Prader-Willi Syndrome (Prader-Labhart-Willi syndrome)

A very rare (prevalence 1/25,000) dominant defect involving poor muscle tension, hypogonadism, (hyperphagia [over-eating]) obesity, short stature, small hands and feet, mental retardation, compulsive behavior that sets in by the teens, caused by methylation of the paternal chromosome and by disomy for maternal chromosome 15 (see Fig. P121). The recurrence risk in affected families is about 1/1000. This and cytological evidence indicate that the condition is caused in about 60% of the cases by a chromosomal breakage in the so-called imprinting center (IC) in the long arm of human chromosome 15q11.2-q12. The same deletion (4–5 Mbp or sometimes shorter), when transmitted through the mother, results in the Angelman syndrome. At the breakpoints, the HERC2 gene (encoding a very large protein) may be repeated. The repeats may then recombine and generate the deletions. See two chromosomes shown in Figure P122, with different number of repeats, as detected by FISH. In some cases, there is no...