The evaluation of ovarian function in normosmic idiopathic hypogonadotropic hypogonadism with a fibroblast growth factor receptor 1 mutation: a case report

Abstract

Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) is a rare disorder with pubertal delay, normal sense of smell. nIHH with a fibroblast growth factor receptor 1 mutation is much more common in adult males but is rarely reported in females. In addition, the assessment and monitoring of ovarian function in nIHH females has often been ignored. We report a 24-year-old nIHH female with the complaint of primary amenorrhea and delayed secondary sexual traits development. Whole-Exome Sequencing analysis revealed a novel mutation in the third exon of fibroblast growth factor receptor 1 gene (c.289 G > A), which resulted in the replacement of glycine acid with serine. Then the patient was recommended to start with the hormone therapy (HT). After several months of estrogen combined with progesterone replacement, the patient had regular menstruation. The breast development and genital development gradually became Tanner stage 5. Anti-Müllerian hormones (AMHs) were also evaluated and the serum AMH level keeps fluctuating within the normal reference range. We highlight the great variability of fibroblast growth factor receptor 1 mutation phenotypes and the evaluation of ovarian reserve in nIHH, and the hormone replacement therapy is necessary to improve secondary sexual development for patients with nIHH.

嗅觉正常的特发性低促性腺激素性性功能减退症并伴成纤维细胞生长因子受体1突变的卵巢功能评估:1例病例报告 摘要

嗅觉正常的特发性低促性腺激素性性功能减退症(nIHH)是一种罕见的疾病与青春期发育延迟相关并伴有嗅觉正常。伴有成纤维细胞生长因子受体1突变的nIHH在成年男性中更为常见, 但在女性中很少报道。并且nIHH女性卵巢功能的评估和监测经常被忽视。我们报道了一位24岁的nIHH女性主诉因原发性闭经和第二性发育延迟等特征就诊。全外显子测序分析显示成纤维细胞生长因子受体1基因的第三外显子有一个新的突变(c.289G > A), 导致甘氨酸被丝氨酸取代。建议患者开始激素治疗(HT)。在雌激素联合孕激素替代治疗几个月后, 患者月经正常。乳房发育和生殖器官发育逐渐进入Tanner分期 5期。血清抗苗勒管激素(AMH)水平在正常区间波动。我们强调注重nIHH中成纤维细胞生长因子受体1突变表型患者的卵巢储备功能的评估, 以及激素替代治疗对于改善nIHH患者的继发性发育迟缓是必要的。

Keywords:

• Normosmic idiopathic hypogonadotropic hypogonadism
• fibroblast growth factor receptor 1
• hormone therapy
• anti-Müllerian hormone

Ethics approval and consent to participate

The study was approved by the Ethics Committees of the International Peace Maternity and Child Health Hospital, and the patient provided written informed consent.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Author contributions

LLW drafted the manuscript and performed the literature review. DML confirmed the diagnosis, and revised the manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

All data related to this case report are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant number 81971334] and the Shanghai Municipal Council for Science and Technology [grant number 18410721200], [grant number 20JC1412100].