EPILEPSY AND MENTAL-RETARDATION LIMITED TO FEMALES - AN X-LINKED DOMINANT DISORDER WITH MALE SPARING

Several X-linked disorders affect females disproportionately or exclus ively. These including focal dermal hypoplasia(1,2), oral-facial-digit al syndrome type I (ref. 3) and epilepsy with bilateral periventricula r heterotopias(4). X-linked dominant inheritance with male lethality i s probably responsible for sex-limited expression of these disorders, as affected women have frequent spontaneous abortions and the sex rati o of their live offspring is often skewed(5). The same inheritance pat tern has been proposed for Rett syndrome(6), Aicardi syndrome(7) and m icrophthalmia with linear skin defects(8), but in these sporadic condi tions, evidence of male lethality is lacking. We investigated an unusu al family with epilepsy and mental retardation limited to females (EFM R, #121250 in ref. 9); this disorder is transmitted both by females an d by completely unaffected carrier males. Assignment of the EFMR disea se locus (EFMR) to the X chromosome indicates that selective involveme nt of females in X-linked disease may in some instances result from ma le sparing rather than male lethality.