyroidism ¹²
Eye abnormalities	Standard treatment(s) as recommended by ophthalmologist, incl refractory eye exam & corrective lenses as needed
Exocrine pancreatic insufficiency (EPI)	Pancreatic ERT & lifestyle changes, incl avoiding smoking & drinking alcohol, eating frequent small meals that contain healthy fats, & sometimes taking vitamin supplements	AGA has published clinical guidelines for the diagnosis & mgmt of EPI. ¹³
Congenital heart defects	Medical & surgical mgmt per cardiologist & cardiothoracic surgeon
Seizures	Standardized treatment w/ASMs by experienced neurologist	Many ASMs may be effective (none demonstrated effective specifically for this disorder). Education of parents/caregivers ¹⁴
Sensorineural hearing loss	Hearing aids may be helpful, per audiologist	Community hearing services through early intervention or school district

: AACAP = American Academy of Child and Adolescent Psychiatrists; AAP = American Academy of Pediatrics; ADTKD = autosomal dominant tubulointerstitial kidney disease; AGA = American Gastroenterological Association; ASD = autism spectrum disorder; ASM = anti-seizure medication; CAKUT = congenital anomalies of the kidney and urinary tract; CKD = chronic kidney disease; ERT = enzyme replacement therapy; ESKD = end-stage kidney disease; MODY5 = maturity-onset diabetes of the young type 5; OT = occupational therapy; PT = physical therapy; SGLT2 = sodium-glucose cotransporter 2; ST = speech therapy
1.: Eckardt et al [2015], Stevens et al [2024]
2.: NIH [2018]
3.: Shah et al [2023]
4.: Poitou et al [2012]
5.: Siegel et al [2020]
6.: Volkmar et al [2014], Hyman et al [2020], Lord et al [2022]
7.: Naylor et al [2024]
8.: Dubois-Laforgue et al [2017b]
9.: Committee on Adolescent Health Care [2018]
10.: Brännström et al [2014]
11.: Kotalova et al [2015], Pinon et al [2019]
12.: Bilezikian et al [2022]
13.: Whitcomb et al [2023]
14.: Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see Epilepsy Foundation Toolbox.

Surveillance

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in Table 6 are recommended.

Table 6.

17q12 Recurrent Deletion Syndrome: Recommended Surveillance

System/Concern	Evaluation	Frequency
Kidney structure/function	Kidney & bladder ultrasound to monitor for kidney cysts or other structural abnormalities	In those w/o known structural defects: 12 mos after establishing diagnosis, then every 2-3 yrs in childhood/adolescence & every 3-5 yrs in adulthood If an abnormality is detected, more frequent ultrasound may be warranted.
Kidney structure/function	Monitor: Blood pressure Kidney function Serum concentration of Mg, potassium, uric acid Urine Mg & creatinine Urine protein-to-creatinine ratio	Periodic, preferably under guidance of nephrologist Annual or more frequent monitoring may be advised for those who: (1) have lab findings suggestive of kidney disease; (2) are taking potentially nephrotoxic medications (e.g., NSAIDs); (3) have genitourinary structural abnormalities. ¹
Development / neurobehavioral / psychiatric	Assess developmental progress & educational needs.	At each visit throughout childhood & adolescence
	Assess for features of ASD & ADHD.	At each visit in early childhood
	Full psychoeducational eval incl assessment of speech, cognitive, social/emotional, adaptive, & motor skills	In children who experience difficulty w/school or behavioral challenges
	Assess for prodromal psychotic symptoms & bipolar disorder.	At each visit in adolescence
MODY5	Hemoglobin A1c	Annually
MODY5	Education on clinical signs/symptoms of diabetes mellitus (e.g., polyuria, polydipsia, weight loss [sometimes w/polyphagia], fatigue, nausea, vomiting, blurred vision)	At each visit for all affected persons & parents/caregivers to promote early diagnosis & treatment
Genital tract abnormalities	Consider reevaluation for uterine & vaginal abnormalities related to müllerian duct aplasia. Note: Rudimentary müllerian structures are commonly found on MRI. On ultrasound, these rudimentary structures are difficult to interpret & may be particularly misleading before puberty. ²	In pubertal females w/primary amenorrhea
Liver abnormalities	Hepatic function panel (or comprehensive metabolic panel) & GGT Consider lipid panel given case reports of hepatic steatosis. US may be indicated if labs are abnormal.	Periodic Consider annually w/kidney function tests & electrolytes as described above.
Hyperparathyroidism	Serum calcium & phosphorus	Annually
Eyes	Ophthalmologic eval	Annually during early childhood
Exocrine pancreatic insufficiency (EPI)	Fecal elastase-1 level to assess for EPI in persons w/chronic abdominal pain, loose stools, steatorrhea, bloating, excessive flatulence, unintentional weight loss, or poor growth Also consider fecal elastase-1 measurement in persons w/behavior changes who are unable to communicate discomfort effectively.	As warranted based on signs & symptoms
Neurology	Monitor those w/seizures as clinically indicated.	At each visit
Hearing	Hearing screening	Throughout childhood, per established guidelines of Bright Futures / American Academy of Pediatrics ³

: ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder; GGT = gamma-glutamyl transferase; Mg = magnesium; MODY5 = maturity-onset diabetes of the young type 5; NSAIDs = nonsteroidal anti-inflammatory drugs
1.: Verbitsky et al [2015]
2.: Committee on Adolescent Health Care [2018]
3.: Hagan et al [2017]

Agents/Circumstances to Avoid

Individuals with HNF1B-associated kidney disease (including the 17q12 recurrent deletion) who develop end-stage kidney disease (ESKD) and require kidney transplantation are at increased risk for developing post-transplant diabetes mellitus; therefore, use of an immunosuppressive regimen that avoids tacrolimus and mammalian target of rapamycin (mTOR) inhibitors and reduces corticosteroid exposure may be beneficial, including for those who do not have preexisting diabetes [Zuber et al 2009, Faguer et al 2011, Clissold et al 2015].

Nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs) should be avoided by those with kidney abnormalities. Hepatotoxic medications and alcohol should be avoided by those with liver abnormalities.

For individuals with mental health conditions such as autism spectrum disorder, schizophrenia, or bipolar disorder, the authors recommend caution when considering the use of antipsychotic agents that may lead to weight gain and increased risk of metabolic syndrome and diabetes mellitus, since individuals with 17q12 deletions are already at increased risk for diabetes mellitus. Likewise, the use of mood stabilizers that can affect kidney function in the long term, such as lithium, should be carefully considered in the setting of potential underlying anatomic and functional abnormalities in individuals with 17q12 deletions. These recommendations stem from empirically grounded clinical reasoning based on the underlying phenotypes associated with 17q12 deletions, as large studies assessing the efficacy of these interventions have not yet been performed.

Evaluation of Relatives at Risk

If the 17q12 recurrent deletion is identified in one of the proband's parents on targeted deletion analysis,* it is appropriate to clarify the genetic status of older and younger sibs of the proband and other relatives at risk in order to identify those who would benefit from close assessment/monitoring for evidence of kidney structural or functional defects, maturity-onset diabetes of the young, and developmental delays / intellectual disability.

* FISH analysis, quantitative PCR (qPCR), multiplex ligation-dependent probe amplification (MLPA), or other targeted quantitative methods may be used to test relatives of a proband who is known to have the 17q12 recurrent deletion. Virtually all whole-gene deletions of HNF1B identified by gene-targeted deletion/duplication analysis have been shown to include the entire 17q12 recurrent deletion region [Laffargue et al 2015], which can be confirmed using CMA.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members; it is not meant to address all personal, cultural, or ethical issues that may arise or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

17q12 recurrent deletion syndrome is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

Most studies examining the 17q12 recurrent deletion have not reported whether the parents were tested; therefore, inheritance status is often unknown or the data are limited. However, in 109 individuals with the 17q12 deletion from 26 studies for which this information is available, the deletion was de novo in 82 individuals (75%) and inherited in 27 (25%).
In reported families with parent-to-child transmission of the 17q12 recurrent deletion, significant intrafamilial variability has been observed in clinical manifestations [Moreno-De-Luca et al 2010, George et al 2012, Quintero-Rivera et al 2014, Dotto et al 2019, Okorn et al 2019, Kołbuc et al 2020].
Genomic testing that will detect the 17q12 recurrent deletion present in the proband is recommended for the parents of the proband to evaluate their genetic status, inform recurrence risk assessment, and assess their risk of kidney structural or functional defects, maturity-onset diabetes of the young, and other features associated with the 17q12 recurrent deletion. Because features range in severity, it is possible for parents who are mildly affected to be unaware of any clinical manifestations (diabetes and kidney problems may not be evident until adulthood).
If the 17q12 recurrent deletion identified in the proband is not identified in either parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:
- The proband has a de novo deletion.
- The proband inherited a deletion from a parent with gonadal (or somatic and gonadal) mosaicism. Note: Testing of parental leukocyte DNA may not detect all instances of somatic mosaicism and will not detect a deletion that is present in the germ (gonadal) cells only.

Sibs of a proband. The risk to the sibs of the proband depends on the genetic status of the parents:

If one of the parents has the 17q12 recurrent deletion, the risk to each sib of inheriting the deletion is 50%. However, it is not possible to reliably predict the full phenotypic expression in a sib who inherits the deletion because significant intrafamilial variability may be observed.
If the 17q12 recurrent deletion identified in the proband is not identified in a parent, the recurrence risk to sibs is low (<1%) but greater than that of the general population because of the possibility of parental gonadal mosaicism.

Offspring of a proband. Each child of an individual with 17q12 recurrent deletion syndrome has a 50% chance of inheriting the deletion.

Other family members. The risk to other family members depends on the genetic status of the proband's parent: if a parent has the 17q12 recurrent deletion, the parent's family members may also have the deletion.

Related Genetic Counseling Issues

See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.

Family planning

The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.
It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who have or are at risk of having a child with 17q12 recurrent deletion syndrome.

Prenatal Testing and Preimplantation Genetic Testing

Pregnancies known to be at increased risk for 17q12 recurrent deletion syndrome. Once the 17q12 recurrent deletion has been identified in an affected family member, prenatal and preimplantation genetic testing for 17q12 recurrent deletion syndrome are possible.

Pregnancies not known to be at increased risk for 17q12 recurrent deletion syndrome. Prenatal CMA performed due to indications other than a positive family history (e.g., fetal kidney anomalies detected on ultrasound examination) may detect the 17q12 recurrent deletion [Wapner et al 2012, Wan et al 2019, Zhang et al 2024]. There is a high correlation between fetal hyperechogenic kidneys and the 17q12 recurrent deletion [Jing et al 2019, Huang et al 2024, Verscaj et al 2024], prompting several authors to recommend genetic testing for the 17q12 recurrent deletion when hyperechogenic kidneys of unknown cause are detected prenatally [Jones et al 2015, Jing et al 2019].

Note: Regardless of whether the pregnancy is known or not known to be at increased risk for 17q12 recurrent deletion syndrome, prenatal test results cannot reliably predict the phenotype.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal and preimplantation genetic testing. While most health care professionals would consider use of prenatal and preimplantation genetic testing to be a personal decision, discussion of these issues may be helpful.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

Chromosome Disorder Outreach Inc.
Phone: 561-395-4252
Email: info@chromodisorder.org
chromodisorder.org
Unique: Understanding Rare Chromosome and Gene Disorders
United Kingdom
Phone: +44 (0) 1883 723356
Email: info@rarechromo.org
rarechromo.org

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

17q12 Recurrent Deletion Syndrome: Genes and Databases

Gene	Chromosome Locus	Protein	Locus-Specific Databases	HGMD	ClinVar
HNF1B	17q12	Hepatocyte nuclear factor 1-beta	HNF1B database	HNF1B	HNF1B
LHX1	17q12	LIM/homeobox protein Lhx1		LHX1	LHX1

: Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for 17q12 Recurrent Deletion Syndrome (View All in OMIM)

137920	RENAL CYSTS AND DIABETES SYNDROME; RCAD
189907	HNF1 HOMEOBOX B; HNF1B
601999	LIM HOMEOBOX GENE 1; LHX1
614527	CHROMOSOME 17q12 DELETION SYNDROME

Molecular Pathogenesis

The 17q12 deletion is recurrent, meaning that it involves the same unique genomic sequence. The 17q12 region is considered a hot spot for copy number variants, as it has specific molecular features (known as segmental duplications) that predispose to these events [Mefford et al 2007, Moreno-De-Luca et al 2010].

Deletion mechanism. The 17q12 genomic region involved in the recurrent 17q12 deletion is flanked on each side by segmental duplications, which are highly repetitive segments of genomic material. Since these segmental duplications have a high degree of homology to one another, they can misalign during meiosis and give rise to deletions and duplications of the intervening genomic interval. This process, called nonallelic homologous recombination, accounts for the absence of the same unique genomic region in individuals with 17q12 recurrent deletion syndrome [Sharp et al 2006, Moreno-De-Luca et al 2010].

Genes of interest in this region. Genes within the 17q12 recurrent deletion region include AATF, ACACA, C17orf78, DDX52, DHRS11, DUSP14, GGNBP2, HNF1B, LHX1, MRM1, MYO19, PIGW, SYNRG, TADA2A, and ZNHIT3.

Three genes are of particular interest with respect to phenotypes associated with 17q12 recurrent deletion syndrome:

HNF1B. HNF1B haploinsufficiency has been established as the cause of the kidney, urogenital, and endocrine abnormalities that occur as part of 17q12 recurrent deletion syndrome. Heterozygous pathogenic sequence variants in HNF1B cause renal cysts and diabetes (RCAD) syndrome, which is characterized by the combination of congenital anomalies of the kidney and urinary tract (CAKUT) and maturity-onset diabetes of the young type 5 (MODY5) [Bingham et al 2001]. While other genes in the 17q12 recurrent deletion region likely account for most of the neurodevelopmental features associated with the syndrome, isolated sequence variants within HNF1B have also been associated with an increased risk for learning problems, albeit at a lesser frequency [Clissold et al 2016, Dubois-Laforgue et al 2017a, Laliève et al 2020]. Thus, more research is needed to define the role of HNF1B in the human brain.
LHX1. Heterozygous LHX1 likely pathogenic variants have been identified in females with müllerian aplasia / Mayer-Rokitansky-Küster-Hauser syndrome, though inheritance information was not available [Ledig et al 2011, Ledig et al 2012, Sandbacka et al 2013]. Because of its role in neural development, LHX1 may also contribute to the neurodevelopmental manifestations observed in 17q12 recurrent deletion syndrome [Moreno-De-Luca et al 2010, Nagamani et al 2010].
ACACA encodes acetyl-CoA carboxylase 1, involved in lipogenesis in adipose tissue. There has been speculation that haploinsufficiency of ACACA may contribute to the leaner phenotype and decreased risk of diabetic glomerular disease in individuals with 17q12 recurrent deletion syndrome compared to those with HNF1B sequence variants [Dubois-Laforgue et al 2017b].

Chapter Notes

Author Notes

Geisinger Autism & Developmental Medicine Institute
120 Hamm Drive, Suite 2
Lewisburg, PA 17837
Phone: +1-570-522-9430
Fax: +1-570-522-9431
Website: www.geisingeradmi.org

PRecISion Medicine in Autism (PRISMA) Group
University of Alberta
Phone: +1-780-492-4467

Email: ac.atreblau@amsirp
Website: www.precisionmedicineinautism.org

Dr Moreno De Luca (ac.atreblau@amsirp) is actively involved in clinical research regarding individuals with 17q12 recurrent deletion syndrome. He would be happy to communicate with persons who have any questions regarding diagnosis of 17q12 recurrent deletion syndrome or other considerations.

Acknowledgments

This work was funded in part by the National Institute for Mental Health of the National Institutes of Health under awards RO1MH074090 (to DHL and CLM), RO1MH107431 (to CLM), K23MH120376 (to DMD), and grants from the Simons Foundation (SFARI# 215355 to CLM and SFARI# 240413 to DHL). The authors would also like to thank all of the individuals and families with 17q12 deletions for their participation in these research studies.

Author History

Brenda Finucane, MS, LGC; Geisinger Health System (2016-2020)
David H Ledbetter, PhD, FACMG (2016-present)
Rebecca V Levy, BM BCh, MSc (2020-present)
Christa L Martin, PhD, FACMG (2016-present)
Marissa W Mitchel, MS, CCC-SLP (2016-present)
Daniel Moreno-De-Luca, MD, MSc (2016-present)
Scott M Myers, MD (2016-present)
Stefanie Turner, MS, CGC (2020-present)

Revision History

6 February 2025 (sw) Comprehensive update posted live
15 October 2020 (sw) Comprehensive update posted live
8 December 2016 (bp) Review posted live
10 August 2015 (mm) Original submission

References

Literature Cited

American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33:S62-9. [PMC free article: PMC2797383] [PubMed: 20042775]
Armstrong ME, Thomas CP. Diagnosis of monogenic chronic kidney diseases. Curr Opin Nephrol Hypertens. 2019;28:183-94. [PubMed: 30601180]
Bellanné-Chantelot C, Clauin S, Chauveau D, Collin P, Daumont M, Douillard C, Dubois-Laforgue D, Dusselier L, Gautier JF, Jadoul M, Laloi-Michelin M, Jacquesson L, Larger E, Louis J, Nicolino M, Subra JF, Wilhem JM, Young J, Velho G, Timsit J. Large genomic rearrangements in the hepatocyte nuclear factor-1beta (TCF2) gene are the most frequent cause of maturity-onset diabetes of the young type 5. Diabetes. 2005;54:3126-32. [PubMed: 16249435]
Berberich AJ, Wang J, Cao H, McIntyre AD, Spaic T, Miller DB, Stock S, Huot C, Stein R, Knoll J, Yang P, Robinson JF, Hegele RA. Simplifying detection of copy number variations in maturity onset diabetes of the young. Can J Diabetes. 2021;45:71-7. [PubMed: 33011132]
Bernardini L, Gimelli S, Gervasini C, Carella M, Baban A, Frontino G, Barbano G, Divizia MT, Fedele L, Novelli A, Béna F, Lalatta F, Miozzo M, Dallapiccola B. Recurrent microdeletion at 17q12 as a cause of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: two case reports. Orphanet J Rare Dis. 2009;4:25. [PMC free article: PMC2777856] [PubMed: 19889212]
Besse W, Dong K, Choi J, Punia S, Fedeles SV, Choi M, Gallagher AR, Huang EB, Gulati A, Knight J, Mane S, Tahvanainen E, Tahvanainen P, Sanna-Cherchi S, Lifton RP, Watnick T, Pei YP, Torres VE, Somlo S. Isolated polycystic liver disease genes define effectors of polycystin-1 function. J Clin Invest. 2017;127:1772-85. [PMC free article: PMC5409105] [PubMed: 28375157]
Bilezikian JP, Khan AA, Silverberg SJ, Fuleihan GE, Marcocci C, Minisola S, Perrier N, Sitges-Serra A, Thakker RV, Guyatt G, Mannstadt M. Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the fifth international workshop. J Bone Miner Res. 2022;37:2293-314. [PubMed: 36245251]
Bingham C, Ellard S, Nicholls AJ, Pennock CA, Allen J, James AJ, Satchell SC, Salzmann MB, Hattersley AT. The generalized aminoaciduria seen in patients with hepatocyte nuclear factor-1alpha mutations is a feature of all patients with diabetes and is associated with glucosuria. Diabetes. 2001;50:2047-52. [PubMed: 11522670]
Bleyer AJ, Wolf MT, Kidd KO, Zivna M, Kmoch S. Autosomal dominant tubulointerstitial kidney disease: more than just HNF1β. Pediatr Nephrol. 2022;37:933-46. [PMC free article: PMC8722360] [PubMed: 34021396]
Bockenhauer D, Jaureguiberry G. HNF1B-associated clinical phenotypes: the kidney and beyond. Pediatr Nephrol. 2016;31:707-14. [PubMed: 26160100]
Brännström M, Johannesson L, Dahm-Kähler P, Enskog A, Mölne J, Kvarnström N, Diaz-Garcia C, Hanafy A, Lundmark C, Marcickiewicz J, Gäbel M. First clinical uterus transplantation trial: a six-month report. Fertil Steril. 2014;101:1228-36. [PubMed: 24582522]
Buffin-Meyer B, Richard J, Guigonis V, Weber S, König J, Heidet L, Moussaoui N, Vu JP, Faguer S, Casemayou A, Prakash R. Renal and extrarenal phenotypes in patients with HNF1B variants and chromosome 17q12 microdeletions. Kidney Int Rep. 2024;9:2514-26. [PMC free article: PMC11328578] [PubMed: 39156164]
Bustamante C, Sanchez J, Seeherunvong T, Ukarapong S. Early onset of MODY5 due to haploinsufficiency of HNF1B. AACE Clin Case Rep. 2020;6:e243-e246. [PMC free article: PMC7511099] [PubMed: 32984530]
Carroll RW, Murphy R. Monogenic diabetes: a diagnostic algorithm for clinicians. Genes (Basel). 2013;4:522-35. [PMC free article: PMC3927568] [PubMed: 24705260]
Chen CP, Wu FT, Pan YT, Wu PS, Wang W. Prenatal diagnosis and perinatal findings of 17q12 microdeletion encompassing HNF1B in a fetus with bilateral hyperechogenic kidneys on fetal ultrasound and mild renal abnormality after birth, and a review of the literature of prenatal diagnosis of 17q12 microdeletion. Taiwan J Obstet Gynecol. 2024;63:77-80. [PubMed: 38216274]
Cheng Y, Zhong DP, Ren L, Yang H, Tian CF. Unusual manifestations of young woman with MODY5 based on 17q12 recurrent deletion syndrome. BMC Endocrine Disorders. 2022;22:77. [PMC free article: PMC8962578] [PubMed: 35346144]
Cheroki C, Krepischi-Santos AC, Szuhai K, Brenner V, Kim CA, Otto PA, Rosenberg C. Genomic imbalances associated with mullerian aplasia. J Med Genet. 2008;45:228-32. [PubMed: 18039948]
Cleper R, Reches A, Shapira D, Simchoni S, Reisman L, Ben-Sira L, Yaron Y, Wolman I, Malinger G, Brabbing-Goldstein D, Ben-Shachar S. Improving renal phenotype and evolving extra-renal features of 17q12 deletion encompassing the HNF1B gene. Translational Pediatrics. 2021;10:3130. [PMC free article: PMC8753471] [PubMed: 35070826]
Clissold RL, Ashfield B, Burrage J, Hannon E, Bingham C, Mill J, Hattersley A, Dempster EL. Genome-wide methylomic analysis in individuals with HNF1B intragenic mutation and 17q12 microdeletion. Clin Epigenetics. 2018;10:97. [PMC free article: PMC6052548] [PubMed: 30021660]
Clissold RL, Hamilton AJ, Hattersley AT, Ellard S, Bingham C. HNF1B-associated renal and extra-renal disease-an expanding clinical spectrum. Nat Rev Nephrol. 2015;11:102-12. [PubMed: 25536396]
Clissold RL, Shaw-Smith C, Turnpenny P, Bunce B, Bockenhauer D, Kerecuk L, Waller S, Bowman P, Ford T, Ellard S, Hattersley AT, Bingham C. Chromosome 17q12 microdeletions but not intragenic HNF1B mutations link developmental kidney disease and psychiatric disorder. Kidney Int. 2016;90:203-11. [PMC free article: PMC4915913] [PubMed: 27234567]
Committee on Adolescent Health Care. ACOG Committee Opinion No. 728: Müllerian agenesis: diagnosis, management, and treatment. Obstet Gynecol. 2018;131:e35-e42. [PubMed: 29266078]
Cornec-Le Gall E, Alam A, Perrone RD. Autosomal dominant polycystic kidney disease. Lancet. 2019;393:919-35. [PubMed: 30819518]
Crawford K, Bracher-Smith M, Owen D, Kendall KM, Rees E, Pardiñas AF, Einon M, Escott-Price V, Walters JT, O’Donovan MC, Owen MJ. Medical consequences of pathogenic CNVs in adults: analysis of the UK Biobank. J Med Genet. 2019;56:131-8. [PubMed: 30343275]
Dixit A, Patel C, Harrison R, Jarvis J, Hulton S, Smith N, Yates K, Silcock L, McMullan DJ, Suri M. 17q12 microdeletion syndrome: three patients illustrating the phenotypic spectrum. Am J Med Genet A. 2012;158A:2317-21. [PubMed: 22887843]
Dotto RP, Santana LS, Lindsey SC, Caetano LA, Franco LF, Moisés RC, Sa JR, Nishiura JL, Teles MG, Heilberg IP, Dias-da-Silva MR. Searching for mutations in the HNF1B gene in a Brazilian cohort with renal cysts and hyperglycemia. Arch Endocrinol Metab. 2019;63:250-7. [PMC free article: PMC10522195] [PubMed: 31066763]
Du T, Zeng N, Wen X, Zhu P, Li W. A rare combination of MODY5 and duodenal atresia in a patient: a case report. BMC Med Genet 2020;21:24. [PMC free article: PMC7006404] [PubMed: 32028929]
Dubois-Laforgue D, Bellanné-Chantelot C, Charles P, Jacquette A, Larger E, Ciangura C, Saint-Martin C, Rastel C, Keren B, Timsit J, Ajzenberg C. Intellectual disability in patients with MODY due to hepatocyte nuclear factor 1B (HNF1B) molecular defects. Diabetes Metab. 2017a;43:89-92. [PubMed: 27838256]
Dubois-Laforgue D, Cornu E, Saint-Martin C, Coste J, Bellanné-Chantelot C, Timsit J. Diabetes, associated clinical spectrum, long-term prognosis, and genotype/phenotype correlations in 201 adult patients with hepatocyte nuclear factor 1B (HNF1B) molecular defects. Diabetes Care. 2017b;40:1436-43. [PubMed: 28420700]
Eckardt KU, Alper SL, Antignac C, Bleyer AJ, Chauveau D, Dahan K, Deltas C, Hosking A, Kmoch S, Rampoldi L, Wiesener M, Wolf MT, Devuyst O. Autosomal dominant tubulointerstitial kidney disease: diagnosis, classification, and management--A KDIGO consensus report. Kidney Int. 2015;88:676-83. [PubMed: 25738250]
Edghill EL, Oram RA, Owens M, Stals KL, Harries LW, Hattersley AT, Ellard S, Bingham C. Hepatocyte nuclear factor-1B- a common cause of renal disease. Nephrol Dial Transplant. 2008;23:627-35. [PubMed: 17971380]
Faguer S, Bouissou F, Dumazer P, Guitard J, Bellane-Chentalot C, Chauveau D. Massively enlarged polycystic kidneys in monozygotic twins with TCF2/HNF-1B (hepatocyte nuclear factor-1B) heterozygous whole-gene deletion. Am J Kidney Dis. 2007;50:1023-7. [PubMed: 18037103]
Faguer S, Decramer S, Chassaing N, Bellanne-Chantelot C, Calvas P, Beaufils S, Bessenay L, Lengele JP, Dahan K, Ronco P, Devuyst O, Chauveau D. Diagnosis, management, and prognosis of HNF1B nephropathy in adulthood. Kidney Int. 2011;80:768-76. [PubMed: 21775974]
Fajans SS, Bell GI. MODY: history, genetics, pathophysiology, and clinical decision making. Diabetes Care. 2011;34:1878-84. [PMC free article: PMC3142024] [PubMed: 21788644]
Ferrè S, Bongers EM, Sonneveld R, Cornelissen EA, van der Vlag J, van Boekel GA, Wetzels JF, Hoenderop JG, Bindels RJ, Nijenhuis T. Early development of hyperparathyroidism due to loss of PTH transcriptional repression in patients with HNF1β mutations? J Clin Endocrinol Metab. 2013;98:4089-96. [PubMed: 23979948]
George AM, Love DR, Hayes I, Tsang B. Recurrent transmission of a 17q12 microdeletion and a variable clinical spectrum. Mol Syndromol. 2012;2:72-5. [PMC free article: PMC3326281] [PubMed: 22511894]
Goumy C, Laffargue F, Eymard-Pierre E, Kemeny S, Gaye-Bellile M, Gouas L, Gallot D, Francannet C, Tchirkov A, Pebrel-Richard C, Vago P. Congenital diaphragmatic hernia may be associated with 17q12 microdeletion syndrome. Am J Med Genet A. 2015;167A:250-3. [PubMed: 25425496]
Grozeva D, Conrad DF, Barnes CP, Hurles M, Owen MJ, O'Donovan MC, Craddock N, Kirov G. Independent estimation of the frequency of rare CNVs in the UK population confirms their role in schizophrenia. Schizophr Res. Schizophr Res. 2012;135:1-7. [PMC free article: PMC3315675] [PubMed: 22130109]
Hagan JF, Shaw JS, Duncan PM, eds. Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents. 4 ed. Elk Grove Village, IL: American Academy of Pediatrics; 2017.
Hasegawa Y, Takahashi Y, Nagasawa K, Kinno H, Oda T, Hangai M, Odashima Y, Suzuki Y, Shimizu J, Ando T, Egawa I. Japanese 17q12 deletion syndrome with complex clinical manifestations. Intern Med. 2024;63:687-92. [PMC free article: PMC10982014] [PubMed: 38432894]
Hendrix NW, Clemens M, Canavan TP, Surti U, Rajkovic A. Prenatally diagnosed 17q12 microdeletion syndrome with a novel association with congenital diaphragmatic hernia. Fetal Diagn Ther. 2012;31:129-33. [PubMed: 22178801]
Herlin MK. Genetics of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: advancements and implications. Front Endocrinol (Lausanne). 2024;15:1368990. [PMC free article: PMC11063329] [PubMed: 38699388]
Hinkes B, Hilgers KF, Bolz HJ, Goppelt-Struebe M, Amann K, Nagl S, Bergmann C, Rascher W, Eckardt K, Jacobi J. A complex microdeletion 17q12 phenotype in a patient with recurrent de novo membranous nephropathy. BMC Nephrol. 2012;13:27. [PMC free article: PMC3412739] [PubMed: 22583611]
Huang R, Fu F, Guo F, Zhou H, Yu Q, Yan S, Liu L, Lu J, Ma C, Wang Y, Chen H, Wang D, Zhang Y, Jing X, Li F, Han J, Li D, Li R, Liao C. Prenatal diagnosis of polycystic renal diseases: diagnostic yield, novel disease-causing variants, and genotype-phenotype correlations. Am J Obstet Gynecol MFM. 2024;6:101228. [PubMed: 37984685]
Hyman SL, Levy SE, Myers SM, et al. Clinical report: identification, evaluation, and management of children with autism spectrum disorder. Pediatrics. 2020;145:e20193447. [PubMed: 31843864]
Jing X-Y, Huang L-Y, Zhen L, Han J, Li D-Z. Prenatal diagnosis of 17q12 deletion syndrome: a retrospective case series. J Obstet Gynaecol. 2019;39:323-7. [PubMed: 30634886]
Jones GE, Mousa HA, Rowley H, Houtman P, Vasudevan PC. Should we offer prenatal testing for 17q12 microdeletion syndrome to all cases with prenatally diagnosed echogenic kidneys? Prenatal findings in two families with 17q12 microdeletion syndrome and review of the literature. Prenat Diagn. 2015;35:1336-41. [PubMed: 26429400]
Kasperavičiūtė D, Catarino CB, Chinthapalli K, Clayton LMS, Thom M, Martinian L, Cohen H, Adalat S, Bockenhauer D, Pope SA, Lench N, Koltzenburg M, Duncan JS, Hammond P, Hennekam RCM, Land JM, Sisodiya SM. Uncovering genomic causes of co-morbidity in epilepsy: gene-driven phenotypic characterization of rare microdeletions. PLoS One. 2011;6:e23182. [PMC free article: PMC3157359] [PubMed: 21858020]
Kołbuc M, Leßmeier L, Salamon-Słowińska D, Małecka I, Pawlaczyk K, Walkowiak J, Wysocki J, Beck BB, Zaniew M. Hypomagnesemia is underestimated in children with HNF1B mutations. Pediatr Nephrol. 2020;35:1877-86. [PubMed: 32388583]
Kołbuc M, Kołek MF, Motyka R, Bieniaś B, Habbig S, Burgmaier K, Prikhodina L, Papizh S, Tasic V, Okorn C, Szczepańska M. Development of a tool for predicting HNF1B mutations in children and young adults with congenital anomalies of the kidneys and urinary tract. Pediatr Nephrol. 2024;39:1847-58. [PMC free article: PMC11026189] [PubMed: 38196016]
Kotalova R, Dusatkova P, Cinek O, Dusatkova L, Dedic T, Seeman T, Lebl J, Pruhova S. Hepatic phenotypes of HNF1B gene mutations: a case of neonatal cholestasis requiring portoenterostomy and literature review. World J Gastroenterol. 2015;21:2550-7. [PMC free article: PMC4342936] [PubMed: 25741167]
Kumar A, Hollar L, McGill JB, Thaker PH, Salam M. MODY5 and serous ovarian carcinoma in 17q12 recurrent deletion syndrome. AACE Clin Case Rep. 2023;9:112-5. [PMC free article: PMC10382612] [PubMed: 37520763]
Laffargue F, Bourthoumieu S, Llanas B, Baudouin V, Lahoche A, Morin D, Bessenay L, De Parscau L, Cloarec S, Delrue M, Taupiac E, Dizier E, Laroche C, Bahans C, Yardin C, Lacombe D, Guigonis V. Towards a new point of view on the phenotype of patients with a 17q12 microdeletion syndrome. Arch Dis Child. 2015;100:259-64. [PubMed: 25324567]
Laliève F, Decramer S, Heidet L, Baudouin V, Lahoche A, Llanas B, Cochat P, Tenenbaum J, Lavocat MP, Eckart P, Broux F, Roussey G, Cloarec S, Vrillon I, Dunand O, Bessenay L, Tsimaratos M, Nobili F, Pietrement C, De Parscau L, Bonneville V, Rodier N, Saint-Martin C, Chassaing N, Michel-Calemard L, Moriniere V, Bellanné-Chantelot C, Bahans C, Guigonis V. School level of children carrying a HNF1B variant or a deletion. Eur J Hum Genet. 2020;28:56–63. [PMC free article: PMC6906503] [PubMed: 31481685]
Lanktree MB, Iliuta IA, Haghighi A, Song X, Pei Y. Evolving role of genetic testing for the clinical management of autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2019;34:1453-60. [PubMed: 30165646]
Ledig S, Brucker S, Barresi G, Schomburg J, Rall K, Wieacker P. Frame shift mutation of LHX1 is associated with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. Hum Reprod. 2012;27:2872-5. [PubMed: 22740494]
Ledig S, Schippert C, Strick R, Beckmann MW, Oppelt PG, Wieacker P. Recurrent aberrations identified by array-CGH in patients with Mayer-Rokitansky-Kuster-Hauser syndrome. Fertil Steril. 2011;95:1589-94. [PubMed: 20797712]
Lee R, Choi JE, Mun E, Kim KH, Choi SA, Kim HS. A case of chromosome 17q12 deletion syndrome with type 2 Mayer–Rokitansky–Küster–Hauser syndrome and maturity-onset diabetes of the young type 5. Children. 2024;11:404. [PMC free article: PMC11049139] [PubMed: 38671621]
Li HJ, Groden C, Hoenig MP, Ray EC, Ferreira CR, Gahl W, Novacic D. Case report: extreme coronary calcifications and hypomagnesemia in a patient with a 17q12 deletion involving HNF1B. BMC Nephrol. 2019;20:353. [PMC free article: PMC6734489] [PubMed: 31500578]
Lim SH, Kim JH, Han KH, Ahn YH, Kang HG, Ha I-S, Cheong HI. Genotype and phenotype analyses in pediatric patients with HNF1B mutations. J Clin Med. 2020;9:2320. [PMC free article: PMC7408390] [PubMed: 32708349]
Loirat C, Bellane-Chantelot C, Husson I, Deschenes G, Guigonis, V, Chabane N. Autism in three patients with cystic or hyperechogenic kidneys and chromosome 17q12 deletion. Nephrol Dial Transplant. 2010;25:3430-3. [PubMed: 20587423]
Lord C, Charman T, Havdahl A, Carbone P, Anagnostou E, Boyd B, et al. The Lancet Commission on the future of care and clinical research in autism. Lancet. 2022;399:271-334. [PubMed: 34883054]
Madariaga L, García-Castaño A, Ariceta G, Martínez-Salazar R, Aguayo A, Castaño L, et al. Variable phenotype in HNF1B mutations: extrarenal manifestations distinguish affected individuals from the population with congenital anomalies of the kidney and urinary tract. Clin Kidney J. 2018;12:373-9. [PMC free article: PMC6543961] [PubMed: 31198537]
Madariaga L, Morinière V, Jeanpierre C, Bouvier R, Loget P, Martinovic J, Dechelotte P, Leporrier N, Thauvin-Robinet C, Jensen UB, Gaillard D, Mathieu M, Turlin B, Attie-Bitach T, Salomon R, Gübler MC, Antignac C, Heidet L. Severe prenatal renal anomalies associated with mutations in HNF1B or PAX2 genes. Clin J Am Soc Nephrol 2013;8:1179-87. [PMC free article: PMC3700697] [PubMed: 23539225]
Mefford HC, Clauin S, Sharp AJ, Moller RS, Ullmann R, Kapur R, Pinkel D, Cooper GM, Ventura M, Ropers HH, Tommerup N, Eichler EE, Bellanne-Chantelot C. Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy. Am J Hum Genet. 2007;81:1057-69. [PMC free article: PMC2265663] [PubMed: 17924346]
Milone R, Tancredi R, Cosenza A, Ferrari AR, Scalise R, Cioni G, Battini R. 17q12 recurrent deletions and duplications: description of a case series with neuropsychiatric phenotype. Genes. 2021;12:1660. [PMC free article: PMC8620923] [PubMed: 34828266]
Moreno-De-Luca D, Mulle JG, Kaminsky EB, SGENE Consortium, Simons Simplex Collection Genetics Consortium, Sanders SJ, GeneSTAR, Myers SM, Adam MP, Pakula AT, Eisenhauer NJ, Uhas K, Weik L, Guy L, Care ME, Morel CF, Boni C, Salbert BA, Chandrareddy A, Demmer LA, Chow EW, Surti U, Aradhya S, Pickering DL, Golden DM, Sanger WG, Aston E, Brothman AR, Gliem TJ, Thorland EC, Ackley T, Iyer R, Huang S, Barber JC, Crolla JA, Warren ST, Martin CL, Ledbetter DH. Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia. Am J Hum Genet. 2010;87:618-30. [PMC free article: PMC2978962] [PubMed: 21055719]
Motyka R, Kołbuc M, Wierzchołowski W, Beck BB, Towpik IE, Zaniew M. Four cases of maturity onset diabetes of the young (MODY) type 5 associated with mutations in the hepatocyte nuclear factor 1 beta (HNF1B) gene presenting in a 13-year-old boy and in adult men aged 33, 34, and 35 years in Poland. Am J Case Rep. 2021;22:e928994-1. [PMC free article: PMC7869582] [PubMed: 33526762]
Nagamani SCS, Erez A, Shen J, Li C, Roeder E, Cox S, Karaviti L, Pearson M, Kang SL, Sahoo T, Lalani SR, Stankiewicz P, Sutton VR, Cheung SW. Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12. Eur J Hum Genet. 2010;18:278-84. [PMC free article: PMC2987224] [PubMed: 19844256]
Naylor RN, Patel KA, Kettunen JL, Männistö JM, Støy J, Beltrand J, Polak M, Vilsbøll T, Greeley SA, Hattersley AT. Precision treatment of beta-cell monogenic diabetes: a systematic review. Commun Med (Lond). 2024;4:145. [PMC free article: PMC11258280] [PubMed: 39025920]
NIH. Office of Dietary Supplements. Magnesium: fact sheet for health professionals. 2018. Available online. Accessed on 8-24-22.
Nik-Zainal S, Strick R, Storer M, Huang N, Rad R, Willatt L, Fitzgerald T, Martin V, Sandford R, Carter NP, Janecke AR, Renner SP, Oppelt PG, Oppelt P, Schulze C, Brucker S, Hurles M, Beckmann MW, Strissel PL, Shaw-Smith C. High incidence of recurrent copy number variants in patients with isolated and syndromic Müllerian aplasia. J Med Genet. 2011;48:197-204. [PMC free article: PMC3322361] [PubMed: 21278390]
Nittel CM, Dobelke F, König J, Konrad M, Becker K, Kamp-Becker I, Weber S; NEOCYST consortium. Review of neurodevelopmental disorders in patients with HNF1B gene variations. Front Pediatr. 2023;11:1149875. [PMC free article: PMC10034397] [PubMed: 36969268]
Oh AJ, Javaheri M, Hosseini H, Prasad PS. Purtscher-like retinopathy in a 19-year-old with maturity-onset diabetes of the young: a case report. J Med Case Rep. 2023;17:255. [PMC free article: PMC10278244] [PubMed: 37331978]
Okorn C, Goertz A, Vester U, Beck BB, Bergmann C, Habbig S, König J, Konrad M, Müller D, Oh J, Ortiz-Brüchle N. HNF1B nephropathy has a slow-progressive phenotype in childhood—with the exception of very early onset cases: results of the German Multicenter HNF1B Childhood Registry. Pediatr Nephrol. 2019;34:1065-75. [PubMed: 30666461]
Oram RA, Edghill EL, Blackman J, Taylor MJO, Kay T, Flanagan SE, Ismail-Pratt I, Creighton SM, Ellard S, Hattersley AT, Bingham C. Mutations in the hepatocyte nuclear factor-1B (HNF1B) gene are common with combined uterine and renal malformations but are not found with isolated uterine malformations. Am J Obstet Gynecol. 2010;203:364.e1-5. [PubMed: 20633866]
Palumbo P, Antona V, Palumbo O, Piccione M, Nardello R, Fontana A, Carella M, Corsello G. Variable phenotype in 17q12 microdeletions: clinical and molecular characterization of a new case. Gene. 2014;538:373-8. [PubMed: 24487052]
Pinon M, Carboni M, Colavito D, Cisarò F, Peruzzi L, Pizzol A, Calosso G, David E, Calvo PL. Not only Alagille syndrome. Syndromic paucity of interlobular bile ducts secondary to HNF1β deficiency: a case report and literature review. Ital J Pediatr. 2019;45:27. [PMC free article: PMC6385394] [PubMed: 30791938]
Poitou C, Francois H, Bellanne-Chantelot C, Noel C, Jacquet A, Clauin S, Beaudreuil S, Damieri H, Hebibi H, Hammoudi Y, Benoit G, Charpentier B, Durrbach A. Maturity-onset diabetes of the young: clinical characteristics and outcome after kidney and pancreas transplantation in MODY3 and RCAD patients: a single center experience. Transpl Int. 2012;25:564-72. [PubMed: 22432796]
Porath B, Gainullin VG, Cornec-Le Gall E, Dillinger EK, Heyer CM, Hopp K, Edwards ME, Madsen CD, Mauritz SR, Banks CJ, Baheti S, Reddy B, Herrero JI, Bañales JM, Hogan MC, Tasic V, Watnick TJ, Chapman AB, Vigneau C, Lavainne F, Audrézet MP, Ferec C, Le Meur Y, Torres VE, Harris PC, et al. Mutations in GANAB, encoding the glucosidase IIα subunit, cause autosomal-dominant polycystic kidney and liver disease. Am J Hum Genet. 2016;98:1193-207. [PMC free article: PMC4908191] [PubMed: 27259053]
Quintero-Rivera F, Woo JS, Bomberg EM, Wallace WD, Peredo J, Dipple KM. Duodenal atresia in 17q12 microdeletion including HNF1B: a new associated malformation in this syndrome. Am J Med Genet A. 2014;164A:3076-82. [PubMed: 25256560]
Raaijmakers A, Corveleyn A, Devriendt K, van Tienoven TP, Allegaert K, Van Dyck M, van den Heuvel L, Kuypers D, Claes K, Mekahli D, Levtchenko E. Criteria for HNF1B analysis in patients with congenital abnormalities of kidney and urinary tract. Nephrol Dial Transplant 2015;30:835-42. [PubMed: 25500806]
Raile K, Klopocki E, Holder M, Wessel T, Galler A, Deiss D, Muller D, Riebel T, Horn D, Maringa M, Weber J, Ullmann R, Gruters A. Expanded clinical spectrum in hepatocyte nuclear factor 1B — maturity-onset diabetes of the young. J Clin Endocrinol Metab. 2009;94:2658-64. [PubMed: 19417042]
Rasmussen M, Vestergaard EM, Graakjaer J, Petkov Y, Bache I, Fagerberg C, Kibaek M, Svaneby D, Petersen OB, Brasch-Andersen C, Sunde L. 17q12 deletion and duplication syndrome in Denmark-a clinical cohort of 38 patients and review of the literature. Am J Med Genet A. 2016;170:2934-42. [PubMed: 27409573]
Roberts JL, Gandomi SK, Parra M, Lu I, Gau CL, Dasouki M, Butler MG. Clinical report of a 17q12 microdeletion with additionally unreported clinical features. Case Rep Genet. 2014;2014:264947. [PMC free article: PMC4060289] [PubMed: 24991439]
Roehlen N, Hilger H, Stock F, Gläser B, Guhl J, Schmitt-Graeff A, Seufert J, Laubner K. 17q12 deletion syndrome as a rare cause for diabetes mellitus type MODY5. J Clin Endocrinol Metab. 2018;103:3601-10. [PubMed: 30032214]
Sandbacka M, Laivuori H, Freitas E, Halttunen M, Jokimaa V, Morin-Papunen L, Rosenberg C, Aittomaki K. TBX6, LHX1 and copy number variations in the complex genetics of Mullerian aplasia. Orphanet J Rare Dis. 2013;8:125. [PMC free article: PMC3847609] [PubMed: 23954021]
Sanna-Cherchi S, Kiryluk K, Burgess KE, Bodria M, Sampson MG, Hadley D, Nees SN, Verbitsky M, Perry BJ, Sterken R, Lozanovski VJ, Matema-Kiryluk A, Barlassina C, Kini A, Corbania V, Carrea A, Somenzi D, Murtas C, Ristoska-Bojkovska N, Izzi C, Bianco B, Zaniew M, Flogelova H, Weng PL, Kacak N, Giberti S, Gigante M, Arapovic A, Drnasin K, Caridi G, Curioni S, Allegri F, Ammenti A, Ferretti S, Goj V, Bernardo L, Jobanputra V, Chung WK, Lifton RP, Sanders S, State M, Clark LN, Saraga M, Padmanabhan S, Dominiczak AF, Foroud T, Gesualdo L, Gucev Z, Allegri L, Latos-Bielenska A, Cusi D, Scolari F, Tasic V, Hakonarson H, Ghiggeri GM, Gharavi AG. Copy-number disorders are a common cause of congenital kidney malformations. Am J Hum Genet. 2012;91:987-97. [PMC free article: PMC3516596] [PubMed: 23159250]
Shah CV, Hammad N, Bhasin-Chhabra B, Rashidi A. SGLT2 inhibitors in management of severe hypomagnesemia in patients without diabetes: a report of 4 cases. Kidney Med. 2023;5:100697. [PMC free article: PMC10432792] [PubMed: 37602145]
Sharp AJ, Hansen S, Selzer RR, Cheng Z, Regan R, Hurst JA, Stewart H, Price SM, Blair E, Hennekam RC, Fitzpatrick CA, Segraves R, Richmond TA, Guiver C, Albertson DG, Pinkel D, Eis PS, Schwartz S, Knight SJ, Eichler EE. Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome. Nat Genet. 2006;38:1038-42. [PubMed: 16906162]
Siegel M, McGuire K, Veenstra-VanderWeele J, Stratigos K, King B, Bellonci C, Hayek M, Keable H, Rockhill C, Bukstein OG, Walter HJ. Practice parameter for the assessment and treatment of psychiatric disorders in children and adolescents with intellectual disability (intellectual developmental disorder). J Am Acad Child Adolesc Psychiatry. 2020;59:468-96. [PubMed: 33928910]
Smajlagić D, Lavrichenko K, Berland S, Helgeland Ø, Knudsen GP, Vaudel M, Haavik J, Knappskog PM, Njølstad PR, Houge G, Johansson S. Population prevalence and inheritance pattern of recurrent CNVs associated with neurodevelopmental disorders in 12,252 newborns and their parents. Eur J Hum Genet. 2021;29:205-15. [PMC free article: PMC7852900] [PubMed: 32778765]
Soares AR, Figueiredo CM, Quelhas D, Silva ES, Freitas J, Oliveira MJ, Faria S, Fortuna AM, Borges T. Hyperinsulinaemic hypoglycaemia and polycystic kidney disease - a rare case concerning PMM2 gene pleiotropy. Eur Endocrinol. 2020;16:66-8. [PMC free article: PMC7308104] [PubMed: 32595772]
Song CY, Yang J, Jiang S, Du GL. HNF1β, LHX1, and GGNBP2 deletion contributed to kidney and reproductive dysfunction in 17q12 deletion syndrome: evidence from a case report. Front Genet. 2024;15:1391804. [PMC free article: PMC11361975] [PubMed: 39221224]
Stefansson H, Meyer-Lindenberg A, Steinberg S, Magnusdottir B, Morgen K, Arnarsdottir S, Bjornsdottir G, Walters GB, Jonsdottir GA, Doyle OM, Tost H, Grimm O, Krisjansdottir S, Snorrason H, Davidsdottir SR, Gudmundsson LJ, Jonsson GF, Stefansdottir B, Helgadottir I, Haraldsson M, Jonsdottir B, Thygesen JH, Schwarz AJ, Didriksen M, Stensbol TB, Brammer M, Kapur S, Halldorsson JG, Hreidarsson S, Saemundsen E, Sigurdsson E, Stefansson K. CNVs conferring risk of autism or schizophrenia affect cognition in controls. Nature. 2014;505:361-6. [PubMed: 24352232]
Stevens PE, Ahmed SB, Carrero JJ, Foster B, Francis A, Hall RK, Herrington WG, Hill G, Inker LA, Kazancıoğlu R, Lamb E. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024;105:S117-314. [PubMed: 38490803]
Stiles CE, Thuraisingham R, Bockenhauer D, Platts L, Kumar AV, Korbonits M. De novo HNF1 homeobox B mutation as a cause for chronic, treatment-resistant hypomagnesaemia. Endocrinol Diabetes Metab Case Rep. 2018;2018:17-0120. [PMC free article: PMC5863246] [PubMed: 29576871]
Sztromwasser P, Michalak A, Małachowska B, Młudzik P, Antosik K, Hogendorf A, Zmysłowska A, Borowiec M, Młynarski W, Fendler W. A cross-sectional study of patients referred for HNF1B-MODY genetic testing due to cystic kidneys and diabetes. Pediatr Diabetes. 2020;21:422-30. [PMC free article: PMC7217165] [PubMed: 31825128]
Thewjitcharoen Y, Nakasatien S, Tsoi TF, Lim CK, Himathongkam T, Chan JC. Hypertriglyceridemia as a main feature associated with 17q12 deletion syndrome-related hepatocyte nuclear factor 1β-maturity-onset diabetes of the young. Endocrinol Diabetes Metab Case Rep. 2022. Epub ahead of print. [PMC free article: PMC9513634] [PubMed: 36106561]
Vaez M, Montalbano S, Calle Sánchez X, Georgii Hellberg KL, Dehkordi SR, Krebs MD, Meijsen J, Shorter J, Bybjerg-Grauholm J, Mortensen PB, Børglum AD, Hougaard DM, Nordentoft M, Geschwind DH, Buil A, Schork AJ, Helenius D, Raznahan A, Thompson WK, Werge T, Ingason A; iPSYCH Investigators. Population-based risk of psychiatric disorders associated with recurrent copy number variants. JAMA Psychiatry. 2024;81:957-66. [PMC free article: PMC11209205] [PubMed: 38922630]
van der Made CI, Hoorn EJ, de la Faille R, Karaaslan H, Knoers NV, Hoenderop JG, Vargas Poussou R, de Baaij JH. Hypomagnesemia as first clinical manifestation of ADTKD-HNF1B: a case series and literature review. Am J Nephrol. 2015;42:85-90. [PubMed: 26340261]
Vasileiou G, Hoyer J, Thiel CT, Schaefer J, Zapke M, Krumbiegel M, Kraus C, Zweier M, Uebe S, Ekici AB, Schneider M. Prenatal diagnosis of HNF1B-associated renal cysts: need to differentiate intragenic variants from 17q12 microdeletion syndrome? Prenat Diagn. 2019;39:1136-47. [PubMed: 31498910]
Verbitsky M, Sanna-Cherchi S, Fasel DA, Levy B, Kiryluk K, Wuttke M, Abraham AG, Kaskel F, Kottgen A, Warady BA, Furth SL, Wong CS, Gharavi AG. Genomic imbalances in pediatric patients with chronic kidney disease. J Clin Invest. 2015;125:2171-8. [PMC free article: PMC4463214] [PubMed: 25893603]
Verhave JC, Bech AP, Wetzels JF, Nijenhuis T. Hepatocyte nuclear factor 1β-associated kidney disease: more than renal cysts and diabetes. J Am Soc Nephrol 2016;27:345-53. [PMC free article: PMC4731131] [PubMed: 26319241]
Verscaj CP, Velez-Bartolomei F, Bodle E, Chan K, Lyons MJ, Thorson W, Tan WH, Rodig N, Graham Jr JM, Peron A, Quintero-Rivera F. Characterization of the prenatal renal phenotype associated with 17q12, HNF1B, microdeletions. Prenat Diagn. 2024;44:237-46. [PubMed: 37632214]
Volkmar F, Siegel M, Woodbury-Smith M, King B, McCracken J, State M, et al. Practice parameter for the assessment and treatment of children and adolescents with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2014;53:237-57. [PubMed: 24472258]
Wan S, Zheng Y, Dang Y, Song T, Chen B, Zhang J. Prenatal diagnosis of 17q12 microdeletion and microduplication syndrome in fetuses with congenital renal abnormalities. Mol Cytogenet 2019;12:19. [PMC free article: PMC6525371] [PubMed: 31131025]
Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, Savage M, Saltzman D, Grobman WA, Klugman S, Scholl T, Simpson JL, McCall K, Aggarwal VS, Bunke B, Nahum O, Patel A, Lamb AN, Thom EA, Beaudet AL, Ledbetter DH, Shaffer LG, Jackson L. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 2012:367:2175-84. [PMC free article: PMC3549418] [PubMed: 23215555]
Whitcomb DC, Buchner AM, Forsmark CE. AGA clinical practice update on the epidemiology, evaluation, and management of exocrine pancreatic insufficiency: expert review. Gastroenterology. 2023;165:1292-301. [PubMed: 37737818]
Xin S, Zhang X. Case report: diabetes mellitus type MODY5 as a feature of 17q12 deletion syndrome with diabetic gastroparesis. Front Endocrinol (Lausanne). 2023;14:1205431. [PMC free article: PMC10682700] [PubMed: 38033996]
Zhang F, Gu Q, Song J, Zhao Y, Wang Z, Men S, Wang L. Prenatal diagnosis and family analysis of 17q12 microdeletion syndrome with fetal renal abnormalities. Front Genet. 2024;15:1401315. [PMC free article: PMC11217314] [PubMed: 38957807]
Zuber J, Bellanne-Chantelot C, Carette C, Canaud G, Gobrecht S, Gaha K, Mallet V, Martinez F, Thervet E, Timsit J, Legendre C, Dubois-Laforgue D. HNF1B-related diabetes triggered by renal transplantation. Nat Rev Nephrol. 2009;5:480-4. [PubMed: 19639018]

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Mitchel MW, Moreno-De-Luca D, Myers SM, et al. 17q12 Recurrent Deletion Syndrome. 2016 Dec 8 [Updated 2025 Feb 6]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025.
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17q12 Recurrent Deletion Syndrome

Summary

Clinical characteristics.

Diagnosis/testing.

Management.

Genetic counseling.

Diagnosis

Suggestive Findings

Establishing the Diagnosis

Table 1.

Clinical Characteristics

Clinical Description

Table 2.

Most Common Features (>50%)

Common Features (25%-50%)

Less Common Features (<25%)

Penetrance

Prevalence

Genetically Related Disorders

Differential Diagnosis

Table 3.

Management

Evaluations Following Initial Diagnosis

Table 4.

Treatment of Manifestations

Table 5.

Surveillance

Table 6.

Agents/Circumstances to Avoid

Evaluation of Relatives at Risk

Therapies Under Investigation

Genetic Counseling

Mode of Inheritance

Risk to Family Members

Related Genetic Counseling Issues

Prenatal Testing and Preimplantation Genetic Testing

Resources

Molecular Genetics

Table A.

Table B.

Molecular Pathogenesis

Chapter Notes

Author Notes

Acknowledgments

Author History

Revision History

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