Prader-Willi syndrome: clinical and molecular cytogenetic investigations.

Prader-Willi syndrome is characterized by hypotonia and feeding difficulties in the neonatal period, with the childhood development of hyperphagia leading to obesity, developmental delay, hypogonadism, short stature and small hands and feet. Correct diagnosis of Prader-Willi syndrome is important because of its clinical implications and the need for family genetic counseling. In order to determine the most efficient method of diagnosing the condition, we evaluated 37 patients with a putative diagnosis of Prader-Willi syndrome by both clinical and molecular cytogenetic analyses. Clinical evaluation showed that 25 patients fulfilled the diagnostic criteria for Prader-Willi syndrome. A deletion of the region 15q11.2-13 was cytogenetically identified in 20 patients using a high-resolution technique. Four additional cases were detected by fluorescence in situ hybridization (FISH) with the cosmid probes for D15S11, r-aminobutyric acid receptor beta 3 (GABRB3), small nuclear ribonucleoprotein-associated peptide N (SNRPN) or D15S10 (Prader-Willi/ Angelman syndrome region probes). The deletion of SNRPN was documented in 24 Prader-Willi syndrome patients. Only one additional patient with typical Prader-Willi syndrome features did not have any deletion over 15q11-13 at either the cytogenetic or molecular level. FISH provides a more reliable method than high-resolution chromosome analysis for the diagnosis of Prader-Willi syndrome. Associated conditions such as hypopigmentation, small-joint laxity, arachnodactyly, seizure disorder, optic atrophy, congenital heart disease, Perthes' disease, hirsutism, astigmatism/amblyopia, microcephaly and neuropsychiatric disturbances dictate the effects of a contiguous gene syndrome. Morbidity is high among patients with obesity and associated conditions. Appropriate genetic counseling should be given to the parents and dietary management should be helpful for patients with Prader-Willi syndrome.