Objective: We report a case of complex dystonia with the rare gene- CACNA1B.

Background: CACNA1B gene has previously been reported as the cause of myoclonus- dystonia or Dystonia 23¹. The relevance of this gene to dystonia is being debated due to recent studies which state that it causes epileptic encephalopathy²

Method: A case report.

Results:
A 19 year old male born out of a non-consanguineous marriage came with history of normal developmental milestones till 5 years of age and then developed dystonia of lower limbs followed by upper limbs with no diurnal variation. He had speech arrests initially and became completely mute at the age of 9 years. He is presently bed bound with flexed posturing of all 4 limbs, making incomprehensible sounds, difficulty swallowing, bowel and bladder incontinent with an irrelevant smile and completely dependent on all activities of daily living. He has a younger sister of 17 years who is affected similarly and is bed bound. On examination, Patient was curled up in bed with sustained involuntary posturing of all 4 limbs with no myoclonus. He was very occasionally following commands and making incomprehensible sounds. He had Spasticity in all 4 limbs with reducible contractures, hyperreflexia with bilateral ankle clonus and extensor plantars. His dystonia rating scale improved significantly after starting Levodopa. Patient could sit and stand with support and was feeding well at the end of 3 months. The blood investigations like complete blood picture, peripheral smear, thyroid profile, renal function tests, liver function tests and serum ceruloplasmin were normal. MRI brain was normal. His genetic testing with NGS and Sanger revealed the presence of heterozygous missense c2681A>T variant at exon 19 in CACNA 1B gene.

Conclusion: CACNA1B gene has been previously linked to Dystonia 23 with dystonia-myoclonus¹, a type of epileptic encephalopathy² and also at a very low frequency in the general population³. The clinical phenotype in our case was of a severe generalised disabling dystonia with cognitive and behavioural decline which was partially dopa responsive unlike the reported cases in the literature. Every young patient with dystonia should be given a trial of levodopa and further identification of such cases provide more knowledge into the spectrum of diseases and manifestations associated with CACNA1B variants, as well as potential genotype-phenotype correlations.

References: 1.Groen, J. L., Andrade, A., Ritz, K., Jalalzadeh, H., Haagmans, M., Bradley, T. E. J., … Tijssen, M. A. J. (2014). CACNA1B mutation is linked to unique myoclonus-dystonia syndrome. Human Molecular Genetics, 24(4), 987–993. 2.Gorman, Kathleen & Meyer et al. (2019). Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia. The American Journal of Human Genetics. 3. Mencacci, Niccolo & R’Bibo, Lea & Bandrés Ciga, Sara & Carecchio, Miryam & Zorzi, Giovanna & Nardocci, Nardo & Garavaglia, Barbara & Batla, Amit & Bhatia, Kailash & Pittman, Alan & Hardy, John & Weissbach, Anne & Klein, Christine & Gasser, Thomas & Lohmann, Ebba & Wood, Nicholas. (2015). The CACNA1B R1389H variant is not associated with myoclonus-dystonia in a large European multicentric cohort. Human molecular genetics.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-new-complex-dystonic-presentation-of-a-rare-gene-cacna1b-and-its-response-to-levodopa/