ICNC Abstracts, ICNC 2018

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A novel mutation in KMT2B gene causing childhood-onset generalized dystonia
Tanmayee Subhash Thombare

Last modified: 2018-09-09

Abstract


Introduction:

Childhood onset dystonias are complex hyperkinetic movement disorders, etiology of which can be either inherited or acquired. With the advent of next generation sequencing, there has been a drastic increase in its identification.

A 13 year old boy presented with abnormal generalized twisting postures involving the limbs, trunk and face since 8 years of age. These movements progressed leading to torticollis and oro-mandibular dystonia causing dysarthria and dysphagia. The movements were patterned, non-rhythmic, aggravated on action and disappeared in sleep. On examination, he had grey hair, acne vulgaris, bluedot cataract and dysmorphic features. He had dysarthria, axial and appendicular dystonia with severe cervical and oro-mandibular dystonia, dystonic tremors of head, choreiform movements in upper limbs. Possibility of a childhood onset primary generalized dystonia was considered. There was no response to levodopa trial. Presently, he is on trihexyphenidyl, clonazepam and tetrabenizine at optimal doses. However, dystonia still persists.  MRI brain, nerve conduction, serum ceruloplasmin levels, plasma ammonia and lactate were normal. Brainstem evoked response audiometry showed mixed hearing loss. Targeted next generation sequencing of dystonia gene panel identified a previously unreported heterozygous missense variation in exon 24 of the KMT2B gene (chr19:36221280G>A; Depth: 99x). The pathogenecity of the variant was further confirmed by Sanger sequencing. Parental screening could not be performed. As parents were clinically asymptomatic, a diagnosis of childhood onset progressive dystonia caused due to a denovo mutation in KMT2B gene was considered.

Conclusion:  Mutations in KMT2B gene are an emerging cause of progressive childhood onset dystonia DYT28.


Keywords


dystonia

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