Hypergonadotropic ovarian failure has many etiologies and varied expressions. Its most common and physiological type occurs during menopause, when ovarian function is gradually put to sleep and compensatory efforts of the female pituitary fail to overcome the estrogen deficiency state. Much earlier in life, at puberty, difficulties may arise from the opposite problem, namely a failure of ovarian awakening, maturation and responsiveness to elevated circulating levels of LH and FSH. Despite intact sex determination and anatomically normal internal and external genitalia, affected teenagers may present with variably developed secondary sex characteristics, primary amenorrhea and poorly developed streak ovaries, a rare and mostly sporadic condition termed ovarian dysgenesis (ODG).
Careful examination of the published literature led Simpson and colleagues (1) in 1971 to suspect that some cases of ovarian dysgenesis in individuals with a normal XX karyotype may be caused by autosomal recessive mutations. Subsequently, a population-based study of ODG revealed