OBJECTIVES: I. Investigate phenotype and genotype correlations in patients with
Smith-Magenis syndrome (SMS) associated with del(17p11.2).
II. Clinically evaluate SMS patients with unusual deletions or duplication of proximal 17p.
III. Clinically evaluate patients with Williams syndrome with molecular characterization of
IV. Perform clinical studies of Prader-Willi, Angelman, DiGeorge, and Shprintzen syndrome
patients with unique molecular findings in 15q11q13 or 22q11.2.
V. Perform genotype and phenotype correlations in Prader-Willi patients, particularly those
with loss of expression of only some of the imprinted transcripts in 15q11-q13.
VI. Evaluate putative Angelman syndrome patients who do not have classic large deletion,
uniparental disomy, or imprinting mutations, and perform molecular studies of the Angelman
gene, UBE3A, and identify mutations of this gene.
VII. Investigate phenotype and genotype correlations in patients with terminal deletions of
PROTOCOL OUTLINE: Patients undergo clinical, cytogenetic, and molecular studies. These
include radiographic, neurologic, developmental, and 24 hour sleep studies, ophthalmologic,
otolaryngologic, speech and language, and audiologic exams, echocardiogram, and renal
Smith-Magenis patients are also evaluated with the following: urine melatonin levels during
day and night hours; anthropometrics; sleep and behavioral history; and renal, immunologic,
and cholesterol studies. A clinical and phenotypic map is constructed.
When appropriate, parental chromosome analysis is performed.
PROTOCOL ENTRY CRITERIA:
--Disease Characteristics-- Contiguous gene deletion syndrome, e.g.: Smith-Magenis
syndrome Williams syndrome DiGeorge syndrome Shprintzen syndrome (velo-cardio-facial
syndrome) Prader-Willi syndrome Angelman syndrome Deletion of chromosome 1p Patient age: