Female sex preponderance for idiopathic familial premature ovarian failuresuggests an X chromosome defect

Premature ovarian failure (POF) is defined as ovarian failure occurring bef ore the age of 40 years, A genetic aetiology is suggested by the occurrence of families with two or more affected females. We have characterised the p attern of inheritance of 41 cases of familial POF and compared them to publ ished pedigrees, In eleven families a clear genetic association of POF coul d be identified. In the remaining 30 families the mechanism of inheritance was obscure. We found a female sex preponderance in the siblings of 30 fami lies with idiopathic POF and in previously published series of idiopathic f amilial POF, In contrast, other known causes of POF, such as blepharophimos is ptosis epicanthus and inversus and autosomal recessive gonadal dysgenesi s, had no altered sex ratio. One of our series of 30 pedigrees demonstrated transmission of POF susceptibility through fathers, which vee believe is t he first to be described in the literature. We present a group of five cons anguineous families where we assume the mode of inheritance is autosomal re cessive and where there was no female sex preponderance. Female ses prepond erance for idiopathic familial POF suggests an X chromosome defect is inher ited as a major cause of ovarian failure.