Female sex preponderance for idiopathic familial premature ovarian failure suggests an X chromosome defect: opinion

Abstract

Premature ovarian failure (POF) is defined as ovarian failure occurring before 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 pattern of inheritance of 41 cases of familial POF and compared them to published pedigrees. In eleven families a clear genetic association of POF could be identified. In the remaining 30 families the mechanism of inheritance was obscure. We found a female sex preponderance in the siblings of 30 families with idiopathic POF and in previously published series of idiopathic familial POF. In contrast, other known causes of POF, such as blepharophimosis ptosis epicanthus and inversus and autosomal recessive gonadal dysgenesis, had no altered sex ratio. One of our series of 30 pedigrees demonstrated transmission of POF susceptibility through fathers, which we believe is the first to be described in the literature. We present a group of five consanguineous families where we assume the mode of inheritance is autosomal recessive and where there was no female sex preponderance. Female sex preponderance for idiopathic familial POF suggests an X chromosome defect is inherited as a major cause of ovarian failure.