High Prevalence of Primary Ovarian Insufficiency in Girls and Young Women with Nijmegen Breakage Syndrome: Evidence from a Longitudinal Study

Context: Nijmegen breakage syndrome (NBS) is a severe chromosomal instability disorder characterized by microcephaly, growth retardation, immune deficiency, and predisposition for malignancy. It is caused by hypomorphic mutations in the NBN gene, which product belongs to the protein complex critical for processing DNA double-strand breaks during mitotic and meiotic recombination. Data on gonadal function in patients with NBS are limited. Objective: Growth and sexual development, along with hormonal assays, were evaluated in girls and young women with NBS homozygous for c.657_661del5 mutation. Study Design and Patients: The group comprised 37 girls and young women with NBS (ages, 0.17–24.25 yr), followed between 1993 and 2008. Patients were divided into three age groups: 1) 1–3 yr; 2) 4–9 yr; and 3) 10 yr and older. Growth, puberty, concentrations of gonadotropins and 17-β-estradiol, bone age, and pelvic ultrasound were assessed. Results: None of the patients presented a typical growth spurt; the adult hei...