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Review
. 2024 Apr;23(2):688-701.
doi: 10.1007/s12311-023-01549-x. Epub 2023 Mar 30.

Ataxia and Hypogonadism: a Review of the Associated Genes and Syndromes

Giovanna De Michele  1 , Luigi Maione  2 , Sirio Cocozza  3 , Mario Tranfa  3 , Chiara Pane  4 , Daniele Galatolo  5 , Anna De Rosa  4 , Giuseppe De Michele  4 , Francesco Saccà  4 , Alessandro Filla  4
Affiliations
Review

Ataxia and Hypogonadism: a Review of the Associated Genes and Syndromes

Giovanna De Michele et al. Cerebellum. 2024 Apr.

Abstract

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.

Keywords: Ataxia; Gordon Holmes syndrome; Hypogonadism; NGS.

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References

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