Frachet Simon, Chazelas Pauline, Magy Laurent, Cintas Pascal, Brouquières Danielle, Girardie Pierre, Espagno Louise, Melloni Boris, Guilleminault Laurent, Lia Anne-Sophie
From the Neurology Department (S.F., L.M.), University Hospital of Limoges; UR20218-NEURIT (S.F., P. Chazelas, L.M., A.-S.L.), University of Limoges; Biochemistry and Molecular Genetic Department (P. Chazelas, A.-S.L.), University Hospital of Limoges; Neurology Department (P. Cintas, P.G.); Department of Respiratory Medicine (D.B., L.G.), University Hospital of Toulouse; Neurology Department (L.E.), Cahors Hospital; and Department of Respiratory Medicine (B.M.), University Hospital of Limoges, France.
Neurol Genet. 2024 Jul 19;10(4):e200166. doi: 10.1212/NXG.0000000000200166. eCollection 2024 Aug.
Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome results from variations in and is mostly caused by intronic biallelic pathogenic expansions (RE-). Refractory chronic cough (RCC) is frequently observed for years to decades preceding ataxia onset. Whether peripheral nerves are involved in the presymptomatic phase characterized by RCC is uncertain.
Here, patients previously screened for RCC and identified as having at least one RE- intronic expansion underwent a comprehensive clinical and neurophysiologic assessment and were screened for additional exonic variations.
Fourteen patients with RCC and RE- were investigated. Seven patients presented with biallelic RE- (Bi-RE-) while 7 presented with monoallelic RE- (Mono-RE-). In patients with Mono-RE-, no additional exonic variation was identified, and clinical examinations were normal. Most of the patients with Bi-RE- presented with subtle neurologic impairment, mainly exhibiting decreased lower limb vibration sense (85.7%). Nerve conduction studies revealed that all patients with Bi-RE- exhibited lower sensory sum scores than patients with Mono-RE- (median 20.2 µV vs 84.9 µV, = 0.0012). In addition, the radial-to-sural sensory ratios were null or inverted (>0.5) in all patients but one with Bi-RE-, which is consistent with sensory neuronopathy.
Patients with Bi-RE-RFC1 already exhibit widespread sensory neuron involvement at the time of apparently isolated RCC.
小脑共济失调、神经病和前庭反射消失综合征由相关基因变异引起，主要由内含子双等位基因致病性扩增（RE-）所致。难治性慢性咳嗽（RCC）常在共济失调发作前数年至数十年出现。RCC所表征的症状前期是否累及周围神经尚不确定。
在此，对先前筛查出RCC且被确定至少有一个RE-内含子扩增的患者进行了全面的临床和神经生理学评估，并筛查了其他外显子变异。
对14例患有RCC和RE-的患者进行了研究。7例患者表现为双等位基因RE-（Bi-RE-），7例表现为单等位基因RE-（Mono-RE-）。在Mono-RE-患者中，未发现其他外显子变异，临床检查正常。大多数Bi-RE-患者存在轻微神经功能损害，主要表现为下肢振动觉减退（85.7%）。神经传导研究显示，所有Bi-RE-患者的感觉总和评分均低于Mono-RE-患者（中位数20.2 μV对84.9 μV，P = 0.0012）。此外，除1例Bi-RE-患者外，所有患者的桡神经至腓肠神经感觉比均为零或倒置（>0.5），这与感觉神经元病一致。
在明显孤立的RCC阶段，Bi-RE-RFC1患者已表现出广泛的感觉神经元受累。
