Genetic epidemiology of Menkes disease

Copper incorporation studies were performed on individuals from 58 pedigrees, comprising 140 sibships. As previously reported, there is considerable overlap between heterozygotes and normal homozygotes. Segregation analysis supports recessive inheritance of disease, with residual heritability for 64Cu uptake in cultured cells. The population frequency of sporadic cases is compatible with the 1/3 expected for an X-linked lethal with equal mutation rates in egg and sperm, which implies a mutation rate of 6.7 X 10(-6)/gamete/generation. The parameters estimated here are likely to provide the best basis for genetic counseling until more reliable carrier tests are performed on a systematic sample from a large, defined population.