van der Put Johanna, Daugeliene Dalia, Bergendal Åsa, Kvarnung Malin, Svenningsson Per, Paucar Martin
Department of Clinical Neuroscience (J.v.d.P., Å.B., P.S., M.P.), Karolinska Institutet; Department of Pediatric Neurology (D.D.), Sachska Child Hospital; Department of Clinical Genetics (M.K.), and Department of Neurology (P.S., M.P.), Karolinska University Hospital, Stockholm, Sweden.
Neurol Genet. 2022 May 31;8(3):e668. doi: 10.1212/NXG.0000000000000668. eCollection 2022 Jun.
Sporadic variants in ataxia genes may mimic cerebral palsy (CP). Spinocerebellar ataxia 21 (SCA21), a very rare autosomal dominant disease, was discovered to be associated with variants in the transmembrane protein 240 () gene in 2014. In this report, we present 2 patients with sporadic SCA21, one of them diagnosed with ataxic CP.
Patients provided oral and written consent. Comprehensive clinical evaluation, neuroimaging studies, review of previous psychometric evaluations, and whole-genome sequencing were applied in both cases.
Both patients presented with early-onset ataxia and exhibited mild parkinsonian features. Patient 1 experienced motor and speech delay, autism, and dyslexia, whereas patient 2 experienced dyslexia. Neuroimaging was normal in both cases. In patient 1, the previously reported pathogenic c.509C>T (Pro170Leu) variant in was detected, whereas patient 2 harbored the novel c.182_188delinsGGAT (Val61_Pro63delinsGlyMet) variant in the same gene. Both genetic variants were sporadic.
Our findings support the notion that SCA21 is a neurodevelopmental syndrome and a mimicker of ataxic CP. Both lack of a family history of ataxia and congenital presentation were reasonable arguments to consider ataxic CP. However, lack of convincing perinatal incidents, progressive symptoms, and the common presence of cerebellar atrophy should alert neurologists about SCA21.
共济失调基因的散发性变异可能会模仿脑性瘫痪（CP）。脊髓小脑共济失调21型（SCA21）是一种非常罕见的常染色体显性疾病，2014年发现它与跨膜蛋白240（TMEM240）基因的变异有关。在本报告中，我们介绍了2例散发性SCA21患者，其中1例被诊断为共济失调型CP。
患者提供了口头和书面同意书。对两例患者均进行了全面的临床评估、神经影像学研究、回顾既往心理测评结果以及全基因组测序。
两名患者均表现为早发性共济失调，并伴有轻度帕金森样特征。患者1有运动和语言发育迟缓、自闭症和诵读困难，而患者2有诵读困难。两例患者的神经影像学检查均正常。在患者1中，检测到先前报道的TMEM240基因致病性c.509C>T（Pro170Leu）变异，而患者2在同一基因中携带新的c.182_188delinsGGAT（Val61_Pro63delinsGlyMet）变异。两种基因变异均为散发性。
我们的研究结果支持以下观点，即SCA21是一种神经发育综合征，也是共济失调型CP的模仿者。缺乏共济失调家族史和先天性表现都是考虑共济失调型CP的合理依据。然而，缺乏令人信服的围产期事件、进行性症状以及小脑萎缩的普遍存在应提醒神经科医生注意SCA21。
