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Juvenile Polyposis Syndrome

, MS, CGC, , MD, and , MD.

Author Information

Initial Posting: ; Last Update: February 3, 2022.

Estimated reading time: 29 minutes

Summary

Clinical characteristics.

Juvenile polyposis syndrome (JPS) is characterized by predisposition to hamartomatous polyps in the gastrointestinal (GI) tract, specifically in the stomach, small intestine, colon, and rectum. The term "juvenile" refers to the type of polyp rather than to the age of onset of polyps. Most individuals with JPS have some polyps by age 20 years; some may have only four or five polyps over their lifetime, whereas others in the same family may have more than 100. If the polyps are left untreated, they may cause bleeding and anemia. Most juvenile polyps are benign; however, malignant transformation can occur. Risk for GI cancers ranges from 11% to 86%. Most of this increased risk is attributed to colon cancer, but cancers of the stomach, upper GI tract, and pancreas have also been reported. A combined syndrome of JPS and hereditary hemorrhagic telangiectasia (HHT) is present in most individuals with an SMAD4 pathogenic variant.

Diagnosis/testing.

The diagnosis of JPS is established in a proband with any of the following: more than five juvenile polyps of the colorectum; multiple juvenile polyps throughout the GI tract; any number of juvenile polyps; and a family history of juvenile polyposis. Identification of a heterozygous pathogenic variant in SMAD4 or BMPR1A confirms the diagnosis if clinical features are inconclusive.

Management.

Treatment of manifestations: Colonoscopy with endoscopic polypectomy to reduce the risk of cancer, bleeding, and intestinal obstruction. When a large number of polyps are present, removal of all or part of the colon or stomach may be necessary. Iron replacement and red blood cell transfusion as needed for anemia; treatment as needed for manifestations of HHT, arteriovenous malformations, aortopathy, and/or valvular disease per cardiologist and cardiothoracic surgeon.

Surveillance: Assess for rectal bleeding, anemia, abdominal pain, constipation, diarrhea, or change in stool size, shape, and/or color at each visit; complete blood count as needed based on symptoms; colonoscopy and upper endoscopy every three years beginning at age 15 years or earlier if symptomatic or if polyps were present on the prior colonoscopy. For individuals following surgical resection: endoscopic evaluation of the remaining colon, rectum, and ileal pouch. In individuals with (or at risk for) SMAD4-related JPS, follow HHT surveillance guidelines and consider transthoracic echocardiogram.

Evaluation of relatives at risk: It is appropriate to evaluate apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from early surveillance and intervention. Evaluations include molecular genetic testing (if the pathogenic variant in the family is known) and gastrointestinal and hematologic evaluations if the pathogenic variant in the family is not known.

Genetic counseling.

JPS is inherited in an autosomal dominant manner. Up to half of individuals with JPS have an affected parent; approximately 50% of probands with JPS have no previous history of polyps in the family and may have the disorder as the result of a de novo pathogenic variant. Each child of an affected individual has a 50% chance of inheriting the pathogenic variant and developing JPS. Prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible if the pathogenic variant in the family is known.

GeneReview Scope

Juvenile Polyposis Syndrome: Included Phenotypes
  • Juvenile polyposis syndrome (JPS)
  • Juvenile polyposis syndrome / hereditary hemorrhagic telangiectasia (JPS/HHT)

For synonyms and outdated names see Nomenclature.

Diagnosis

Suggestive Findings

Juvenile polyposis syndrome (JPS) should be suspected in a proband with the following clinical and histopathologic features.

Clinical features

  • Anemia, rectal bleeding, or prolapse of rectal polyp
  • More than one juvenile polyp
  • One or more juvenile polyps and a family history of JPS

Note: "Juvenile" refers to the polyp histopathology, not the age of onset of polyps.

Histopathologic features. Juvenile polyps are hamartomas that develop from an abnormal collection of tissue elements normally present at this site. Juvenile polyps show a normal epithelium with a dense stroma, an inflammatory infiltrate, and a smooth surface with dilated, mucus-filled cystic glands in the lamina propria. Muscle fibers and the proliferative characteristics of adenomas are typically not seen in juvenile polyps.

Note: Variability in histopathology has been reported in polyps associated with juvenile polyposis syndrome / hereditary hemorrhagic telangiectasia (JPS/HHT) (see Clinical Characteristics) [Aretz et al 2007].

Establishing the Diagnosis

The diagnosis of JPS is established in a proband with any one of the following clinical features:

  • More than five juvenile polyps of the colon or rectum
  • Multiple juvenile polyps of the upper and lower gastrointestinal tract
  • Any number of juvenile polyps and a family history of juvenile polyposis
  • Identification of a heterozygous pathogenic variant in one of the genes listed in Table 1

Molecular genetic testing approaches can include BMPR1A and SMAD4 concurrent testing, serial single-gene testing, use of a multigene panel, and more comprehensive genomic testing.

Table 1.

Molecular Genetic Testing Used in Juvenile Polyposis Syndrome

Gene 1Proportion of JPS Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 2 Detectable by Method
Sequence analysis 3Gene-targeted deletion/duplication analysis 4
BMPR1A 28% 569%-85% 5, 615% 5
SMAD4 27% 583% 517% 5
Unknown 745%NA

NA = not applicable

1.
2.

See Molecular Genetics for information on variants detected in this gene.

3.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

4.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

5.
6.

Sequence analysis of the BMPR1A promoter region identified a pathogenic variant in 6/65 individuals with JPS who did not have a BMPR1A or SMAD4 pathogenic variant identified on sequencing of the coding regions or deletion/duplication testing [Calva-Cerqueira et al 2010]. Sequence analysis that includes the promoter region increases the proportion of pathogenic variants detected by sequencing.

7.

Two individuals with early-onset JPS have been found to have ENG pathogenic variants. Neither had clinical symptoms of HHT, which is known to be associated with ENG pathogenic variants; however, neither had yet reached the age at which symptoms of HHT commonly manifest [Sweet et al 2005, Howe et al 2007].

Clinical Characteristics

Clinical Description

Juvenile Polyposis Syndrome (JPS)

JPS is characterized by predisposition to hamartomatous polyps in the gastrointestinal (GI) tract, specifically in the stomach, small intestine, colon, and rectum. "Generalized juvenile polyposis" refers to polyps of the upper and lower GI tract. "Juvenile polyposis coli" refers to polyps of the colon only.

The polyps vary in size and shape: some are flat (sessile), whereas others have a stalk (pedunculated). The number of polyps in individuals with JPS varies. Some individuals may have only four or five polyps over their lifetime; others in the same family may have more than 100.

Bleeding may result from sloughing of the polyp or its surface epithelium with the passage of stool. If the polyps are left untreated, they may cause bleeding and anemia.

Juvenile polyps develop from infancy through adulthood. Most individuals with JPS have some polyps by age 20 years.

In juvenile polyposis of infancy, associated with a contiguous deletion of BMPR1A and PTEN, polyps develop within the first few years of life and are accompanied by hypoproteinemia, protein-losing enteropathy, diarrhea, anemia, anasarca, and failure to thrive [Taylor et al 2021].

Cancer risks associated with JPS. Most juvenile polyps are benign; however, malignant transformation can occur. Lifetime estimates of developing GI cancers in families with JPS range from 11% to 86%, with variability by region, time period included, and associated gene [Latchford et al 2012, Aytac et al 2015, Ishida et al 2018, Blatter et al 2020, MacFarland et al 2021]. In the largest study thus far of individuals with JPS caused by SMAD4/BMPR1A pathogenic variants, 15% of individuals developed cancer, which is consistent with other more recent studies [Blatter et al 2020]. Of individuals treated surgically and followed with surveillance, four of 27 individuals with SMAD4 pathogenic variants and none of eight individuals with BMPR1A pathogenic variants developed cancer [Aytac et al 2015]. Most of the increased risk is attributed to colorectal cancer; cancers of the stomach, upper GI tract, and pancreas have also been reported:

  • The incidence of colorectal cancer is 17%-22% by age 35 years and approaches 68% by age 60 years. The median age at diagnosis is 42 years.
  • The incidence of gastric cancer is 21% in those with gastric polyps.
  • The relative risk for colorectal cancer was 34.0% in individuals with JPS. The mean age of diagnosis of colorectal cancer was 43.9 years, with a cumulative lifetime risk of 38.7% [Brosens et al 2007].

Historically, the cancer incidence in one large family with a germline SMAD4 pathogenic variant suggested a lifetime risk for colorectal cancer of approximately 40%, and a lifetime risk for upper GI cancers of 20% [Howe et al 1998]. However, these cancer rates may change over time with the implementation of screening of young at-risk individuals and the removal of polyps before cancer develops.

Juvenile Polyposis Syndrome / Hereditary Hemorrhagic Telangiectasia (JPS/HHT)

Individuals with JPS/HHT have variable findings of juvenile polyposis and HHT (see Table 2). Most individuals with JPS who have an SMAD4 germline pathogenic variant have one or more clinical features of HHT. The findings of HHT may manifest in early childhood. A high frequency of pulmonary arteriovenous malformations (with digital clubbing) and epistaxis has been consistently noted in individuals with SMAD4-related HHT. Conversely, telangiectases do not appear to be a constant feature. Additional complications reported in individuals with JPS/HHT include anemia, migraine headaches, and exercise intolerance.

Table 2.

Clinical Features of SMAD4-Related Hereditary Hemorrhagic Telangiectasia

Clinical Feature% of Individuals w/Clinical FeatureAge of Onset
Epistaxis61%-71% 1, 2Childhood 3
Telangiectases57% 2Often after 30 yrs 4
Mucocutaneous telangiectases48% 35-65 yrs 3
Pulmonary AVM53%-81% 2, 3Birth-52 yrs 3
Hepatic AVM38% 321-52 yrs 3
Intracranial AVM4% 3Mean 11 yrs (±7 yrs) 1
Aortopathy38% 4Median 24 yrs (range 21-48 yrs) 5, 6
Intrapulmonary shunting on echocardiogram61% 35-59 yrs 3

AVM = arteriovenous malformation

1.
2.
3.

Wain et al [2014] reported the frequency of HHT-related symptoms in a cohort of 34 individuals with SMAD4 pathogenic variants.

4.
5.
6.

Thoracic aortic disease (e.g., aortic root dilatation, aneurysm, and aortic dissection) and mitral valve dysfunction have been reported in individuals with SMAD4 pathogenic variants [Heald et al 2015].

Expanding phenotype. There are reports of individuals with an SMAD4 pathogenic variant who also presented with retinitis pigmentosa, retinal detachment, joint laxity, and/or a marfanoid habitus. Data for these findings is limited and it is unclear if these are features of the SMAD4-related JPS/HHT phenotype. More work is needed to assess the frequency of these findings to determine medical management recommendations. Providers may wish to be aware of these reports and evaluate individuals on a case-by-case basis.

Genotype-Phenotype Correlations

Genotype-phenotype correlations in general are weak; family members with JPS and the same pathogenic variant can have a few polyps or more than 100. The age at which polyps develop can vary from the first decade to beyond the fourth decade among affected members of the same family. Some generalizations:

  • Individuals with SMAD4-related JPS are more likely to have a personal or family history of upper GI polyps than individuals with a BMPR1A pathogenic variant or those with no known pathogenic variant. The gastric phenotype in individuals with an SMAD4 pathogenic variant tends to be more aggressive with significant polyposis, anemia, and a higher risk for gastric cancer [Aytac et al 2015, Blatter et al 2020, MacFarland et al 2021]. Gastric cancer was reported almost exclusively in individuals with SMAD4-related JPS (27% of SMAD4-associated cancers vs 0% of BMPR1A-associated cancers) [Blatter et al 2020].
  • Colorectal cancer occurs more frequently than other cancers in BMPR1A-related JPS (88% of BMPR1A-associated cancers vs 58% of SMAD4-associated cancers) [Blatter et al 2020].
  • Individuals with either an SMAD4 or BMPR1A pathogenic variant are more likely than those without a pathogenic variant identified to have more than ten lower GI polyps and a family history of GI cancer [Burger et al 2002, Friedl et al 2002, Sayed et al 2002, MacFarland et al 2021]. They are also more likely to be older at diagnosis and at higher risk of requiring colectomy [MacFarland et al 2021].
  • There is some evidence that in individuals without a germline BMPR1A or SMAD4 pathogenic variant, polyp burden may decrease in adulthood and cancer risk may be lower [MacFarland et al 2021], but this requires further research.
  • JPS/HHT is associated with SMAD4 pathogenic variants.

Penetrance

One study evaluating 34 affected individuals with an SMAD4 pathogenic variant from 20 families revealed that 31/32 (97%) developed colonic polyps (diagnosed between ages 4 and 51 years), 21/31 (68%) developed gastric polyps, and 76% had some feature of HHT [Wain et al 2014]. In some instances, HHT-related symptoms in individuals with an SMAD4 pathogenic variant may be present prior to the onset of polyps [Author, personal observations]. Similar information is not available for individuals with a BMPR1A pathogenic variant. However, Aytac et al [2015] reported a similar colon and small bowel phenotype among individuals with an SMAD4 or BMPR1A pathogenic variant in the number and location of the polyps and surgical rates.

Nomenclature

Familial juvenile polyposis is an older term used to distinguish between simplex (i.e., a single affected individual in a family) and familial cases.

Prevalence

The incidence of JPS has been estimated to range between 1:16,000 and 1:100,000.

Differential Diagnosis

A juvenile polyp can result from genetic predisposition or chance. It should be noted that 1% to 2% of individuals in the general population develop a solitary juvenile polyp and do not meet diagnostic criteria for juvenile polyposis syndrome (JPS).

Genetic predisposition syndromes characterized by the presence of polyps are summarized in Table 3.

Table 3.

Polyp Predisposition Syndromes in the Differential Diagnosis of Juvenile Polyposis Syndrome

Gene(s) / Genetic MechanismDisorderMOIPolyp PhenotypeAdditional Characteristics
APC Familial adenomatous polyposis (See APC-Associated Polyposis Conditions.)ADGI polyposis; multiple adenomatous polypsOsteomas, dental anomalies, congenital hypertrophy of retinal pigment epithelium, desmoid tumors, thyroid cancer, risk of hepatoblastoma, medulloblastoma, & other assoc cancers
AXIN2 Polyposis & oligodontia (OMIM 608615)ADGI polyposis, adenomasAbsent teeth, colon cancer
GALNT12 Polyposis (OMIM 608812)ADGI polyposis, adenomaPreliminary evidence of assoc w/colon cancer
GREM1 overexpression 1Hereditary mixed polyposis syndrome (OMIM 601228)ADJuvenile polyps & multiple addl types of polyps: serrated, Peutz-Jeghers polyps, adenomas

Significant colorectal cancer risk

MLH1
MSH2
MSH6
PMS2
EPCAM
Lynch syndrome ADColorectal polyps; few adenomatous polypsSignificant colorectal cancer risk; cancers of endometrium, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, &skin
MLH1
MSH2
MSH6
PMS2
Constitutional mismatch repair deficiency (See Lynch Syndrome, Molecular Genetics.)ARColorectal polyps, many early onset adenomatous polypsSignificant cancer risk starting in early childhood incl brain tumors, leukemias/lymphomas, & colon cancers
MSH3 Polyposis (OMIM 617100)ARGI polyposis, adenomasColon cancer
MUTYH MUTYH-associated polyposis ARGI polyposis; multiple colonic adenomatous polyps; duodenal adenomas; additional types of polyps: serrated, hyperplastic/sessile serrated, mixedSignificant colorectal cancer risk; cancers of duodenum, stomach, ovary, & bladder
NTHL1 Polyposis (OMIM 616415)ARGI polyposis, adenomasColon cancer
PTCH1
SUFU
Nevoid basal cell carcinoma syndrome ADGastric polypsMultiple jaw keratocysts, basal cell carcinoma, macrocephaly, frontal bossing, coarse facial features, facial milia
PTEN PTEN hamartoma tumor syndrome ADVariable polyp types, mainly hamartomatous polyps incl juvenile polyps, also tubular adenomas, ganglioneuromas, serrated polypsBenign & malignant tumors of thyroid, breast, & endometrium; vascular malformations; ASD, DD; macrocephaly, trichilemmomas, papillomatous papules, lipomas, pigmented macules of glans penis
RNF43 Serrated polyposis syndrome (OMIM 617108)ADGI polyposis, hyperplastic, sessile serrated adenomas, adenomasColon cancer
STK11 Peutz-Jeghers syndrome ADGI polyposis; polyps have smooth muscle hyperplasia as prominent feature.Mucocutaneous pigmentation cancer risk incl breast, colon, pancreatic, ovarian, stomach, lung, & small intestine

AD = autosomal dominant; AR = autosomal recessive; ASD = autism spectrum disorder; DD = developmental delay; GI = gastrointestinal; MOI = mode of inheritance

1.

Duplications of 15q13-q14 lead to overexpression of GREM1.

ACVRL1-, ENG-, and GDF2-related hereditary hemorrhagic telangiectasia and other genes associated with vascular dysplasia syndromes including EPHB4 and RASA1 (see Capillary Malformation-Arteriovenous Malformation Syndrome) can be considered in the differential diagnosis of individuals with gastrointestinal bleeding and anemia who do not have polyposis.

Management

Clinical practice guidelines for juvenile polyposis syndrome have been published [Achatz et al 2017, Cohen et al 2019, NCCN 2021].

Evaluations Following Initial Diagnosis

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

Table 4.

Recommended Evaluations Following Initial Diagnosis in Individuals with Juvenile Polyposis Syndrome

System/ConcernEvaluationComment
Gastrointestinal Assess for abdominal pain, rectal bleeding, constipation, diarrhea, or change in stool size, shape, &/or color.At diagnosis
  • Complete blood count
  • Colonoscopy
  • Upper endoscopy
By age 15 yrs or earlier if symptomatic
Hematologic/
Cardiovascular
  • Evaluate for complications related to HHT.
  • Consider transthoracic echocardiogram.
  • At diagnosis in those w/SMAD4 pathogenic variant
  • Note: Recommended age at first transthoracic echocardiogram has not been determined.
Genetic
counseling
By genetics professionals 1To inform affected persons & their families re nature, MOI, & implications of JPS to facilitate medical & personal decision making

HHT = hereditary hemorrhagic telangiectasia; MOI = mode of inheritance

1.

Medical geneticist, certified genetic counselor, certified advanced genetic nurse

Treatment of Manifestations

Table 5.

Treatment of Manifestations in Individuals with Juvenile Polyposis Syndrome

Manifestation/
Concern
TreatmentConsiderations/Other
GI polyps Colonoscopy w/endoscopic polypectomyTo ↓ morbidity by ↓ risk for cancer, bleeding, or intestinal obstruction
  • Partial or total gastrectomy
  • Partial or total colectomy (subtotal colectomy w/ileorectal anastomosis or proctocolectomy w/ileoanal pouch) 1
May be necessary in those w/many polyps to alleviate symptoms &/or ↓ cancer risk
Anemia
  • Iron replacement (oral or parenteral if needed)
  • Red blood cell transfusion as needed
May be improved by polypectomy or surgery (gastrectomy/colectomy)
GI bleeding See Hereditary Hemorrhagic Telangiectasia, Management.In those w/SMAD4 pathogenic variant
Epistaxis
AVMs/
Aortopathy/
Valvular disease
Treatment per cardiologist & cardiothoracic surgeon

AVM = arteriovenous malformation; GI = gastrointestinal

1.

The preferred procedure is debated. The number of colonic or rectal polyps does not appear to correlate with the need for proctectomy [Oncel et al 2005].

Surveillance

The surveillance recommended in Table 6 is for individuals with an SMAD4 or BMPR1A pathogenic variant identified by molecular genetic testing, individuals with a clinical diagnosis of JPS, or individuals with a family history of JPS who have not undergone molecular genetic testing or whose molecular genetic test results were uninformative.

Table 6.

Recommended Surveillance for Individuals with Juvenile Polyposis Syndrome

System/ConcernEvaluationFrequency
Gastrointestinal Assess for rectal bleeding, anemia, abdominal pain, constipation, diarrhea, or change in stool size, shape, &/or color.At each visit
Complete blood countAs needed based on symptoms
  • Colonoscopy
  • Upper endoscopy
  • Note: Following surgical bowel resection, continue screening for polyps in remaining colon, rectum, & ileal pouch.
  • Every 3 yrs beginning at age 15 yrs or earlier if symptomatic
  • If polyps are found: following polyp treatment, annual screening until no polyps are found, then screening every 3 yrs
  • In those w/o germline SMAD4 or BMPR1A pathogenic variant: every 5 yrs in adulthood if no polyps are found
Hematologic / Cardiovascular Note: To date, frequency of echocardiography monitoring for aortopathy has not been determined. 1

Agents/Circumstances to Avoid

SMAD4-related HHT

  • Individuals with significant epistaxis are advised to avoid vigorous nose blowing, lifting of heavy objects, straining during bowel movements, and finger manipulation in the nose. Some individuals with HHT experience increased epistaxis after drinking alcohol.
  • Most otolaryngologists with experience treating individuals with HHT advise against electric and chemical cautery and transcatheter embolotherapy for treatment of recurrent nosebleeds.
  • Anticoagulants including aspirin and nonsteroidal anti-inflammatory agents such as ibuprofen that interfere with normal clotting should be avoided unless required for treatment of other medical conditions. In one study, lower-dose agents, particularly anti-platelet agents, were not associated with hemorrhage in a high proportion of affected individuals. The findings support the use of antiplatelet or anticoagulant agents, with caution, if there is a very strong indication for their use [Devlin et al 2013].
  • Scuba diving should be avoided unless contrast echocardiography performed within the last five years was negative for evidence of a right-to-left shunt.
  • Liver biopsy should be avoided [Buscarini et al 2006].

Evaluation of Relatives at Risk

It is appropriate to evaluate apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from early surveillance and intervention.

In families in which findings suggest JPS or families with a known BMPR1A pathogenic variant, evaluations can include:

  • Molecular genetic testing at or prior to age 15 years if the pathogenic variant in the family is known;
  • If the familial pathogenic variant is not known, complete blood count (CBC) and lower intestinal endoscopy in individuals age 15 years an older. Normal results do not rule out a diagnosis of JPS (see Surveillance for additional recommendations).

In families in which findings suggest juvenile polyposis syndrome / hereditary hemorrhagic telangiectasia (JPS/HHT) or families with a known SMAD4 pathogenic variant:

  • Molecular genetic testing before age 15 years for children at risk for a known familial SMAD4 pathogenic variant should be offered because the surveillance for HHT-related findings begins earlier in childhood than the surveillance for polyps.
  • In families in which findings suggest JPS/HHT but the familial pathogenic variant is not known:
    • CBC and lower intestinal endoscopy in individuals age 15 years an older, or earlier if symptoms of polyposis. Normal results do not rule out a diagnosis of JPS (see Surveillance for additional recommendations).
    • In individuals older than age 40 years, targeted medical history and clinical examination for features of HHT. The absence of mild but recurrent epistaxis and subtle telangiectases in characteristic locations on careful examination is reassuring (see Hereditary Hemorrhagic Telangiectasia).
    • In individuals age 40 years and younger, targeted medical history and clinical examination for features of HHT as well as initial evaluation for brain and pulmonary arteriovenous malformations, as features of HHT may not be identified by medical history and clinical examination in younger individuals

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

Therapies Under Investigation

In individuals with juvenile polyposis of infancy due to deletion of both BMPR1A and PTEN, sirolimus has been investigated as an intervention to decrease polyp burden [Busoni et al 2019]. In a small case series, sirolimus therapy reduced symptoms including bleeding and enteropathy, and also reduced rate of colectomy [Taylor et al 2021].

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.

Other

No known chemoprevention options are effective for juvenile polyps.

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

Juvenile polyposis syndrome (JPS) is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

  • Up to half of individuals diagnosed with JPS have an affected parent.
  • Approximately 50% of individuals diagnosed with JPS have no previous history of polyps in the family and may have the disorder as the result of a de novo pathogenic variant [Restrepo et al 1978, Coburn et al 1995].
  • If the proband appears to be the only affected family member (i.e., a simplex case), evaluation of the parents is recommended in order to clarify their genetic/clinical status and to assess the risk of JPS in sibs and other relatives. Recommendations for the evaluation of parents of a proband include the following:
  • If the proband has a known pathogenic variant that cannot be identified in either parent and parental identified testing has confirmed biological maternity and paternity, the following possibilities should be considered:
  • The family history of some individuals diagnosed with JPS may appear to be negative because of failure to recognize the disorder in family members, reduced penetrance and variable expressivity, early death of the parent before the onset of symptoms, or late onset of the disease in the affected parent. Therefore, an apparently negative family history cannot be confirmed unless appropriate clinical evaluation and/or appropriate molecular genetic testing has been performed on the parents of the proband.

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

  • If a parent of the proband is affected and/or is known to have the pathogenic variant identified in the proband, the risk to the sibs of inheriting the pathogenic variant is 50%.
  • Intrafamilial variability (including variable symptoms, ages of onset, and cancer risks) has been reported among family members who are heterozygous for the same SMAD4 or BMPR1A pathogenic variant.
  • If the proband has a known JPS-causing pathogenic variant that cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is slightly greater than that of the general population because of the possibility of parental germline mosaicism [Lamireau et al 2005].
  • If the genetic status of the parents is unknown (and/or a molecular diagnosis has not been established in the proband), sibs should be considered at risk for JPS (regardless of whether parents have had manifestations of the disorder) and offered molecular genetic testing and screening/surveillance for JPS (and HHT if findings in the proband suggest JPS/HHT).

Offspring of a proband. Each child of an individual with JPS has a 50% chance of inheriting the causative pathogenic variant and having an increased risk of developing JPS.

Other family members. The risk to other family members depends on the genetic status of the proband's parents: if a parent is affected and/or is known to have the pathogenic variant identified in the proband, his or her family members may be at risk and may benefit from molecular genetic testing and/or surveillance.

Related Genetic Counseling Issues

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

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 affected or at risk.

Genetic cancer risk assessment and counseling. For a comprehensive description of the medical, psychosocial, and ethical ramifications of identifying at-risk individuals through cancer risk assessment with or without molecular genetic testing, see Cancer Genetics Risk Assessment and Counseling – for health professionals (part of PDQ®, National Cancer Institute).

Molecular genetic testing of asymptomatic individuals younger than age 18 years. If the JPS-causing pathogenic variant has been identified in a family, predictive molecular genetic testing can be used to identify family members who would benefit from early screening.

  • Families with a known BMPR1A pathogenic variant. Since surveillance for asymptomatic individuals at risk for JPS is recommended beginning at age 15 years, it is appropriate to consider predictive genetic testing for JPS around this age or earlier. If parents are concerned about their child's ability to cope with the significance of test results, the disclosure of the molecular genetic testing information, but not surveillance, can be delayed.
    If symptoms of JPS appear before age 15 years, surveillance should begin at that time and disclosure of molecular genetic test results may be a reasonable option. It is important to consider the risks and benefits for children of learning this information at a young age and to consider ways to discuss this information with children and to answer their questions.
  • Families with a known SMAD4 pathogenic variant. Predictive molecular genetic testing before age 15 years should be offered because the surveillance for HHT-related findings begins earlier in childhood (see Hereditary Hemorrhagic Telangiectasia) than the surveillance for polyps.

See Management, Evaluation of Relatives at Risk for recommended evaluations of at-risk relatives when the familial pathogenic variant is not known.

DNA banking. Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown).

Prenatal Testing and Preimplantation Genetic Testing

Once the JPS-causing pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for JPS are possible.

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.

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.

Juvenile Polyposis Syndrome: Genes and Databases

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 Juvenile Polyposis Syndrome (View All in OMIM)

174900JUVENILE POLYPOSIS SYNDROME; JPS
175050JUVENILE POLYPOSIS/HEREDITARY HEMORRHAGIC TELANGIECTASIA SYNDROME; JPHT
600993SMAD FAMILY MEMBER 4; SMAD4
601299BONE MORPHOGENETIC PROTEIN RECEPTOR, TYPE IA; BMPR1A

Molecular Pathogenesis

The mechanism of juvenile polyp formation as a consequence of germline pathogenic variants in SMAD4 or BMPR1A is not known. Although SMAD4 is a tumor suppressor gene, loss of heterozygosity has not been definitively demonstrated to cause polyp development. Furthermore, whether such changes would affect cells in the epithelium, the lamina propria, or both is also not known. BMPR1A is not known to be a tumor suppressor gene, although few studies have examined it in cancer.

SMAD4 is the common intracellular mediator of the TGF-β superfamily signaling pathways. BMPR1A encodes a type I cell surface receptor for the BMP pathway. Ligands, such as TGF-β or BMP, bind to a receptor and activate signaling pathways involving regulatory SMAD proteins, which form protein complexes with SMAD4 that migrate to the nucleus and bind directly to DNA sequences to regulate transcription [Heldin et al 1997, Gómez Pinto et al 2018]. The downstream genes under the control of these signaling pathways are still being actively investigated.

Most BMPR1A pathogenic variants occur in the protein kinase domain and occasionally in the cysteine-rich region of the extracellular domain. No pathogenic variants have been described in the transmembrane domain [Howe et al 2004]. In vitro studies have shown that proteins resulting from JPS-related BMPR1A pathogenic missense variants are retained in the cytoplasm and do not traffic to the cell membrane like the wild type protein [Howe et al 2013].

Most SMAD4 pathogenic variants occur in the MH2 domain, which plays an important role for nuclear localization, interaction with other SMAD proteins, and transcriptional activation. In vitro studies demonstrate that pathogenic nonsense variants lead to significantly reduced bone morphogenetic protein signaling, with less of an effect for missense variants [Carr et al 2012].

Mechanism of disease causation. Unknown

Cancer and Benign Tumors

Somatic SMAD4 variants that are not present in the germline have been reported in colorectal, pancreatic, and prostate cancers occurring as single tumors in the absence of any other findings of juvenile polyposis syndrome [Chen et al 2014, McCarthy & Chetty 2018].

Chapter Notes

Author Notes

Dr James R Howe is a surgical oncologist and primary researcher in the field of juvenile polyposis syndrome. Joy Larsen Haidle is a genetic counselor with the Cancer Genetics program at North Memorial Health Cancer Center who is actively involved in the development of genetic counseling guidelines with Dr Howe's research program.

Dr Suzanne P MacFarland is a pediatric oncologist and cancer predisposition researcher in the field of juvenile polyposis syndrome. She runs a multidisciplinary polyposis clinic at the Children's Hospital of Philadelphia.

Revision History

  • 3 February 2022 (sw) Comprehensive update posted live
  • 9 March 2017 (sw) Comprehensive update posted live
  • 3 December 2015 (jrh) Revision: corrections to Genetically Related Disorders
  • 22 May 2014 (me) Comprehensive update posted live
  • 29 September 2011 (me) Comprehensive update posted live
  • 9 September 2008 (me) Comprehensive update posted live
  • 22 February 2007 (cd) Revision: prenatal diagnosis available for BMPR1A mutations
  • 2 November 2006 (cd) Revision: prenatal diagnosis available for SMAD4 mutations
  • 13 June 2005 (me) Comprehensive update posted live
  • 20 May 2004 (cd) Revision: Genetic Counseling
  • 27 October 2003 (cd) Revision: Statements and Policies
  • 13 May 2003 (me) Review posted live
  • 4 January 2003 (jrh) Original submission

References

Published Guidelines / Consensus Statements

  • Achatz MI, Porter CC, Brugières L, Druker H, Frebourg T, Foulkes WD, Kratz CP, Kuiper RP, Hansford JR, Hernandez HS, Nathanson KL, Kohlmann WK, Doros L, Onel K, Schneider KW, Scollon SR, Tabori U, Tomlinson GE, Evans DGR, Plon SE. Cancer screening recommendations and clinical management of inherited gastrointestinal cancer syndromes in childhood. Clin Cancer Res. 2017;23:e107–14. [PubMed: 28674119]
  • Cohen S, Hyer W, Mas E, Auth M, Attard TM, Spalinger J, Latchford A, Durno C. Management of juvenile polyposis syndromes in children and adolescents: a position paper from the ESPGHAN Polyposis Working Group. J Pediatr Gastroenterol Nutr. 2019;68:453–62. [PubMed: 30585890]
  • Committee on Bioethics, Committee on Genetics, and American College of Medical Genetics and Genomics Social, Ethical, Legal Issues Committee. Ethical and policy issues in genetic testing and screening of children. Available online. 2013. Accessed 1-26-22.
  • Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL, et al. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2015;17:70–87. [PubMed: 25394175]
  • NCCN. Genetic/Familial High-Risk Assessment: Colorectal. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines). Version 1.2021 (May 11, 2021). Available online. Registration required. 2021.

Literature Cited

  • Achatz MI, Porter CC, Brugières L, Druker H, Frebourg T, Foulkes WD, Kratz CP, Kuiper RP, Hansford JR, Hernandez HS, Nathanson KL, Kohlmann WK, Doros L, Onel K, Schneider KW, Scollon SR, Tabori U, Tomlinson GE, Evans DGR, Plon SE. Cancer screening recommendations and clinical management of inherited gastrointestinal cancer syndromes in childhood. Clin Cancer Res. 2017;23:e107–e114. [PubMed: 28674119]
  • Alimi A, Weeth-Feinstein LA, Stettner A, Caldera F, Weiss JM. Overlap of Juvenile polyposis syndrome and Cowden syndrome due to de novo chromosome 10 deletion involving BMPR1A and PTEN: implications for treatment and surveillance. Am J Med Genet A. 2015;167:1305–8. [PMC free article: PMC4449295] [PubMed: 25846706]
  • Aretz S, Stienen D, Uhlhaas S, Stolte M, Entius MM, Loff S, Back W, Kaufmann A, Keller KM, Blaas SH, Siebert R, Vogt S, Spranger S, Holinski-Feder E, Sunde L, Propping P, Friedl W. High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome. J Med Genet. 2007;44:702–9. [PMC free article: PMC2752176] [PubMed: 17873119]
  • Aytac E, Sulu B, Heald B, O'Malley M, LaGuardia L, Remzi FH, Kalady MF, Burke CA, Church JM. Genotype-defined cancer risk in juvenile polyposis syndrome. Br J Surg. 2015;102:114–8. [PubMed: 25389115]
  • Blatter R, Tschupp B, Aretz S, Bernstein I, Colas C, Evans DG, Genuardi M, Hes FJ, Hüneburg R, Järvinen H, Lalloo F, Moeslein G, Renkonen-Sinisalo L, Resta N, Spier I, Varvara D, Vasen H, Latchford AR, Heinimann K. Disease expression in juvenile polyposis syndrome: a retrospective survey on a cohort of 221 European patients and comparison with a literature-derived cohort of 473 SMAD4/BMPR1A pathogenic variant carriers. Genet Med. 2020;22:1524–32. [PMC free article: PMC7462743] [PubMed: 32398773]
  • Breckpot J, Tranchevent LC, Thienpont B, Bauters M, Troost E, Gewillig M, Vermeesch JR, Moreau Y, Devriendt K, Van Esch H. BMPR1A is a candidate gene for congenital heart defects associated with the recurrent 10q22q23 deletion syndrome. Eur J Med Genet. 2012;55:12–6. [PubMed: 22067610]
  • Brosens LA, van Hattem A, Hylind LM, Iacobuzio-Donahue C, Romans KE, Axilbund J, Cruz-Correa M, Tersmette AC, Offerhaus GJ, Giardiello FM. Risk of colorectal cancer in juvenile polyposis. Gut. 2007;56:965–7. [PMC free article: PMC1994351] [PubMed: 17303595]
  • Burger B, Uhlhaas S, Mangold E, Propping P, Friedl W, Jenne D, Dockter G, Back W. Novel de novo mutation of MADH4/SMAD4 in a patient with juvenile polyposis. Am J Med Genet. 2002;110:289–91. [PubMed: 12116240]
  • Buscarini E, Plauchu H, Garcia Tsao G, White RI Jr, Sabbà C, Miller F, Saurin JC, Pelage JP, Lesca G, Marion MJ, Perna A, Faughnan ME. Liver involvement in hereditary hemorrhagic telangiectasia: consensus recommendations. Liver Int. 2006;26:1040–6. [PubMed: 17032403]
  • Busoni VB, Orsi M, Lobos PA, D'Agostino D, Wagener M, De la Iglesia P, Fox VL. Successful treatment of juvenile polyposis of infancy with sirolimus. Pediatrics. 2019;144:e20182922. [PubMed: 31366686]
  • Calva-Cerqueira D, Chinnathambi S, Pechman B, Bair J, Larsen-Haidle J, Howe JR. The rate of germline mutations and large deletions of SMAD4 and BMPR1A in juvenile polyposis. Clin Genet. 2009;75:79–85. [PubMed: 18823382]
  • Calva-Cerqueira D, Dahdaleh FS, Woodfield G, Chinnathambi S, Nagy PL, Larsen-Haidle J, Weigel RJ, Howe JR. Discovery of the BMPR1A promoter and germline mutations that cause juvenile polyposis. Hum Mol Genet. 2010;19:4654–62. [PMC free article: PMC2972697] [PubMed: 20843829]
  • Cao X, Eu KW, Kumarasinghe MP, Li HH, Loi C, Cheah PY. Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high-density single nucleotide polymorphism (SNP) scan and identification of BMPR1A loss of function. J Med Genet. 2006;43:e13. [PMC free article: PMC2563243] [PubMed: 16525031]
  • Carr JC, Dahdaleh FS, Wang D, Howe JR. Germline mutations in SMAD4 disrupt bone morphogenetic protein signaling. J Surg Res. 2012;174:211–4. [PMC free article: PMC3418515] [PubMed: 22316667]
  • Cheah PY, Wong YH, Chau YP, Loi C, Lim KH, Lim JF, Koh PK, Eu KW. Germline bone morphogenesis protein receptor 1A mutation causes colorectal tumorigenesis in hereditary mixed polyposis syndrome. Am J Gastroenterol. 2009;104:3027–33. [PubMed: 19773747]
  • Chen YW, Hsiao PJ, Weng CC, Kuo KK, Kuo TL, Wu DC, Hung WC, Cheng KH. SMAD4 loss triggers the phenotypic changes of pancreatic ductal adenocarcinoma cells. BMC Cancer. 2014;14:181. [PMC free article: PMC4007528] [PubMed: 24625091]
  • Coburn MC, Pricolo VE, DeLuca FG, Bland KI. Malignant potential in intestinal juvenile polyposis syndromes. Ann Surg Oncol. 1995;2:386–91. [PubMed: 7496832]
  • Cohen S, Hyer W, Mas E, Auth M, Attard TM, Spalinger J, Latchford A, Durno C. Management of juvenile polyposis syndromes in children and adolescents: a position paper from the ESPGHAN Polyposis Working Group. J Pediatr Gastroenterol Nutr. 2019;68:453–62. [PubMed: 30585890]
  • Dahdaleh FS, Carr JC, Calva D, Howe JR. Juvenile polyposis and other intestinal polyposis syndromes with microdeletions of chromosome 10q22-23. Clin Genet. 2012;81:110–6. [PMC free article: PMC3236803] [PubMed: 21834858]
  • Delnatte C, Sanlaville D, Mougenot JF, Vermeesch JR, Houdayer C, Blois MC, Genevieve D, Goulet O, Fryns JP, Jaubert F, Vekemans M, Lyonnet S, Romana S, Eng C, Stoppa-Lyonnet D. Contiguous gene deletion within chromosome arm 10q is associated with juvenile polyposis of infancy, reflecting cooperation between the BMPR1A and PTEN tumor-suppressor genes. Am J Hum Genet. 2006;78:1066–74. [PMC free article: PMC1474102] [PubMed: 16685657]
  • Devlin HL, Hosman AE, Shovlin CL. Antiplatlet and anticoagulant agents in hereditary hemorrhagic telangiectasia. N Engl J Med. 2013;368:876–8. [PubMed: 23445111]
  • Friedl W, Uhlhaas S, Schulmann K, Stolte M, Loff S, Back W, Mangold E, Stern M, Knaebel HP, Sutter C, Weber RG, Pistorius S, Burger B, Propping P. Juvenile polyposis: massive gastric polyposis is more common in MADH4 mutation carriers than in BMPR1A mutation carriers. Hum Genet. 2002;111:108–11. [PubMed: 12136244]
  • Gómez Pinto LI, Rodriguez D, Adamo AM, Mathieu PA. TGF-β pro-oligodendrogenic effects on adult SVZ progenitor cultures and its interaction with the Notch signaling pathway. Glia. 2018;66:396–412. [PubMed: 29076551]
  • Heald B, Rigelsky C, Moran R, LaGuardia L, O'Malley M, Burke CA, Zahka K. Prevalence of thoracic aortopathy in patients with juvenile polyposis syndrome-hereditary hemorrhagic telangiectasia due to SMAD4. Am J Med Genet. 2015;167A:1758–62. [PubMed: 25931195]
  • Heldin CH, Miyazono K, ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature. 1997;390:465–71. [PubMed: 9393997]
  • Howe JR, Haidle JL, Lal G, Bair J, Song C, Pechman B, Chinnathambi S, Lynch HT. ENG mutations in MADH4.BMPR1A mutation negative patients with juvenile polyposis. Clin Genet. 2007;71:91–2. [PubMed: 17204053]
  • Howe JR, Roth S, Ringold JC, Summers RW, Jarvinen HJ, Sistonen P, Tomlinson IP, Houlston RS, Bevan S, Mitros FA, Stone EM, Aaltonen LA. Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science. 1998;280:1086–8. [PubMed: 9582123]
  • Howe JR, Sayed MG, Ahmed AF, Ringold J, Larsen-Haidle J, Merg A, Mitros FA, Vaccaro CA, Petersen GM, Giardiello FM, Tinley ST, Aaltonen LA, Lynch HT. The prevalence of MADH4 and BMPR1A mutations in juvenile polyposis and absence of BMPR2, BMPR1B, and ACVR1 mutations. J Med Genet. 2004;41:484–91. [PMC free article: PMC1735829] [PubMed: 15235019]
  • Howe JR, Dahdaleh FS, Carr JC, Wang D, Sherman SK, Howe JR. BMPR1A mutations in juvenile polyposis affect cellular localization. J Surg Res. 2013;184:739–45. [PMC free article: PMC3683109] [PubMed: 23433720]
  • Ishida H, Ishibashi K, Iwama T. Malignant tumors associated with juvenile polyposis syndrome in Japan. Surg Today. 2018;48:253–63. [PubMed: 28550623]
  • Jelsig AM, Tørring PM, Kjeldsen AD, Qvist N, Bojesen A, Jensen UB, Andersen MK, Gerdes AM, Brusgaard K, Ousager LB. JP-HHT phenotype in Danish patients with SMAD4 mutations. Clin Genet. 2016;90:55–62. [PubMed: 26572829]
  • Lamireau T, Olschwang S, Rooryck C, Le Bail B, Chateil JF, Lacombe D. SMAD4 germinal mosaicism in a family with juvenile polyposis and hypertrophic osteoarthropathy. J Pediatr Gastroenterol Nutr. 2005;41:117–20. [PubMed: 15990641]
  • Latchford AR, Neale K, Phillips RK, Clark SK. Juvenile polyposis syndrome: a study of genotype, phenotype, and long-term outcome. Dis Colon Rectum. 2012;55:1038–43. [PubMed: 22965402]
  • Lin AE, Alali A, Starr LJ, Shah N, Beavis A, Pereira EM, Lindsay ME, Klugman S. Gain-of-function pathogenic variants in SMAD4 are associated with neoplasia in Myhre syndrome. Am J Med Genet A. 2020;182:328–37. [PubMed: 31837202]
  • MacFarland SP, Ebrahimzadeh JE, Zelley K, Begum L, Bass LM, Brand RE, Dudley B, Fishman DS, Ganzak A, Karloski E, Latham A, Llor X, Plon S, Riordan MK, Scollon SR, Stadler ZK, Syngal S, Ukaegbu C, Weiss JM, Yurgelun MB, Brodeur GM, Mamula P, Katona BW. Phenotypic differences in juvenile polyposis syndrome with or without a disease-causing SMAD4/BMPR1A variant. Cancer Prev Res (Phila). 2021;14:215–22. [PMC free article: PMC8557953] [PubMed: 33097490]
  • McCarthy AJ, Chetty R. Smad4/DPC4. J Clin Pathol. 2018;71:661–4. [PubMed: 29720405]
  • Miyahara Y, Ishida H, Kawabe K, Eto H, Kasai T, Ito T, Kaneko K, Arai M, Kamae N, Momose S, Eguchi H, Okazaki Y. A novel germline BMPR1A variant (c.72_73delGA) in a Japanese family with hereditary mixed polyposis syndrome. Jpn J Clin Oncol. 2020;50:826–9. [PMC free article: PMC7345204] [PubMed: 32378721]
  • NCCN. Genetic/Familial High-Risk Assessment: Colorectal. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines). Version 1.2021 (May 11, 2021). Available online. Registration required. 2021.
  • Nishida T, Faughnan ME, Krings T, Chakinala M, Gossage JR, Young WL, Kim H, Pourmohamad T, Henderson KJ, Schurm SD, James M, Quinnine N, Bharatha A, Terbrugge KG, White RI Jr. Brain arteriovenous malformations associated with hereditary hemorrhagic telangiectasia: gene-phenotype correlations. Am J Med Genet A. 2012;158A:2829–34. [PMC free article: PMC3610331] [PubMed: 22991266]
  • Oliveira PH, Cunha C, Almeida S, Ferreira R, Maia S, Saraiva JM, Lopes MF. Juvenile polyposis of infancy in a child with deletion of BMPR1A and PTEN genes: surgical approach. J Pediatr Surg. 2013;48:e33–7. [PubMed: 23331837]
  • Oncel M, Church JM, Remzi FH, Fazio VW. Colonic surgery in patients with juvenile polyposis syndrome: a case series. Dis Colon Rectum. 2005;48:49–55. [PubMed: 15690657]
  • O'Malley M, LaGuardia L, Kalady MF, Parambil J, Heald B, Eng C, Church J, Burke CA. The prevalence of hereditary hemorrhagic telangiectasia in juvenile polyposis syndrome. Dis Colon Rectum. 2012;55:886–92. [PubMed: 22810475]
  • O'Riordan JM, O'Donoghue D, Green A, Keegan D, Hawkes LA, Payne SJ, Sheahan K, Winter DC. Hereditary mixed polyposis syndrome due to a BMPR1A mutation. Colorectal Dis. 2010;12:570–3. [PubMed: 19438883]
  • Restrepo C, Moreno J, Duque E, Cuello C, Amsel J, Correa P. Juvenile colonic polyposis in Colombia. Dis Colon Rectum. 1978;21:600–12. [PubMed: 738175]
  • Russell BE, Rigueur D, Weaver KN, Sund K, Basil JS, Hufnagel RB, Prows CA, Oestreich A, Al-Gazali L, Hopkin RJ, Saal HM, Lyons K, Dauber A. Homozygous missense variant in BMPR1A resulting in BMPR signaling disruption and syndromic features. Mol Genet Genomic Med. 2019;7:e969. [PMC free article: PMC6825850] [PubMed: 31493347]
  • Salviati L, Patricelli M, Guariso G, Sturniolo GC, Alaggio R, Bernardi F, Zuffardi O, Tenconi R. Deletion of PTEN and BMPR1A on chromosome 10q23 is not always associated with juvenile polyposis of infancy. Am J Hum Genet. 2006;79:593–6. [PMC free article: PMC1559543] [PubMed: 16909400]
  • Sayed MG, Ahmed AF, Ringold JR, Anderson ME, Bair JL, Mitros FA, Lynch HT, Tinley ST, Petersen GM, Giardiello FM, Vogelstein B, Howe JR. Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis. Ann Surg Oncol. 2002;9:901–6. [PubMed: 12417513]
  • Sweet K, Willis J, Zhou XP, Gallione C, Sawada T, Alhopuro P, Khoo SK, Patocs A, Martin C, Bridgeman S, Heinz J, Pilarski R, Lehtonen R, Prior TW, Frebourg T, Teh BT, Marchuk DA, Aaltonen LA, Eng C. Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis. JAMA. 2005;294:2465–73. [PubMed: 16287957]
  • Taylor H, Yerlioglu D, Phen C, Ballauff A, Nedelkopoulou N, Spier I, Loverdos I, Busoni VB, Heise J, Dale P, de Meij T, Sweet K, Cohen MC, Fox VL, Mas E, Aretz S, Eng C, Buderus S, Thomson M, Rojas I, Uhlig HH. mTOR inhibitors reduce enteropathy, intestinal bleeding and colectomy rate in patients with juvenile polyposis of infancy with PTEN-BMPR1A deletion. Hum Mol Genet. 2021;30:1273–82. [PMC free article: PMC8804886] [PubMed: 33822054]
  • Teekakirikul P, Milewicz DM, Miller DT, Lacro RV, Regalado ES, Rosales AM, Ryan DP, Toler TL, Lin AE. Thoracic aortic disease in two patients with juvenile polyposis syndrome and SMAD4 mutations. Am J Med Genet A. 2013;161A:185–91. [PMC free article: PMC3535513] [PubMed: 23239472]
  • van Hattem WA, Brosens LA, de Leng WW, Morsink FH, Lens S, Carvalho R, Giardiello FM, Offerhaus GJ. Large genomic deletions of SMAD4, BMPR1A and PTEN in juvenile polyposis. Gut. 2008;57:623–7. [PubMed: 18178612]
  • Wain KE, Ellingson MS, McDonald J, Gammon A, Roberts M, Pichurin P, Winship I, Riegert-Johnson DL, Weitzel JN, Lindor NM. Appreciating the broad clinical features of SMAD4 mutation carriers: a multicenter chart review. Genet Med. 2014;16:588–93. [PMC free article: PMC4125531] [PubMed: 24525918]
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