Early-onset severe spinocerebellar ataxia 42 with neurodevelopmental deficits (SCA42ND): Case report, pharmacological trial, and literature review
- PMID: 33098379
- DOI: 10.1002/ajmg.a.61939
Early-onset severe spinocerebellar ataxia 42 with neurodevelopmental deficits (SCA42ND): Case report, pharmacological trial, and literature review
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.
© 2020 Wiley Periodicals LLC.
Similar articles
-
De novo mutation screening in childhood-onset cerebellar atrophy identifies gain-of-function mutations in the CACNA1G calcium channel gene.Brain. 2018 Jul 1;141(7):1998-2013. doi: 10.1093/brain/awy145. Brain. 2018. PMID: 29878067
-
Infantile-Onset Syndromic Cerebellar Ataxia and CACNA1G Mutations.Pediatr Neurol. 2020 Mar;104:40-45. doi: 10.1016/j.pediatrneurol.2019.09.005. Epub 2019 Oct 19. Pediatr Neurol. 2020. PMID: 31836334
-
Zonisamide can ameliorate the voltage-dependence alteration of the T-type calcium channel CaV3.1 caused by a mutation responsible for spinocerebellar ataxia.Mol Brain. 2020 Nov 26;13(1):163. doi: 10.1186/s13041-020-00700-7. Mol Brain. 2020. PMID: 33243296 Free PMC article.
-
A case of a novel CACNA1G mutation from a Chinese family with SCA42: A case report and literature review.Medicine (Baltimore). 2018 Sep;97(36):e12148. doi: 10.1097/MD.0000000000012148. Medicine (Baltimore). 2018. PMID: 30200108 Free PMC article. Review.
-
A Novel Homozygous Mutation in SPTBN2 Leads to Spinocerebellar Ataxia in a Consanguineous Family: Report of a New Infantile-Onset Case and Brief Review of the Literature.Cerebellum. 2018 Jun;17(3):276-285. doi: 10.1007/s12311-017-0893-2. Cerebellum. 2018. PMID: 29196973 Review.
Cited by
-
Characterizing Genotypes and Phenotypes Associated with Dysfunction of Channel-Encoding Genes in a Cohort of Patients with Intellectual Disability.Arch Iran Med. 2022 Dec 1;25(12):788-797. doi: 10.34172/aim.2022.124. Arch Iran Med. 2022. PMID: 37543906 Free PMC article.
-
T-type calcium channels as therapeutic targets in essential tremor and Parkinson's disease.Ann Clin Transl Neurol. 2023 Apr;10(4):462-483. doi: 10.1002/acn3.51735. Epub 2023 Feb 4. Ann Clin Transl Neurol. 2023. PMID: 36738196 Free PMC article. Review.
References
REFERENCES
-
- 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.
-
- 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.
-
- Grünewald, S., Matthijs, G., & Jaeken, J. (2002). Congenital disorders of glycosylation: A review. Pediatric Research, 52, 618-624.
-
- 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.
-
- Kito, M., Maehara, M., & Watanabe, K. (1996). Mechanisms of T-type calcium channel blockade by zonisamide. Seizure, 5, 115-119.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases