Ovarian dysgenesis with a normal 46,XX karyotype is defined by reduced or altered ovaries, a female phenotype, and normal stature with no turnerian malformations. Diagnosis is suggested by primitive hypergonadotropic hypogonadism with a normal 46,XX karyotype. In some cases a genetic origin has been identified. For the other cases, unidentified autosomal and gonosomal genes may be involved in the development and maintenance of ovarian function:
Syndromic Hypergonadotropic Hypogonadism
Perrault syndrome is an autosomal recessive ovarian dysgenesis with possible deafness. The defective gene has not yet been identified.
Type I BPEIS (blepharophimosis psosis epicanthus inversus syndrome) can be associated with delayed puberty or, more frequently, with premature ovarian failure. The mode of inheritance is autosomal dominant and transmitted by males because women are always infertile with ovarian streaks. The gene has been identified on chromosome 3.
Congenital galactosemia is associated with primary ovarian failure diagnosed mostly at an early age. Metabolic toxicity already impairs follicular cells during fetal life.
Inactivating Mutation of the FSH or LH Receptor
An inactivating mutation of the FSH receptor was first described in Finland and is associated with either primary amenorrhea or premature ovarian failure. The ovaries have normal size and biopsies show the presence of multiple pre-antral follicles. This corresponds to the ovarian resistance to gonadotropins, or Savage syndrome. The gene encoding for the FSH receptor is located on chromosome 2 and the mode of inheritance is autosomal recessive.
Although two observations were recently described in France, a study from the USA failed to find any mutated FSH-R gene among 35 cases of premature ovarian failure.
A few observations have been reported with an inactivating mutation of the gene encoding for the LH receptor in homozygotic XX women with primary amenorrhea, developed sex characteristics, and high LH level but normal FSH level with normal ovarian follicles but without any luteal corpus.
Revision date: June 20, 2011
Last revised: by Jorge P. Ribeiro, MD