性腺机能减退和小脑共济失调的关联在1908年由GordonHolmes首次认识到。由于开创性的描述,已经报道了几种异质表型,发病年龄不同,关联特征,和促性腺激素水平。在过去的十年里,这些疾病的遗传基础正在逐渐被发现。这里,我们回顾了与共济失调和性腺功能减退症相关的疾病以及相应的致病基因。在本研究的第一部分,我们重点关注与共济失调和性腺功能减退相关的临床综合征和基因(RNF216,STUB1,PNPLA6,AARS2,SIL1,SETX)。在第二部分,我们提到临床综合征和基因(POLR3A,CLPP,ERAL1HARS,HSD17B4,LARS2,TWNK,POLG,ATM,WFS1,PMM2,FMR1)与复杂表型相关,包括,在其他特征中,共济失调和性腺功能减退.我们提出了一种共济失调和性腺功能减退患者的诊断算法,我们讨论了可能的常见病因机制。
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.