Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Via Sergio Pansini 5, 80131, Naples, Italy.
Department of Endocrinology and Reproductive Diseases, Paris-Saclay University, Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicetre, Paris, France.
Cerebellum. 2024 Apr;23(2):688-701. doi: 10.1007/s12311-023-01549-x. Epub 2023 Mar 30.
The association of hypogonadism and cerebellar ataxia was first recognized in 1908 by Gordon Holmes. Since the seminal description, several heterogeneous phenotypes have been reported, differing for age at onset, associated features, and gonadotropins levels. In the last decade, the genetic bases of these disorders are being progressively uncovered. Here, we review the diseases associating ataxia and hypogonadism and the corresponding causative genes. In the first part of this study, we focus on clinical syndromes and genes (RNF216, STUB1, PNPLA6, AARS2, SIL1, SETX) predominantly associated with ataxia and hypogonadism as cardinal features. In the second part, we mention clinical syndromes and genes (POLR3A, CLPP, ERAL1, HARS, HSD17B4, LARS2, TWNK, POLG, ATM, WFS1, PMM2, FMR1) linked to complex phenotypes that include, among other features, ataxia and hypogonadism. We propose a diagnostic algorithm for patients with ataxia and hypogonadism, and we discuss the possible common etiopathogenetic mechanisms.
性腺功能减退症与小脑性共济失调的关联于 1908 年由 Gordon Holmes 首次提出。自开创性描述以来，已经报道了几种不同的表型，其特征为发病年龄、相关特征和促性腺激素水平不同。在过去的十年中，这些疾病的遗传基础正在逐步被揭示。在这里，我们回顾了与共济失调和性腺功能减退相关的疾病以及相应的致病基因。在本研究的第一部分，我们重点介绍了主要与共济失调和性腺功能减退作为主要特征相关的临床综合征和基因（RNF216、STUB1、PNPLA6、AARS2、SIL1、SETX）。在第二部分，我们提到了与包括共济失调和性腺功能减退在内的复杂表型相关的临床综合征和基因（POLR3A、CLPP、ERAL1、HARS、HSD17B4、LARS2、TWNK、POLG、ATM、WFS1、PMM2、FMR1）。我们为患有共济失调和性腺功能减退的患者提出了一个诊断算法，并讨论了可能的共同病因发病机制。
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