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<p>Spinocerebellar ataxia 27&#xa0;A (SCA27A) is a form of progressive cerebellar ataxia due to pathogenic variants in the Fibroblast Growth Factor 14 (<i>FGF14</i>) gene. The objective of this paper is to characterise the clinical spectrum of SCA27A microdeletions (&gt; 50&#xa0;bp, &lt;2Mbp), and report two novel cases.&#xa0;Literature searches of PubMed, OMIM and ClinVar were carried out. We identified SCA27A microdeletions in 32 cases across 11 families. The phenotypic presentation is: 75% (24/32) nystagmus, 46% (15/32) ataxia, 21% (7/32) episodic ataxia, 21% (7/32) tremor, 15% (5/32) dysarthria, 34% (11/32) learning disability, 28% (8/32) neuropsychiatric disease. The presentation is variable within and between families. Episodic symptoms, nystagmus, learning disability and neuropsychiatric symptoms occur at an earlier age. Patient 1 represents the first case with a 58 kb <i>FGF14</i> deletion who presented with a paroxysmal movement disorder. Patient 2 carries a 545&#xa0;kb deletion and developed episodic ataxia and trigeminal neuralgia, a novel feature not previously described in this cohort. We report two cases of heterozygous <i>FGF14</i> microdeletions: Patient 1 (58&#xa0;kb) and Patient 2 (545&#xa0;kb), expanding the phenotypic spectrum of <i>FGF14</i> structural variants to 32 cases across 11 families. We review potential mechanism from pre-clinical studies relating <i>FGF14</i> haploinsufficiency to cerebellar, cognitive, neuropsychiatric symptoms, as well as trigeminal neuralgia. We propose the hypothesis that the episodic symptoms in SCA27A align with the molecular pathology of a channelopathy and propose management strategies based on this insight.</p>

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Spinocerebellar Ataxia 27 A with Episodic Ataxia: Case Series of Fibroblast Growth Factor 14 (FGF14) Microdeletions

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月16日

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  • Elena Conci,
  • Thomas L. Kelly,
  • Ruth Armstrong,
  • Pooja Harijan,
  • Rita Horvath

摘要

Spinocerebellar ataxia 27 A (SCA27A) is a form of progressive cerebellar ataxia due to pathogenic variants in the Fibroblast Growth Factor 14 (FGF14) gene. The objective of this paper is to characterise the clinical spectrum of SCA27A microdeletions (> 50 bp, <2Mbp), and report two novel cases. Literature searches of PubMed, OMIM and ClinVar were carried out. We identified SCA27A microdeletions in 32 cases across 11 families. The phenotypic presentation is: 75% (24/32) nystagmus, 46% (15/32) ataxia, 21% (7/32) episodic ataxia, 21% (7/32) tremor, 15% (5/32) dysarthria, 34% (11/32) learning disability, 28% (8/32) neuropsychiatric disease. The presentation is variable within and between families. Episodic symptoms, nystagmus, learning disability and neuropsychiatric symptoms occur at an earlier age. Patient 1 represents the first case with a 58 kb FGF14 deletion who presented with a paroxysmal movement disorder. Patient 2 carries a 545 kb deletion and developed episodic ataxia and trigeminal neuralgia, a novel feature not previously described in this cohort. We report two cases of heterozygous FGF14 microdeletions: Patient 1 (58 kb) and Patient 2 (545 kb), expanding the phenotypic spectrum of FGF14 structural variants to 32 cases across 11 families. We review potential mechanism from pre-clinical studies relating FGF14 haploinsufficiency to cerebellar, cognitive, neuropsychiatric symptoms, as well as trigeminal neuralgia. We propose the hypothesis that the episodic symptoms in SCA27A align with the molecular pathology of a channelopathy and propose management strategies based on this insight.