Panda Prateek Kumar, Sharawat Indar Kumar, Dawman Lesa
Division of Pediatric Neurology, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.
Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
J Pediatr Genet. 2020 Nov 25;11(2):99-109. doi: 10.1055/s-0040-1721084. eCollection 2022 Jun.
Spinocerebellar ataxias (SCAs) are heterogeneous disorders with multiple genetic etiology. Mutations in the gene are associated with spinocerebellar ataxia type 18 (SCA-18). We report the first Indian case of SCA-18. The proband is a 7-year-old boy with motor delay, cerebellar signs, and cerebellar atrophy. Whole exome and direct sequencing identified compound heterozygous mutations of the coding and noncoding regions of the gene. A literature review of the published cases with pathogenic variants was performed. Beside our patients, 32 cases were identified. The majority of reported cases were males, of consanguineous kindreds, with autosomal recessive inheritance. However, a proportion of cases (39%) had autosomal dominant/semidominant inheritance with heterozygous variants. In addition to childhood-onset cerebellar ataxia, other reported features were: early-onset dementia, complicated spastic paraparesis, retinal dystrophy, hearing loss, lower motor neuron signs, and severe global developmental delay in some homozygous cases. Cerebellar atrophy was the commonest neuroimaging finding, with few cases demonstrating brain stem, supratentorial, and white matter abnormalities. Although SCA-18 should be suspected in patients with early-onset cerebellar ataxia, eye movement abnormalities, and motor delay, clinicians should be aware of late-onset, variable presentations with pyramidal signs, dementia, and hearing loss. In suspected cases, if mutations were not detected by whole-exome sequencing, direct sequencing of noncoding regions and chromosomal microarray should be considered.
脊髓小脑共济失调（SCAs）是具有多种遗传病因的异质性疾病。该基因的突变与18型脊髓小脑共济失调（SCA - 18）相关。我们报告了首例印度籍SCA - 18病例。先证者是一名7岁男孩，有运动发育迟缓、小脑体征和小脑萎缩。全外显子组测序和直接测序确定了该基因编码区和非编码区的复合杂合突变。对已发表的具有致病变异病例的文献进行了综述。除我们的患者外，共确定了32例病例。大多数报告病例为男性，来自近亲家族，呈常染色体隐性遗传。然而，一部分病例（39%）具有常染色体显性/半显性遗传，携带杂合变异。除儿童期起病的小脑共济失调外，其他报告的特征包括：早发性痴呆、复杂性痉挛性截瘫、视网膜营养不良、听力丧失、下运动神经元体征，以及一些纯合子病例出现严重的全面发育迟缓。小脑萎缩是最常见的神经影像学表现，少数病例显示脑干、幕上和白质异常。虽然对于早发性小脑共济失调、眼球运动异常和运动发育迟缓的患者应怀疑SCA - 18，但临床医生应意识到其可能有迟发性、表现多样，伴有锥体束征、痴呆和听力丧失。在疑似病例中，如果全外显子组测序未检测到突变，则应考虑对非编码区进行直接测序和染色体微阵列分析。
