Cher Wen Qi, Chan Daniel
Department of Paediatric Medicine, KK Women's and Children's Hospital, Singapore 229899, Singapore.
Paediatric Academic Clinical Programme, Singapore Health Services, Singapore 229899, Singapore.
JCEM Case Rep. 2025 Jun 10;3(7):luaf126. doi: 10.1210/jcemcr/luaf126. eCollection 2025 Jul.
A 15-year-old female individual presented with primary amenorrhea and absence of pubertal signs. Her hormonal profile revealed isolated hypogonadotropic hypogonadism (IHH) with low levels of luteinizing hormone (LH), estradiol, and follicle-stimulating hormone (FSH), with a confirmatory luteinizing hormone-releasing hormone (LHRH) stimulation test. She has a background of global developmental delay and bilateral hearing loss, with computed tomography (CT) findings of an absent right incus lenticular process and a dilated right vestibule. Genetic testing revealed a heterozygous pathogenic variant c.152G>A (p.Trp51*) in the gene. (sex-determining region Y-box 2) is a transcription factor critical for early pituitary and hypothalamic development. However, the phenotype associated with pathogenic variants remains incompletely defined due to its rarity and wide phenotypic variability. Our case uniquely highlights temporal bone anomalies and a comprehensive pituitary function workup, which may contribute to a clearer understanding of -related phenotypic presentations. This case underscores the need to consider pathogenic variants in the genetic evaluation of IHH, even in the absence of ocular abnormalities.
一名15岁女性出现原发性闭经且无青春期体征。她的激素检查显示为孤立性低促性腺激素性性腺功能减退（IHH），黄体生成素（LH）、雌二醇和卵泡刺激素（FSH）水平低，黄体生成素释放激素（LHRH）刺激试验进一步证实。她有全面发育迟缓及双侧听力丧失的病史，计算机断层扫描（CT）发现右侧砧骨豆状突缺如及右侧前庭扩张。基因检测显示该基因存在杂合致病性变异c.152G>A（p.Trp51*）。（性别决定区Y盒2）是一种对早期垂体和下丘脑发育至关重要的转录因子。然而，由于其罕见性和广泛的表型变异性，与该基因致病性变异相关的表型仍未完全明确。我们的病例独特地突出了颞骨异常和全面的垂体功能检查，这可能有助于更清楚地了解与该基因相关的表型表现。该病例强调，即使没有眼部异常，在IHH的基因评估中也需要考虑该基因的致病性变异。
