Prateek Kumar Panda1, Indar Kumar Sharawat2. 1. Pediatric Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, Uttarakhand 249203, India. 2. Pediatric Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, Uttarakhand 249203, India. Electronic address: sherawatdrindar@gmail.com.
Abstract
BACKGROUND: Still, the genetic basis of a large number of cases of early-onset isolated dystonia continues to be a mystery. In recent years, many new candidate genes are being identified as putative pathogenic factors in children with isolated dystonia due to the easy availability of whole-exome sequencing. Recently biallelic mutations in the COL6A3 gene were identified as a cause of rare dystonia (DYT)-27 syndrome. Till date, only six cases of DYT27 have been reported in the literature. METHODS: We report a new case of COL6A3 mutation associated early-onset isolated dystonia-DYT27. We did a review of the previously published cases of DYT27. Citations were identified through PubMed, Embase, Web of Science and Google scholar searches using the search terms (including variations), "Dystonia-27 or DYT27" or/and "COL6A3 mutation associated early-onset isolated dystonia", combined with study filters for original research, case reports and case series. RESULTS: Next-generation sequencing in the index patient revealed two pathogenic compound heterozygous loss of function mutations in exon 10 and exon 12 of the COL6A3 gene coding for the alpha(α)3(VI) chain of type VI collagen. Together with the presented case, seven cases (five males) were available for analysis. The median age at onset was 22 years (range: 6-61). Dystonic symptoms were started from hands in five and from the neck in the remaining two patients. Five patients had favorable outcomes with trihexyphenidyl and botulinum toxin while tetrabenazine and levodopa were ineffective. CONCLUSIONS: Although it is a new entity that is only recently discovered, in future years many more new cases suffering from this particular entity are likely to be reported and the already heterogeneous clinical spectrum is likely to be further widespread in years to come.
BACKGROUND: Still, the genetic basis of a large number of cases of early-onset isolated dystonia continues to be a mystery. In recent years, many new candidate genes are being identified as putative pathogenic factors in children with isolated dystonia due to the easy availability of whole-exome sequencing. Recently biallelic mutations in the COL6A3 gene were identified as a cause of rare dystonia (DYT)-27 syndrome. Till date, only six cases of DYT27 have been reported in the literature. METHODS: We report a new case of COL6A3 mutation associated early-onset isolated dystonia-DYT27. We did a review of the previously published cases of DYT27. Citations were identified through PubMed, Embase, Web of Science and Google scholar searches using the search terms (including variations), "Dystonia-27 or DYT27" or/and "COL6A3 mutation associated early-onset isolated dystonia", combined with study filters for original research, case reports and case series. RESULTS: Next-generation sequencing in the index patient revealed two pathogenic compound heterozygous loss of function mutations in exon 10 and exon 12 of the COL6A3 gene coding for the alpha(α)3(VI) chain of type VI collagen. Together with the presented case, seven cases (five males) were available for analysis. The median age at onset was 22 years (range: 6-61). Dystonic symptoms were started from hands in five and from the neck in the remaining two patients. Five patients had favorable outcomes with trihexyphenidyl and botulinum toxin while tetrabenazine and levodopa were ineffective. CONCLUSIONS: Although it is a new entity that is only recently discovered, in future years many more new cases suffering from this particular entity are likely to be reported and the already heterogeneous clinical spectrum is likely to be further widespread in years to come.
Authors: Seba Biswal; Preetinanda Parida; Aranya Dubbudu; Indar Kumar Sharawat; Prateek Kumar Panda Journal: Ann Indian Acad Neurol Date: 2021-02-16 Impact factor: 1.383