A case of premature ovarian insufficiency in Nijmegen breakage syndrome patient and review of literature. From gene mutation to clinical management

Abstract

Background: Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder leading to chromosomal instability and an array of symptoms, including characteristic facial features (bird-like face), predisposition to malignancies, as well as hypergonadotropic hypogonadism. This case report discusses the diagnostic process and management of a 23-year-old Polish female patient who was admitted to hospital with symptoms of secondary amenorrhea and clinical features corresponding to NBS.

Methods: Clinical examination, per-rectal ultrasound, laboratory diagnostics (including serum concentrations of FSH, LH, estradiol, testosterone, and TSH), as well as SSCP analysis and classic karyotyping were performed.

Results: During hormonal evaluation elevated serum concentration of FSH and LH and decreased serum concentration of estradiol were measured. The genetic testing revealed translocation 7;14 (t(7;14)) and inversion 7 in 22% of examined cells which confirmed the initial hypothesis of NBS. The diagnosis was finally verified by identifying a Slavic founder mutation, c.657_661del5, on both allels of the NBN gene. Furthermore, hormonal serum evaluation conducted after four weeks allowed the patient to be diagnosed with premature ovarian insufficiency (POI) suspected earlier on the grounds of preliminary examinations (ultrasound imaging and laboratory tests).

Conclusions: Chromosomal instability resulting from a mutation present in Nijmegen breakage syndrome patients might be a causative factor of premature ovarian insufficiency. Therefore, females diagnosed with NBS should undergo additional diagnostic procedures in order to determine further management and treatment.

摘要

背景：尼梅亨断裂综合征（NBS）是一种常染色体隐性遗传病, 可导致染色体不稳定和一系列症状, 包括特征性面部特征（鸟样脸）、易患恶性肿瘤以及性腺功能亢进或减退。本病例报告探讨一名23岁波兰女性患者因继发性闭经症状及与NBS相对应的临床特征而入院治疗的过程与处理。

方法：临床检查、直肠超声检查、实验室诊断（包括血清FSH、LH、雌二醇、睾酮、TSH浓度）、SSCP分析及经典核型分析。

结果：在激素评价期间, 测定血清FSH、LH浓度升高和雌二醇浓度降低。基因检测显示, 22%的受检细胞发生易位（t（7;14））和倒置, 证实了NBS的最初假设。最后, 通过识别斯拉夫创始人突变, 即NBN基因的两个等位基因上的657 - 661del5得以确诊NBC。此外, 在4周后进行的血清激素评估使患者能够在早期的初步检查（超声成像和实验室检测）基础上确诊为卵巢早衰(POI)。

结论：尼梅亨断裂综合征患者染色体突变引起的染色体不稳定可能是导致卵巢功能不全的原因之一。因此, 诊断为NBS的女性应进行额外的诊断程序, 以便进行进一步的管理和治疗。

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• Premature ovarian insufficiency
• Nijmegen Breakage Syndrome
• NBN gene
• nibrin

Disclosure statement

No potential conflict of interest was reported by the authors.