Novel de novo heterozygous CACNA1A gene variant in generalised dystonia: a case report

Author:

Alshareet Mohammed,Alakkas AljoharahORCID,Alsinaidi Omar A,Bawazeer Shahad,Peer-Zada Abdul Ali

Abstract

BackgroundDystonia is a genetic or non-genetic movement disorder with typical patterned and twisting movements due to abnormal muscle contractions that may be associated with tremor. Genetic and phenotypic heterogeneity leads to variable clinical presentation.MethodologyNext-generation sequencing technologies are being currently used in the workup of patients with inherited dystonia to determine the specific cause in the individuals with autosomal dominant, recessive, X-linked or mitochondrial inheritance patterns. Calcium voltage-gated channel subunit alpha1 A (CACNA1A) gene variants are rare in dystonias.ResultsWe here present a 20-year-old man with a history of delayed milestones, flexor posturing, dysarthria, dysphagia and a negative family history from consanguineous parents. Neurological examination revealed right lateral scoliosis of the neck and generalised dystonic posturing affecting both upper and lower limbs. MRI of the brain was unremarkable. Molecular genetic results revealed a heterozygous variant in the CACNA1A gene (CHR19: NM_023035.2, c. 1602G>A; p. Met534Ile). Segregation analyses in both the parents revealed wild-type CACNA1A gene suggesting de novo nature of the variant with a likely pathogenic classification.ConclusionDystonia is one of the clinical phenotypes that can be associated with CACNA1A gene mutations and we recommend that this gene either be included in the dystonia panel offered or tested when the initial primary genetic result is negative.

Publisher

BMJ

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