Pan Lili, Li Zhuoguang, Su Zhe, Su Wei, Zheng Rongfei, Chen Weiyan, He Xuezhi, Song Jianming, Li Shoulin, Wen Pengqiang
Department of Endocrinology, Shenzhen Children's Hospital, Shenzhen, China.
Department of Neural Electrophysiology, Shenzhen Children's Hospital, Shenzhen, China.
Front Genet. 2022 Aug 22;13:954288. doi: 10.3389/fgene.2022.954288. eCollection 2022.
Desert hedgehog (DHH), as a member of the Hedgehog (HH) family, is mainly involved in testicular development and peripheral nerve sheath formation. A variant has been identified in patients with 46, XY gonadal dysgenesis (46, XY GD) with or without neuropathy, but few reports mention the involvement of other complications. Here, we report a Chinese female patient who was hospitalized at 14.3 years old due to slow breast development for more than 1 year. She had a female genitalia phenotype and breast development started at 13 years old but progressed slowly. She was not yet menarche on admission, and she had intermittent muscle cramps in her hands and feet. Her karyotype analysis was 46, XY and the gene was positive. Surgical exploration revealed no uterus or ovaries, and the pathology of bilateral gonads was dysplastic testis tissue, which was consistent with partial gonadal dysgenesis (PGD). Genetic analysis identified a homozygous pathogenic variant in exon 3 (c.1027T>C, p. Cys343Arg). During the 6-year follow-up, she received estrogen replacement therapy, resulting in breast development progression without gender dysphoria. However, her peripheral neuropathy became more obvious, and a nerve conduction study (NCS) indicated decreased nerve conduction velocity and action potential. In addition, she also suffered complications such as obesity, insulin resistance, fatty liver, and gastric ulcers. In the present study, we reported a case of 46, XY GD with minifascicular neuropathy caused by a homozygous variant, and we summarized the reported cases worldwide. For the first time in such patients, we showed a comparison of NCS changes with age as well as the presence of multiple complications not previously reported.
沙漠刺猬因子（DHH）作为刺猬因子（HH）家族的一员，主要参与睾丸发育和周围神经鞘形成。在患有或未患有神经病变的46,XY性腺发育不全（46,XY GD）患者中已鉴定出一种变体，但很少有报告提及其他并发症。在此，我们报告一名14.3岁的中国女性患者，因乳房发育迟缓超过1年入院。她具有女性生殖器表型，乳房发育始于13岁，但进展缓慢。入院时仍未初潮，且手脚有间歇性肌肉痉挛。她的核型分析为46,XY，该基因呈阳性。手术探查未发现子宫或卵巢，双侧性腺的病理检查为发育异常的睾丸组织，符合部分性腺发育不全（PGD）。基因分析在第3外显子中鉴定出一个纯合致病变体（c.1027T>C，p.Cys343Arg）。在6年的随访中，她接受了雌激素替代治疗，乳房发育有进展且无性别焦虑。然而，她的周围神经病变变得更加明显，神经传导研究（NCS）表明神经传导速度和动作电位降低。此外，她还患有肥胖、胰岛素抵抗、脂肪肝和胃溃疡等并发症。在本研究中，我们报告了一例由纯合变体引起的伴有小束状神经病变的46,XY GD病例，并总结了全球范围内报告的病例。我们首次展示了此类患者中NCS变化与年龄的比较以及先前未报告的多种并发症的存在情况。
