Endocrine Abstracts

Introduction: Nijmegen breakage syndrome(NBS) represents a rare autosomal recesive disorder, characterized by severe chromosomal instability. It is caused by mutations in the NBN gene, which product, nibrin, belongs to the hMre11/hRad50 protein complex, critical for processing DNA double-strand breaks during mitotic and meiotic recombination. The hallmarks of NBS are growth retardation, microcephaly, premature ovarian failure(POI) in females, immunodeficiency and predisposition for malignancy.

Case report: A 9-year-old girl presented in the Department of Endocrinology Iasi with a history of two vaginal bleeding episodes and recurrent respiratory infections. Her clinical features were short stature (G=23 kg, T=127 cm, -1.78 SD->Pascanu), craniofacial dysmorphia with microcephaly, up-slanting palpebral fissures, long nose, sloping forehead, micrognathia and Sutton’s nevi, no clinical signs for secondary sexual characteristics development, borderline intellectual ability. Biological tests were normal, but the hormonal assessment showed hypergonadotrophic hypogonadism (increased FSH=69,9 mUI/ml and LH=13,3 mIU/ml and low estradiol< 20 pg/ml). The pelvic ultrasonographic (US) examination reveals small uterus and ovarian sizes, regardless of age, without ovarian follicles. The karyotype and MLPA for SHOX gene deletion were normal. The two episodes of vaginal bleeding were interpreted in a mild pelvic traumatic injury context (falling from the bicycle). Six months later, she developed extensive vitiligo lesions on her lower body. The suspicion for Nijmegen Breakage Syndrome was confirmed by the Sanger sequencing, which identified the mutation of the Nibrin gene (NBN) in exon 6: c.657_661delACAAA, in a homozygous state. When she was 12 years old, we started the treatment for pubertal induction with low doses of transdermic estradiol.

Discussions: NBS is caused by mutations in the NBN gene, which product, nibrin, belongs to the hMre11/hRad50 protein complex, critical for processing DNA double-strand breaks during mitotic and meiotic recombination. The hallmarks of NBS are growth retardation, microcephaly, premature ovarian insufficiency (POI) in females, immunodeficiency and predisposition for malignancy. Our case is an unusual presentation for the NBS – suspicion of precocious puberty with vaginal bleeding. In the literature, NBS is associated with premature ovarian failure. The pathomechanism of hypoplastic ovaries or streaks gonadal is explained by genome instability.