Editor—Although the average age of menarche has decreased over the last century, the mean age of menopause appears to be invariant with time and race and occurs at approximately 50 years. The loss of functional follicles occurring in women under the age of 40 is defined as premature ovarian failure. It occurs in about 1-2% of women,1 in some as early as their teens. Before the onset of premature ovarian failure, most women appear to have a normal menstrual history, age of menarche, and fertility.2 Unexplained premature ovarian failure is clinically recognised as amenorrhoea with low levels of oestrogen and raised levels of luteinising hormone (LH) and follicle stimulating hormone (FSH) occurring before the age of 40.

Premature ovarian failure may have a chromosomal, genetic, enzymatic, iatrogenic, autoimmune, or infectious aetiology. In approximately 5% of women with premature ovarian failure there is a significant family history of early menopause.3 However, in most cases, no known cause has been identified.2 Genetic causes have been suggested, and a range of candidate loci have been identified. These regions are currently under investigation to determine the underlying basis of ovarian failure.

The proband (III.10), a 33 year old woman, presented for fertility care. She is the only woman in a sibship of three and her pedigree is shown in fig 1. Her …