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Case Reports
. 2021 Jan;185(1):256-260.
doi: 10.1002/ajmg.a.61939. Epub 2020 Oct 24.

Early-onset severe spinocerebellar ataxia 42 with neurodevelopmental deficits (SCA42ND): Case report, pharmacological trial, and literature review

Dídac Casas-Alba  1   2 , Laura López-Sala  1 , Marta Pérez-Ordóñez  1 , Rosanna Mari-Vico  1 , Mercè Bolasell  2 , Antonio F Martínez-Monseny  2 , Jordi Muchart  3 , José M Fernández-Fernández  4 , Loreto Martorell  2   5 , Mercedes Serrano  1   5
Affiliations
Case Reports

Early-onset severe spinocerebellar ataxia 42 with neurodevelopmental deficits (SCA42ND): Case report, pharmacological trial, and literature review

Dídac Casas-Alba et al. Am J Med Genet A. 2021 Jan.

Abstract

Early-onset severe spinocerebellar ataxia 42 with neurodevelopmental deficits (SCA42ND, MIM#604065) is an ultrarare autosomal dominant syndrome related to de novo CACNA1G gain-of-function pathogenic variants. All patients with SCA42ND show cerebellar atrophy and/or hypoplasia on neuroimaging and share common features such as dysmorphic features, global developmental delay, and axial hypotonia, all manifesting within the first year of life. To date, only 10 patients with SCA42ND have been reported with functionally confirmed gain-of-function variants, bearing either of two recurrent pathogenic variants. We describe a girl with congenital ataxia, without epilepsy, and a de novo p.Ala961Thr pathogenic variant in CACNA1G. We review the published subjects with the aim of better characterizing the dysmorphic features that may be crucial for clinical recognition of SCA42ND. Cerebellar atrophy, together with digital anomalies, particularly broad thumbs and/or halluces, should lead to clinical suspicion of this disease. We describe the first pharmacological attempt to treat a patient with SCA42ND using zonisamide, an antiepileptic drug with T-type channel blocker activity, in an off-label indication using an itemized study protocol. No efficacy was observed at the dose tested. However, without pharmacological treatment, she showed a positive evolution in neurodevelopment during the follow-up.

Keywords: CACNA1G; T-type calcium channel blockers; broad hallux; early-onset severe spinocerebellar ataxia 42 with neurodevelopmental deficits (SCA42ND); zonisamide.

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REFERENCES

    1. Barresi, S., Dentici, M. L., Manzoni, F., Bellacchio, E., Agolini, E., Pizzi, S., … Tartaglia, M. (2020). Infantile-onset syndromic cerebellar ataxia and CACNA1G mutations. Pediatric Neurology, 104, 40-45.
    1. Chemin, J., Siquier-Pernet, K., Nicouleau, M., Barcia, G., Ahmad, A., Medina-Cano, D., … Cantagrel, V. (2018). De novo mutation screening in childhood-onset cerebellar atrophy identifies gain-of-function mutations in the CACNA1G calcium channel gene. Brain, 141, 1998-2013.
    1. Grünewald, S., Matthijs, G., & Jaeken, J. (2002). Congenital disorders of glycosylation: A review. Pediatric Research, 52, 618-624.
    1. Hara, N., Nezu, T., Kobatake, K., Morino, H., Kawakami, H., & Maruyama, H. (2019). Treatment of intractable resting tremor of spinocerebellar ataxia 42 with zonisamide. Journal of the Neurological Sciences, 396, 119-120.
    1. Kito, M., Maehara, M., & Watanabe, K. (1996). Mechanisms of T-type calcium channel blockade by zonisamide. Seizure, 5, 115-119.

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