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17q12 Recurrent Duplication

, MD, PhD.

Author Information

Initial Posting: ; Last Revision: January 13, 2022.

Estimated reading time: 18 minutes

Summary

Clinical characteristics.

The 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%. Additional common findings include microcephaly, ocular abnormalities, and endocrine abnormalities. Short stature and renal and cardiac abnormalities are also reported in some individuals. Penetrance is incomplete and clinical findings are variable.

Diagnosis/testing.

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

Management.

Treatment of manifestations: Those with developmental delays, cognitive disability, and/or behavioral problems should be evaluated by a neurodevelopmental pediatrician or clinical psychologist/psychiatrist. Seizures should be managed by a neurologist using standard practice. Feeding therapy as needed. Individuals with vision, endocrine, cardiac, and/or renal abnormalities should be managed by the appropriate specialist.

Surveillance: Regular assessment of psychomotor development is recommended for all children with the 17q12 recurrent duplication as well as psychological evaluation in both affected children and adults. Monitor for new-onset seizures, growth and nutritional assessment, and assessment of family needs at each visit.

Evaluation of relatives at risk: Presymptomatic diagnosis and treatment is warranted in at-risk relatives to identify as early as possible those who would benefit from close assessment/monitoring of developmental milestones in childhood or psychological assessment/intervention through adulthood.

Genetic counseling.

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. Prenatal testing for an at-risk pregnancy requires prior identification of the duplication in an affected family member. Interpretation of results from prenatal testing is challenging given the inherent difficulty in accurately predicting the phenotype.

Diagnosis

Suggestive Findings

The 17q12 recurrent duplication should be suspected in individuals with the following:

  • Intellectual disability
  • Developmental delays
  • Seizures
  • Ocular anomalies and/or vision problems
  • Cardiac malformations
  • Renal malformations
  • Gastrointestinal abnormalities (e.g., duodenal obstruction)

Establishing the Diagnosis

The diagnosis of the 17q12 recurrent duplication is established in a proband by detection of the 1.4-Mb heterozygous duplication at chromosome 17q12 (see Table 1 and Molecular Genetics).

For this GeneReview, the 17q12 recurrent duplication is defined as the presence of a recurrent 1.4-Mb heterozygous duplication at the approximate position of chr17:36,459,259-37,832,869 Mb in the reference genome (NCBI Build GRCh38/hg38).

Note: The phenotype of significantly larger or smaller duplications or deletions within this region may be clinically distinct from the 17q12 recurrent duplication (see Genetically Related Disorders).

For information on the 15 known genes within the 17q12 region see Molecular Genetics.

Genomic testing methods that determine the copy number of sequences can include chromosomal microarray (CMA) or targeted deletion analysis.

Note: The 17q12 recurrent duplication is submicroscopic and cannot be identified by routine analysis of G-banded chromosomes or other conventional cytogenetic banding techniques.

  • CMA using oligonucleotide or SNP arrays can detect the recurrent duplication in a proband. The ability to size the duplication depends on the type of microarray used and the density of probes in the 17q12 region.
    Note: (1) Most individuals with the 17q12 recurrent duplication are identified by CMA performed in the context of developmental delay, intellectual disability, and/or autism spectrum disorders. (2) Prior to 2008, many CMA platforms did not include coverage for this region and thus may not have detected this duplication.
  • Targeted duplication analysis. 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 duplication.
    Note: (1) Targeted duplication testing is not appropriate for an individual in whom the 17q12 recurrent duplication was not detected by CMA designed to target this region. (2) It is not possible to size the duplication routinely by use of targeted methods.

Table 1.

Genomic Testing Used in the 17q12 Recurrent Duplication

Duplication 1MethodSensitivity
ProbandAt-risk family members
1.4-Mb heterozygous duplication at 17q12
ISCN: seq[GRCh38] del(17)(q12) chr17:36,459,259-37,832,869 del 2
ClinGen ID: ISCA-37432
CMA 3100%100%
Targeted duplication analysis 4NA 5Up to 100% 6
1.

See Molecular Genetics for details of the duplication and genes of interest included in the region.

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). The region is identified in dbVar (www​.ncbi.nlm.nih.gov/dbvar) as nsv491563. Genomic coordinates represent the minimum duplication size associated with the 17q12 recurrent duplication as designated by ClinGen. Duplication coordinates may vary slightly based on array design used by the testing laboratory. Note that the size of the duplication as calculated from these genomic positions may differ from the expected duplication size due to the presence of segmental duplications near breakpoints. The phenotype of significantly larger or smaller duplications within this region may be clinically distinct from that of the recurrent 17q12 duplication (see Genetically Related Disorders).

3.

Chromosomal microarray analysis (CMA) using oligonucleotide or SNP arrays. CMA designs in current clinical use target the 17q12 region. Note: The 17q12 recurrent duplication may not have been detectable by older oligonucleotide or BAC platforms.

4.

Targeted duplication analysis methods can include FISH, quantitative PCR (qPCR), and multiplex ligation-dependent probe amplification (MLPA) as well as other targeted quantitative methods.

5.

Targeted duplication analysis is not appropriate for an individual in whom the 17q12 recurrent duplication was not detected by CMA designed to target this region.

6.

Targeted duplication analysis may be used to test at-risk relatives of a proband known to have the 17q12 recurrent duplication.

Clinical Characteristics

Clinical Description

To date, published reports include 86 individuals with the 17q12 recurrent duplication, along with some phenotypic data [Sharp et al 2006, Mefford et al 2007, Mencarelli et al 2008, Nagamani et al 2010, Faguer et al 2011, Brandt et al 2012, Bierhals et al 2013, Girirajan et al 2013, Hardies et al 2013, Smigiel et al 2014, Casey et al 2015, Mitchell et al 2015, Rasmussen et al 2016, Kamath et al 2018, Kotalova et al 2018, Zhang et al 2021, Zhou et al 2021]. Individuals found to have this rare duplication were typically referred for testing because of intellectual disability and/or developmental delays, and occasionally because of multiple congenital anomalies. The 17q12 recurrent duplication likely also has reduced penetrance and variable expressivity since it is inherited in most instances from a parent with findings reported to be minimally abnormal or normal.

Table 2.

Frequency of Phenotypic Features in 86 Reported Individuals with 17q12 Recurrent Duplication

Phenotypic Feature% of Persons with Feature
Intellectual disability71%
Speech delay65%
Gross motor delay49%
OFC <5th centile41%
Behavioral abnormalities62%
Seizures/Epilepsy36%
Hypotonia73%
Other neurologic abnormalities85%
Height <5th centile22%
Ophthalmologic abnormalities28%
Weight <5th centile21%
Endocrine abnormalities26%
Weight >95th centile13%
Cardiac abnormalities14%
Renal abnormalities20%
Height >95th centile6%

Developmental delay (DD) and intellectual disability (ID). Intellectual abilities range from normal to severe ID. The majority of affected individuals (71%) are reported to have delays or ID. However, the true incidence may be lower given variable expressivity and the ascertainment bias that is present due to the fact that most individuals who are found to have the 17q12 duplication are referred because of DD or ID. Speech delay is common (65%). Most affected individuals (49%-73%) have some degree of hypotonia and gross motor delay.

Behavioral and psychiatric conditions reported in a subset of affected individuals are autism spectrum disorder, schizophrenia, and behavioral abnormalities (including aggression, self-injurious behaviors, and compulsive disorders).

Seizures are reported in 36% of affected individuals.

Brain MRI occasionally reveals abnormalities including focal cortical dysplasia, agenesis of the corpus callosum, periventricular leukomalacia, and schizencephaly.

Microcephaly is reported in approximately 40% of individuals.

Eye and/or vision abnormalities including strabismus, astigmatism, amblyopia, cataract, coloboma, and microphthalmia occur in up to 28% of individuals.

Growth is variable. Both short (22%) and tall (6%) stature have been reported. Prenatal detection of short femur and humerus was reported in one fetus.

Endocrine abnormalities, reported in 26% of individuals, are variable and include diabetes insipidus, type 2 diabetes, growth hormone deficiency, hypoglycemia, hyponatremia and hyperkalemia, and pseudohypoaldosteronism.

Cardiac. The most common reported congenital heart defect is a small ventricular septal defect.

Renal abnormalities, present in approximately 20% of individuals, include horseshoe kidney, renal cysts, and hypoplastic kidneys.

Facial features. No specific dysmorphic features have been consistently observed. If present, dysmorphic features are nonspecific.

Other

  • Tracheoesophageal fistula has been reported in three individuals.
  • Duodenal atresia has been reported in three individuals.

Penetrance

The penetrance of the 17q12 recurrent duplication has not been established. Although an estimated penetrance of approximately 21% has been proposed [Rosenfeld et al 2013], the majority of 17q12 recurrent duplications are inherited from a parent who is often minimally affected or phenotypically normal, making the true penetrance difficult to ascertain.

Prevalence

In four studies of apparently unaffected controls, the 17q12 recurrent duplication was present in 1:2443 individuals [International Schizophrenia Consortium 2008, Itsara et al 2009, Shaikh et al 2009, Moreno-De-Luca et al 2010]. In a population study of 101,655 individuals from Iceland, the prevalence was 1:2,675 [Stefansson et al 2014].

In two different studies of individuals with intellectual disability, developmental delay or autism, the 17q12 recurrent duplication was reported in 5:2,034 (0.25%) individuals [Mitchell et al 2015] and 21:15,749 (0.13%) [Moreno-De-Luca et al 2010]; however, the frequency is much lower when accounting for all samples submitted in a clinical laboratory setting (19:22,231 [0.085%]) [Mitchell et al 2015].

In a cohort of individuals with schizophrenia, the 17q12 recurrent duplication was identified in 4:4,719 (0.08%) individuals [Szatkiewicz et al 2014].

Differential Diagnosis

The differential diagnosis of the 17q12 recurrent duplication is broad due to the clinical variability and the presence of relatively common abnormal phenotypes that occur in affected individuals including developmental delay, intellectual disability (ID), epilepsy, behavioral abnormalities, and microcephaly. All chromosome anomalies and genes known to be associated with ID (>200 have been identified; see OMIM Phenotypic Series: Autosomal dominant ID, Autosomal recessive ID, Nonsyndromic X-linked ID, and Syndromic X-linked ID) should be included in the differential diagnosis of the 17q12 recurrent duplication.

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with the 17q12 recurrent duplication, the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to diagnosis) are recommended.

Table 3.

Recommended Evaluations Following Initial Diagnosis in Individuals with 17q12 Recurrent Duplication

System/ConcernEvaluationComment
Constitutional Growth assessment
Development Developmental assessment
  • To incl motor, adaptive, cognitive, & speech/language eval
  • Eval for early intervention / special education
Psychiatric/
Behavioral
Neuropsychiatric evalIn persons age >12 mos: screen for behavior concerns incl sleep disturbances, ADHD, anxiety, &/or traits suggestive of ASD.
Neurologic Neurologic eval
  • To incl brain MRI
  • Consider EEG if seizures are a concern.
Gastrointestinal/
Feeding
Consultation w/gastroenterologist &/or feeding team for GI concerns, suspected dysphagia, or feeding difficulties
Eyes Ophthalmologic evalTo assess for ↓ vision, abnormal ocular movement, strabismus
Endocrine Assess for growth issues, dehydration, & signs/symptoms of diabetes or electrolyte disturbances.
Cardiovascular Echocardiogram
Renal Renal ultrasound exam
Genetic
counseling
By genetics professionals 1To inform affected persons & their families re nature, MOI, & implications of 17q12 recurrent duplication in order to facilitate medical & personal decision making
Family support/
resources
Assess need for:

ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder; GI = gastrointestinal; MOI = mode of inheritance

1.

Medical geneticist, certified genetic counselor, certified advanced genetic nurse

Treatment of Manifestations

Table 4.

Treatment of Manifestations in Individuals with 17q12 Recurrent Duplication

Manifestation/ConcernTreatmentConsiderations/Other
DD/ID See Developmental Delay / Intellectual Disability Management Issues.
Psychiatric/
behavioral disorders
Epilepsy Standardized treatment w/AEDs by experienced neurologist
  • Many AEDs may be effective; none has been demonstrated effective specifically for this disorder.
  • Education of parents/caregivers 1
Poor weight gain / Failure to thrive Feeding therapyLow threshold for clinical feeding eval &/or radiographic swallowing study if clinical signs or symptoms of dysphagia
Abnormal vision &/or strabismus Standard treatment(s) as recommended by ophthalmologistCommunity vision services through early intervention or school district
Central visual impairment No specific treatment; early intervention to stimulate visual development
Endocrine Treatment per endocrinologist
Cardiac anomalies Treatment per cardiologist
Renal anomalies Treatment per nephrologist
Family/Community
  • Ensure appropriate social work involvement to connect families w/local resources, respite, & support.
  • Coordinate care to manage multiple subspecialty appointments, equipment, medications, & supplies.
  • Ongoing assessment of need for palliative care involvement &/or home nursing
  • Consider involvement in adaptive sports or Special Olympics.

AED = antiepileptic drug; DD/ID = developmental delay / intellectual disability

1.

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 & My Child Toolkit.

Developmental Delay / Intellectual Disability Management Issues

The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.

Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.

Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.

All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:

  • Individualized education plan (IEP) services:
    • An IEP provides specially designed instruction and related services to children who qualify.
    • IEP services will be reviewed annually to determine whether any changes are needed.
    • Special education law requires that children participating in an IEP be in the least restrictive environment feasible at school and included in general education as much as possible, when and where appropriate.
    • Vision consultants should be a part of the child's IEP team to support access to academic material.
    • PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, privatesupportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.
    • As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.
  • A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.
  • Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.
  • Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.

Motor Dysfunction

Oral motor dysfunction should be assessed at each visit and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses, or feeding refusal that is not otherwise explained. Assuming that the child is safe to eat by mouth, feeding therapy (typically from an occupational or speech therapist) is recommended to help improve coordination or sensory-related feeding issues. Feeds can be thickened or chilled for safety. When feeding dysfunction is severe, an NG-tube or G-tube may be necessary.

Communication issues. Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication [AAC]) for individuals who have expressive language difficulties. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech, and in many cases can improve it.

Social/Behavioral Concerns

Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and typically performed one on one with a board-certified behavior analyst.

Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary.

Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist.

Surveillance

Table 5.

Recommended Surveillance for Individuals with 17q12 Recurrent Duplication

System/ConcernEvaluationFrequency
Development Monitor developmental progress & educational needs.At each visit
Psychiatric/
Behavioral
Behavioral assessment for anxiety, attention, & aggressive or self-injurious behavior
Neurologic
  • Assess for new seizures.
  • Monitor those w/seizures as clinically indicated.
Feeding
  • Measurement of growth parameters
  • Eval of nutritional status & safety of oral intake
Eyes Ophthalmology examFrequency as recommended by ophthalmologist
Endocrine Monitor for signs/symptoms of endocrinologic disorders; evaluate as needed.At each visit
Family/
Community
Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources) & care coordination.

Evaluation of Relatives at Risk

Consider genomic testing of sibs of a proband who is known to have the 17q12 recurrent duplication in order to refer sibs with a duplication promptly for close assessment/monitoring of developmental milestones in childhood and psychological issues through adulthood.

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.

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

The 17q12 recurrent duplication is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

  • About 90% of individuals with a 17q12 recurrent duplication inherited the genetic alteration from a parent. In many instances, the parent with the 17q12 recurrent duplication is phenotypically normal or minimally affected; in parents with features associated with the 17q12 recurrent duplication, reported manifestations range from mild cognitive impairment to learning difficulties, seizures, and mental illness.
  • The 17q12 recurrent duplication is de novo in approximately 10% of probands.
  • Genomic testing that will detect the 17q12 recurrent duplication present in the proband is recommended for the parents of the proband to confirm their genetic status and to allow reliable recurrence risk counseling.
  • If the 17q12 recurrent duplication identified in the proband is not identified in either confirmed biological parent, the following possibilities should be considered:

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 duplication identified in the proband, the risk to each sib of inheriting the duplication is 50%. It is not possible to predict the phenotype in sibs who inherit a 17q12 recurrent duplication because a wide spectrum of manifestations may be observed in family members with the duplication, ranging from no or mild cognitive impairment to learning difficulties, seizures, and mental illness.
  • If the 17q12 recurrent duplication identified in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is low (<1%) but greater than that of the general population because of the theoretic possibility of parental germline mosaicism.

Offspring of a proband. Each child of an individual with the 17q12 recurrent duplication has a 50% chance of inheriting the duplication; it is not possible to predict the phenotype in offspring who inherit the duplication.

Other family members. The risk to other family members depends on the genetic status of the proband’s parents: if a parent has the 17q12 recurrent duplication, his or her family members may also have the duplication.

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 are at risk of having a child with a 17q12 recurrent duplication.

Prenatal Testing and Preimplantation Genetic Testing

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

Pregnancies not known to be at increased risk for the 17q12 recurrent duplication. CMA performed in a pregnancy for other indications (e.g., advanced maternal age) may detect the recurrent 17q12 duplication.

Note: Regardless of whether a pregnancy is known or not known to be at increased risk for the 17q12 recurrent duplication, the prenatal finding of a 17q12 recurrent duplication cannot be used to predict the phenotype.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal 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.

  • 17q12 Foundation
    Email: chromosome17q12@gmail.com
  • Chromosome Disorder Outreach (CDO)
    PO Box 724
    Boca Raton FL 33429-0724
    Phone: 561-395-4252 (Family Helpline)
    Email: info@chromodisorder.org
  • Unique: The Rare Chromosome Disorder Support Group
    United Kingdom
    Phone: +44 (0) 1883 723356
    Email: info@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 Duplication: Genes and Databases

GeneChromosome LocusProteinClinVar
Not applicable 17q12Not applicable

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 Duplication (View All in OMIM)

614526CHROMOSOME 17q12 DUPLICATION SYNDROME

Molecular Pathogenesis

Duplication mechanism. The 17q12 recurrent duplication region is flanked by segmental duplications (low copy repeats) and is therefore susceptible to nonallelic homologous recombination (NAHR) [Sharp et al 2006]. The breakpoints of the recurrent duplication lie within the segmental duplication regions.

Genes of interest in this region. The 1.4-Mb 17q12 recurrent duplication contains 15 unique genes (AATF, ACACA, C17orf78, DDX52, DHRS11, DUSP14, GGNBP2, HNF1B, LHX1, MRM1, MYO19, PIGW, SYNRG, TADA2A, and ZNHIT3). It is not known which gene(s) may be responsible for the phenotypic features seen in individuals with the 17q12 recurrent duplication.

Pathogenic variants in (or deletion of) HNF1B are associated with renal cysts and diabetes syndrome, and pathogenic variants in LHX1 have been described in individuals with müllerian aplasia/Mayer-Rokitansky-Küster-Hauser syndrome. However, whether or how pathogenic variants in these genes contribute to phenotypes associated with the 17q12 recurrent duplication is unknown.

Chapter Notes

Author History

Heather C Mefford, MD, PhD (2016-present)
Elyse Mitchell, MS, CGC; Mayo Clinic (2016-2021)
Jennelle Hodge, PhD; Cedars-Sinai Medical Center (2016-2021)

Revision History

  • 13 January 2022 (aa) Revision: percentage of probands with duplications occurring de novo corrected to 10% in Genetic Counseling
  • 29 April 2021 (sw) Comprehensive update posted live
  • 25 February 2016 (bp) Review posted live
  • 5 October 2015 (jh) Original submission

References

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