NCT00001403

Study of Proteus Syndrome and Related Congenital Disorders

The Phenotype and Etiology of Proteus Syndrome

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 1,500 (estimated)
• Sponsor: National Human Genome Research Institute (NHGRI) · NIH
• Sex: All
• Age: 1 Month – 99 Years
• Healthy volunteers: Not accepted

Summary

This study will examine rare congenital disorders that involve malformations and abnormal growth. It will focus on patients with Proteus syndrome, whose physical features are characterized by overgrowth, benign tumors of fatty tissue or blood vessels, asymmetric arms or legs, and large feet with very thick soles. The study will explore the genetic and biochemical cause and course of the disease, the changes in symptoms over time, and the effects of the disease on patients. Patients with Proteus syndrome may be eligible for this study. Study candidates will have a medical history and physical examination, including X-rays and possibly other imaging tests, such as computerized tomography (CT), magnetic resonance imaging (MRI) and ultrasound. Other tests and examinations may be done if needed. Those enrolled in the study may be interviewed or complete questionnaires, or both, about how their disease affects them. Patients will provide a small blood sample for research....

Detailed description

The purpose of this project is to specifically delineate the phenotype and natural history and genetic etiology of Proteus syndrome (PS) and other overgrowth disorders hypothesized to be in the PI3K/AKT pathway. As we have determined the molecular cause of PS and the related disorder of fibroadipose overgrowth, our main objectives moving forward include genotype-phenotype correlations, identifying quantifiable phenotypic characteristics in patients and measuring changes in these characteristics over time, developing potential biomarkers for future therapeutic research, and using our new molecular insights to expand our understanding of both PS and related overgrowth disorders. The natural history and specific phenotypic characteristics of patients with PS and selected other overgrowth disorders will be determined by clinical assessment and longitudinal follow-up of patients, which includes patients who have been exposed to therapeutic agents, such as an AKT inhibitor. Subjects will be screened for eligibility using published diagnostic criteria for PS; screening for AKT1 and other pathway gene variants may be used in patients with overlapping phenotypes. The discovery of the AKT1 activating variant in patients with this disease provides an attractive target for directed treatment for this devastating disorder. This protocol aims to aid in identifying individuals with molecularly-confirmed AKT1 variants who may be candidates for pharmacologic interventional studies. We also propose to expand our clinical ascertainment to determine the full range of PS/AKT1 activating variant phenotypes and to study other overlapping conditions. The etiology of these disorders will be studied using candidate gene analysis (primarily based on the PI3K/AKT pathway) and possibly exome and whole genome sequencing, performed as part of protocol 10-HG-0065.

Conditions

• Proteus Syndrome
• PIK3CA Related Overgrowth Spectrum

Timeline

• Start date: 1994-04-27
• First posted: 1999-11-04
• Last updated: 2026-04-14

Locations

1 site across 1 country: United States