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 and their parents may be eligible for this study. Parents will be studied, when possible, for comparison of molecular findings. 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 will have will be interviewed or complete questionnaires, or both, about how their disease affects them. (Parents will be asked about their feelings about having a child with a rare disorder.) Patients will provide a small blood sample for research and may be asked to undergo biopsies from a normal area of skin and from a tumor.

Condition
Growth Disorder Mental Retardation Multiple Abnormalies

Further Study Details: 

Expected Total Enrollment:  1500

The purpose of this project is to determine the natural history and etiology of Proteus syndrome. The natural history and the phenotypic range will be determined by clinical assessment and longitudinal follow-up of a cohort of patients. Subjects will be screened for eligibility using published diagnostic criteria for Proteus syndrome. The determination of the molecular etiology of this disorder will be difficult. It is extremely rare, affected patients have a shortened lifespan, and the disorder is sporadic. Thus the typical approach of positional cloning is not useful. The etiology of this disorder will be studied using various comparative molecular biology techniques including cDNA arrays, genomic arrrays, subtractive techniques, testing of candidate genes, and other appropriate techniques. We will also test for dysregulation of growth controlling hormones and binding proteins in vivo.

Note is made that although this protocol is currently structured to recruit only subjects with Proteus syndrome, it was previously used for a more general group of sporadic birth defect syndromes. The original goals for that group have been accomplished, which was the determination of the frequency of submicroscopic chromosomal rearrangements and uniparental disomy. That group of patients (and unaffected parents) is no longer being recruited but the specimens are retained. These specimens will be tested for appropriate candidate genes if, and when, that opportunity should arise.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
For Proteus Patients
All affected sugjects should have the following general criteria: mosaic distribution of lesions, progressive course, and sporadic occurrence.
In addition, they should have either 1 from A, 2 from B or 3 from C.
A. Connective tissue nevus.
B. Epidermal nevus, Disproportionate overgrowth, specific tumors before the age of 30 yrs (bilat. ovarian cystadenomas or monomorphic parotid adenoma).
C. Dysregulated adipose tissue, Vascular malformations, Facial phenotype.
The Proteus send-in subjects must meet the same eligibility standards as those who come to the clinical center and this will be determined by the review of the materials.

Maryland
      National Human Genome Research Institute (NHGRI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  940132; 94-HG-0132
Record last reviewed:  April 15, 2004
Last Updated:  November 23, 2004
Record first received:  November 3, 1999
ClinicalTrials.gov Identifier:  NCT00001403
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08