肌阵挛
张力减退
表型
共济失调
肌张力障碍
步态共济失调
神经科学
运动障碍
帕金森病
进行性肌阵挛性癫痫
舞蹈病
遗传学
生物
医学
基因
病理
疾病
作者
Laura Williams,Sophie Waller,Jessica Qiu,Emily Amy Innes,Noha Elserafy,Peter G. Procopis,Hugo Sampaio,Neil Mahant,Michel Tchan,Shekeeb S. Mohammad,Hugo Morales‐Briceño,Victor S.C. Fung
摘要
Abstract Background Variants in dehydrodolichol diphosphate synthetase ( DHDDS ) and nuclear undecaprenyl pyrophosphate synthase 1 ( NUS1 ) cause a neurodevelopmental disorder, classically with prominent epilepsy. Recent reports suggest a complex movement disorder and an overlapping phenotype has been postulated due to their combined role in dolichol synthesis. Cases We describe three patients with heterozygous variants in DHDDS and five with variants affecting NUS1 . They bear a remarkably similar phenotype of a movement disorder dominated by multifocal myoclonus. Diagnostic clues include myoclonus exacerbated by action and facial involvement, and slowly progressive or stable, gait ataxia with disproportionately impaired tandem gait. Myoclonus is confirmed with neurophysiology, including EMG of facial muscles. Literature Review Ninety‐eight reports of heterozygous variants in DHDDS, NUS1 and chromosome 6q22.1 structural alterations spanning NUS1 , confirm the convergent phenotype of hypotonia at birth, developmental delay, multifocal myoclonus, ataxia, dystonia and later parkinsonism with or without generalized epilepsy. Other features include periodic exacerbations, stereotypies, anxiety, and dysmorphisms. Although their gene products contribute to dolichol biosynthesis, a key step in N‐glycosylation, transferrin isoform profiles are typically normal. Imaging is normal or non‐specific. Conclusions Recognition of their shared phenotype may expedite diagnosis through chromosomal microarray and by including DHDDS/NUS1 in movement disorder gene panels.
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