JP-HHT phenotype in Danish patients with SMAD4 mutations.
A M Jelsig1,2, P M Tørring1, A D Kjeldsen3
1Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
Clinical Genetics
|November 18, 2015
Summary
Germline SMAD4 mutations cause JP-HHT syndrome, combining juvenile polyposis syndrome and hereditary hemorrhagic telangiectasia. Patients often exhibit both conditions, with higher risks of pulmonary arteriovenous malformations and gastric polyps.
Area of Science:
- Genetics
- Medical Genetics
- Syndromology
Background:
- Germline mutations in SMAD4 gene are associated with Juvenile Polyposis Syndrome (JPS) and Hereditary Hemorrhagic Telangiectasia (HHT).
- The combined phenotype, known as JP-HHT syndrome, presents a complex clinical picture that is not fully understood.
- Understanding the complete spectrum of SMAD4-related disorders is crucial for accurate diagnosis and management.
Purpose of the Study:
- To describe the clinical characteristics of patients with SMAD4 mutations.
- To investigate the co-occurrence and frequency of symptoms related to JPS and HHT in SMAD4 mutation carriers.
- To highlight the potential for aortopathy in patients with SMAD4 mutations.
Main Methods:
- Retrospective, register-based study utilizing the Danish HHT-registry and genetic databases.
- Identification of SMAD4 mutation carriers through registries and genetic laboratories.
- Review of medical records to document symptoms of HHT, JPS, aortopathy, and family history.
Main Results:
- Fourteen patients with SMAD4 mutations were identified.
- All patients underwent polyp removal; 11 met diagnostic criteria for JPS.
- Seven of eight screened patients fulfilled criteria for HHT, and one patient had aortic root dilation.
Conclusions:
- SMAD4 mutation carriers frequently present with symptoms of both HHT and JPS.
- The frequency of pulmonary arteriovenous malformations and gastric polyps may be higher in SMAD4-related JP-HHT syndrome compared to non-SMAD4 related HHT or JPS.
- There is a need for increased screening for aortopathy in patients with SMAD4 mutations.
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