Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.
Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India.
Parkinsonism Relat Disord. 2024 Jul;124:107012. doi: 10.1016/j.parkreldis.2024.107012. Epub 2024 May 16.
Variants in the TUBB4A gene are associated with dystonia (DYT-TUBB4A), Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H-ABC) and spastic paraplegia. Phenotypes intermediate to these three broad phenotypes are also observed. These are rare disorders, and data from diverse populations remains limited. We report seven Indian cases with dystonia phenotype related to TUBB4A mutation.
Among these seven patients, age at onset ranged from 5 to 48 years. Five patients had cranio-cervical onset of dystonia. One patient had prominent parkinsonism with dystonia. Patients responded well to botulinum toxin injected for laryngeal, cervical and jaw dystonia. The patient with parkinsonism responded well to levodopa, albeit with development of dyskinesias. Apart from the common p.Arg2Gly variant in three patients with DYT-TUBB4A, other variants included p.Arg262Pro, p.Arg39Cys and p.Asp245Asn.
We report the first collection of cases with TUBB4A mutation from India. We expand the phenotype to include levodopa-responsive parkinsonism. Indian patients, consistent with global literature, harbor prominent adductor dysphonia, cervical and jaw dystonia, which responds well to botulinum treatment.
TUBB4A 基因突变与肌张力障碍(DYT-TUBB4A)、基底节和小脑萎缩伴脑白质发育不良(H-ABC)和痉挛性截瘫有关。也观察到这三种广泛表型之间的中间表型。这些都是罕见疾病,来自不同人群的数据仍然有限。我们报告了 7 例与 TUBB4A 突变相关的肌张力障碍表型的印度病例。
这 7 名患者中,发病年龄从 5 岁到 48 岁不等。5 名患者为颅颈型肌张力障碍。1 名患者以肌张力障碍为主伴有帕金森病。患者对喉、颈和颌部的肉毒毒素注射反应良好。伴有帕金森病的患者对左旋多巴反应良好,尽管出现了运动障碍。除了 3 例 DYT-TUBB4A 患者常见的 p.Arg2Gly 变异外,其他变异包括 p.Arg262Pro、p.Arg39Cys 和 p.Asp245Asn。
我们报告了印度首例 TUBB4A 突变病例的收集。我们将表型扩展为包括左旋多巴反应性帕金森病。与全球文献一致,印度患者存在明显的内收性发音困难、颈和颌部的肌张力障碍,对肉毒毒素治疗反应良好。