Ovarian Dysgenesis 8
A number sign (#) is used with this entry because of evidence that ovarian dysgenesis-8 (ODG8) is caused by heterozygous mutation in the ESR2 gene (601663) on chromosome 14q23. One such patient has been reported.
DescriptionOvarian dysgenesis-8 (ODG8) is characterized by complete lack of estrogen action, resulting in absent breast development, primary amenorrhea, and osteoporosis (Lang-Muritano et al., 2018).
For a discussion of genetic heterogeneity of ovarian dysgenesis, see ODG1 (233300).
Clinical FeaturesLang-Muritano et al. (2018) studied a 16.5-year-old 46,XX East African orphan who presented with absent breast development, fully developed pubic hair, and primary amenorrhea. Examination revealed a eunuchoid habitus, hypoplastic labia majora, and nonestrogenized infantile vulva, with otherwise normal anatomy. Abdominal ultrasound showed a small infantile uterus; ovaries were not detected. She also had severe osteoporosis on dual-energy x-ray absorptiometry. Laboratory examination showed low serum E2 estradiol, elevated luteinizing hormone (LH; see 152780) and follicle-stimulating hormone (FSH; see 136530) levels, and very low anti-Mullerian hormone (AMH; 600957). Estrogen therapy resulted in breast development, and menarche occurred after the first month of cyclic hormone replacement. Ultrasonography after estrogen replacement showed stimulated endometrium and increased uterus volume, and ovaries were identifiable as streaks without follicles. Bone density improved but was still abnormal after 2 years of treatment with estrogen, calcium, and vitamin D3.
Molecular GeneticsIn a 16.5-year-old 46,XX East African orphan with ovarian dysgenesis, Lang-Muritano et al. (2018) performed whole-exome sequencing and identified heterozygosity for a missense mutation in the ERS2 gene (K314R; 601663.0001) that was not found in 300 controls or in the ExAC database. Examination of the exome data did not reveal any pathogenic variants in known premature ovarian failure- or other ESR pathway-associated genes.