Epilepsy and mental retardation limited to females: an X-linked dominant disorder with male sparing

Several X-linked disorders affect females disproportionately or exclusively. These including focal dermal hypoplasia¹,², oral-facial-digital syndrome type I (ref. 3) and epilepsy with bilateral periventricular heterotopias⁴. X-linked dominant inheritance with male lethality is probably responsible for sex-limited expression of these disorders, as affected women have frequent spontaneous abortions and the sex ratio of their live offspring is often skewed⁵. The same inheritance pattern has been proposed for Rett syndrome⁶, Aicardi syndrome⁷ and microphthalmia with linear skin defects⁸, but in these sporadic conditions, evidence of male lethality is lacking. We investigated an unusual family with epilepsy and mental retardation limited to females (EFMR, 121250 in ref. 9); this disorder is transmitted both by females and by completely unaffected carrier males. Assignment of the EFMR disease locus (EFMR) to the X chromosome indicates that selective involvement of females in X-linked disease may in some instances result from male sparing rather than male lethality.

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