Inheritance in idiopathic premature ovarian failure: analysis of 71 cases

Abstract

Premature ovarian failure is defined as cessation of ovarian function under the age of 40 years and affects approximately 1% of women in the general population. The aetiology of this disorder is still unknown in most cases. Although there have been some reports of familial premature ovarian failure, very little is known about the incidence and inheritance pattern of its idiopathic form. The aims of this study were to investigate the incidence and inheritance pattern of familial premature ovarian failure in a homogeneous group of patients with premature idiopathic menopause and to identify possible clinical differences between patients with the familial and the sporadic form of premature ovarian failure. A total of 71 women were recruited into the study. Clinical assessments and genetic counselling showed that 22 (31%) patients had familial premature ovarian failure, this high incidence strongly suggesting that the disorder is a recognizable heritable entity. There was a statistically significant (P < 0.05) difference in the median age of precocious menopause in patients with sporadic and familial premature ovarian failure (31.0 and 37.5 years of age in the two groups, respectively). Pedigree analysis strongly suggests the existence of a familial pattern of premature ovarian failure with a dominant maternal and/or paternal transmission and incomplete penetrance. In the presence of familial history of premature ovarian failure, reproductive counselling is recommended.

Genetic associations with diminished ovarian reserve: a systematic review of the literature

“…A GWAS database has already begun to emerge for POI cases [10]. POI has proven to be largely familial [21,22]. As we have shown here, evidence supports that pathologic DOR behaves in a similar fashion.…”

“…For example, a study examining 71 chromosomally normal patients characterized as idiopathic POI found 31 % of cases to be familial, exemplifying the large genetic basis of POI [22]. The purpose of this review is to identify the genes that may be associated with pathologic DOR, including those found in humans, as well as candidate genes found in mice, to achieve the goal of ultimately developing a genetic screening panel for pathologic DOR prior to initiating an IVF cycle.…”

Insight into the Genomics of Premature Ovarian Failure

“…Although epidemiological evidence based on mother-daughter pairs supports the heritability of menopausal age [95,96] and some Authors reported cases of familial premature menopause [97,98], very little is known about the inheritance pattern of the idiopathic POF. The overall incidence of familial POF ranges between 4% and 31% depending on the inclusion criteria adopted and the availability of a detailed family history [95,96,98].…”

“…The overall incidence of familial POF ranges between 4% and 31% depending on the inclusion criteria adopted and the availability of a detailed family history [95,96,98]. However, due to rare familial cases with full pedigrees, few genome-wide linkage analyses have been performed so far.…”

“…On one hand, the most accepted theory suggests an either maternal or paternal dominant transmission of POF [98,100]. It is often difficult to distinguish an autosomal dominant pattern of inheritance from an X-linked one since transmitting males with both affected and unaffected daughters, while expected for autosomal dominant inheritance can also occur with X-linkage if penetrance is incomplete.…”