Juvenile polyposis syndrome (JPS, OMIM #174900) is a genetic disease caused by heterozygous mutations in the BMPR1A or SMAD4 gene. It is characterized by the occurrence of juvenile hamartomatous gastrointestinal polyps and a predisposition to gastrointestinal tumors. In addition, mutations in the SMAD4 gene are also associated with hereditary hemorrhagic telangiectasia (HHT).

Key Data

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Genes BMPR1A
Gene products Bone morphogenetic protein receptor type 1A (BMPR1A)
Mothers against decapentaplegic homolog 4 (SMAD4)
Function Tumor suppressors, associated with the TGF-β signaling pathway
Heredity Autosomal dominant, around 67% de novo mutations
Prevalence The incidence is between 1:16.000 and 1:100.000.
Genotype-phenotype correlation SMAD4 mutations are associated with hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease).

SMAD4 mutations go hand-in-hand with a greater risk of polyps in the upper GI tract, whereby this phenotype presumably has a more aggressive progression and is associated with significant polyposis and a greater risk of gastric carcinomas.

Patients with an SMAD4 or BMPR1A mutation are more likely to have > 10 polyps in the lower GI tract and a positive family history of gastrointestinal malignancies than patients without evidence of a mutation.

Penetrance 97% of patients develop colonic polyps, 68% gastric polyps, and 76% exhibit signs of HHT.
The cumulative lifetime risk of a colorectal carcinoma is 39%. The risk of a gastric carcinoma is 21% in patients with gastric polyps.
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Clinical Diagnostics

Juvenile polyposis syndrome is suspected when the following findings apply:

  • Anemia, rectal bleeding, prolapsed rectal polyps

  • > 1 juvenile polyp

  • ≥ 1 juvenile polyp and a concomitant JPS family history

Clinical Diagnostic Criteria

The diagnosis of “juvenile polyposis syndrome” is confirmed by the presence of one of the following findings:

  • > 5 juvenile polyps in the colon or rectum

  • Multiple juvenile polyps in the upper and lower GI tract

  • Any number of juvenile polyps and a concomitant juvenile polyposis family history

  • The presence of a heterozygous SMAD4 or BMPR1A mutation

Genetic Diagnostics

The diagnosis of “juvenile polyposis syndrome” is confirmed by detection of a heterozygous germline mutation in the SMAD4 or BMPR1A gene through sequence analysis or deletion/duplication analysis. The use of panel examinations consisting of multiple genes as well as exome or genome sequencing may be helpful as well.

Differential Diagnoses

  • PTEN hamartoma tumor syndrome, also Cowden syndrome

  • Nevoid basal cell carcinoma syndrome, also Gorlin syndrome

  • Peutz-Jeghers syndrome

  • Hereditary mixed polyposis syndrome

  • Familial adenomatous polyposis (FAP)

  • MUTYH-associated polyposis

  • Hereditary non-polyposis colorectal carcinoma, also Lynch syndrome

  • Hereditary hemorrhagic telangiectasia (HHT) without a SMAD4 mutation

Clinical Presentation


Hamartomatous polyps occur in both the upper and lower gastrointestinal tract and exhibit a wide variety of shapes and sizes: Both sessile and stalked polyps occur, and their number ranges between only a few to over 100 polyps. Juvenile polyps (whereby “juvenile” refers to the histology and not the age of the patient) may develop from infancy to adulthood. Most JPS patients exhibit polyps at the age of 20. Hemorrhaging, and resulting anemia, is a potential complication.

While most juvenile polyps are benign, malignant transformations may also occur. The incidence of colorectal carcinomas is 17-22% at 35 years of age, increasing to 68% at the age of 60. The average age at colon carcinoma diagnosis is 42. The incidence of gastric carcinomas is 21% in patients with gastric polyps.

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

JPS/HHT syndrome can occur in patients with a SMAD4 mutation and exhibit variable manifestations of juvenile polyposis and HHT. The latter may be epistaxis, telangiectasia, arteriovenous malformations (AVS), or drumstick fingers. Clinical symptoms usually appear during early childhood, with pulmonary AVM and epistaxis almost always occurring. Complications of JPS/HHT syndrome may include anemia, migraines, and headaches.

In addition, a SMAD4 mutation may lead to thoracic aortic diseases such as aortic root dilation, aneurysms, and mitral valve dysfunctions.

Therapeutic Considerations

An endoscopic polypectomy should be performed as early as possible and may reduce the risk of malignant transformation, hemorrhaging, or intestinal obstructions. When there are a large number of polyps or severe symptoms, a total or subtotal colectomy may be helpful.

JPS/HHT syndrome should be treated like other forms of hereditary hemorrhagic telangiectasia.

Surveillance Recommendations

Surveillance Recommendations

Patients with SMAD4 or BMPR1A Mutations or Clinically Diagnosed JPS:

  • An annual medical history, clinical examination, and complete blood count, especially with regard to rectal bleeding, anemia, abdominal pain, constipation, diarrhea, or changes in stool shape, size, or color

  • A colonoscopy and esophagogastroduodenoscopy should be performed from the age of 15 or from the time symptoms initially appear.

    • With negative findings: Repeat every 3 years.
    • If there are only a few polyps: Polypectomy (polyps ≥ 5 mm). Screening should be continued every year until no additional polyps are detected, after which the interval can be extended to every 3 years.
    • If there are many polyps: Total/subtotal gastrectomy and/or colectomy as needed. Screening should be continued every year until no additional polyps are detected, after which the interval can be extended to every 3 years.

Additionally for Patients with a SMAD4 Mutation:

  • An annual medical history and clinical examination, especially with regard to epistaxis, other hemorrhaging, shortness of breath, headaches, or neurological symptoms

  • Regular determination of hematocrit, hemoglobin, and ferritin levels and treatment of any iron deficiency anemia

  • MRI of the skull depicting the vessels in the first months of life, repeated after puberty

  • Transcutaneous oxygen measurement every 1-2 years starting in early childhood, with CT of the thorax or a transthoracic echocardiogram if there are any anomalies

  • Regular reevaluation of pulmonary AVM after puberty, before a planned pregnancy, after a pregnancy, and every 5 years with

    • a contrast echocardiogram
    • CT of the thorax with contrast agent if a right-to-left shunt was diagnosed on the contrast echocardiogram performed beforehand

Additional Information

Open Clinical Trials / Registries

Support Groups

Unfortunately, we are as yet unaware of any existing support groups for patients with juvenile polyposis syndrome. We will add new information as it becomes available.