Minifascicular neuropathy (MN) is a rare, autosomal recessive disease with prominent structural changes of peripheral nerves. So far, it has been observed in females with a 46,XY karyotype and mutations of the Desert Hedgehog (DHH) gene, thus linking MN to gonadal dysgenesis (GD) and disorders of sex development (DSD). However, a 46,XX proband with normal female sex and gender development underwent clinical evaluations, nerve conduction studies and genetic screening for a severe motor‐sensory neuropathy with a pathological phenotype that hinted at MN. Indeed, sural nerve biopsy revealed a profound disturbance of perineurium development with a thin and loose structure. High‐resolution ultrasound (HRUS) also disclosed diffuse changes of nerve echotexture that visibly correlated with the pathological features. After extensive genetic testing, a novel homozygous DHH null mutation (p.Ser185*) was identified in the proband and in her sister, who was affected by a similar motor‐sensory neuropathy, but was eventually found to be a 46,XY patient according to a late diagnosis of DSD with complete GD. DHH should therefore be considered as a possible cause of rare non‐syndromic hereditary motor‐sensory neuropathies, regardless of DSD. Furthermore, HRUS could effectively smooth the complex diagnostic workup as it demonstrated a high predictive power to detect MN, providing the same detailed correlations to the pathologic features of the nerve biopsy and Dhh−/− mice in both sisters. Hence, HRUS may assume a pivotal role in guiding molecular analysis in individuals with or without DSD.

中文翻译：

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与 DHH 相关的遗传性综合征性和非综合征性小束状神经病的融合病理和超声特征

小束状神经病 (MN) 是一种罕见的常染色体隐性遗传病，周围神经结构发生显着变化。到目前为止，它已在具有 46,XY 核型和沙漠刺猬 ( DHH)突变的雌性中观察到) 基因，从而将 MN 与性腺发育不全 (GD) 和性发育障碍 (DSD) 联系起来。然而，一名 46,XX 女性性别和性别发育正常的先证者接受了临床评估、神经传导研究和基因筛查，以发现具有提示 MN 病理表型的严重运动感觉神经病。事实上，腓肠神经活检显示神经束膜发育严重紊乱，结构薄而松散。高分辨率超声 (HRUS) 还揭示了与病理特征明显相关的神经回波纹理的弥漫性变化。经过广泛的基因检测，一种新型的纯合DHH在先证者和她的姐姐中发现了无效突变（p.Ser185*），她的姐姐也受了类似的运动感觉神经病的影响，但根据 DSD 的晚期诊断和完全 GD 最终被发现是一名 46,XY 患者. 因此，无论 DSD 情况如何，DHH都应被视为罕见的非综合征遗传性运动感觉神经病的可能原因。此外，HRUS 可以有效地简化复杂的诊断检查，因为它表现出检测 MN 的高预测能力，提供与两姐妹的神经活检和Dhh -/- 小鼠的病理特征相同的详细相关性。因此，HRUS 可能在指导有或没有 DSD 的个体的分子分析方面发挥关键作用。