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

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• dc.contributor.author Casas Alba, Dídac
• dc.contributor.author López-Sala, Laura
• dc.contributor.author Pérez-Ordóñez, Marta
• dc.contributor.author Mari-Vico, Rosanna
• dc.contributor.author Bolasell, Mercè
• dc.contributor.author Martínez Monseny, Antonio Federico
• dc.contributor.author Muchart, Jordi
• dc.contributor.author Fernández-Fernández, José Manuel, 1967-
• dc.contributor.author Martorell, Loreto
• dc.contributor.author Serrano, Mercedes L.
• dc.date.accessioned 2022-02-01T07:32:44Z
• dc.date.available 2022-02-01T07:32:44Z
• dc.date.issued 2021
• dc.description.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.
• dc.description.sponsorship This work was supported by a National Grant PI17/00101 from the National R&D&I Plan, cofinanced by the Instituto de Salud Carlos III (Subdirectorate-General for Evaluation and Promotion of Health Research) and FEDER (European Regional Development Fund). M.S. is supported by the Generalitat de Catalunya (PERIS SLT008/18/00194). J.M.F-F. is supported by the Spanish Ministry of Science and Innovation, the State Research Agency (AEI, Agencia Estatal de Investigación), and FEDER Funds (Fondo Europeo de Desarrollo Regional): Grants RTI2018-094809-B-I00, and CEX2018-000792-M through the “María de Maeztu” Programme for Units of Excellence in R&D to “Departament de Ciències Experimentals i de la Salut”.
• dc.format.mimetype application/pdf
• dc.identifier.citation Casas-Alba D, López-Sala L, Pérez-Ordóñez M, Mari-Vico R, Bolasell M, Martínez-Monseny AF, Muchart J, Fernández-Fernández JM, Martorell L, Serrano M. Early-onset severe spinocerebellar ataxia 42 with neurodevelopmental deficits (SCA42ND): Case report, pharmacological trial, and literature review. Am J Med Genet A. 2021;185(1):256-60. DOI: 10.1002/ajmg.a.61939
• dc.identifier.doi http://dx.doi.org/10.1002/ajmg.a.61939
• dc.identifier.issn 1552-4825
• dc.identifier.uri http://hdl.handle.net/10230/52378
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof Am J Med Genet A. 2021;185(1):256-60
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-094809-B-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2018-000792-M
• dc.rights This is the peer reviewed version of the following article: Casas-Alba D, López-Sala L, Pérez-Ordóñez M, Mari-Vico R, Bolasell M, Martínez-Monseny AF, Muchart J, Fernández-Fernández JM, Martorell L, Serrano M. Early-onset severe spinocerebellar ataxia 42 with neurodevelopmental deficits (SCA42ND): Case report, pharmacological trial, and literature review. Am J Med Genet A. 2021;185(1):256-60. DOI: 10.1002/ajmg.a.61939, which has been published in final form at http://dx.doi.org/10.1002/ajmg.a.61939. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword CACNA1G
• dc.subject.keyword T-type calcium channel blockers
• dc.subject.keyword Broad hallux
• dc.subject.keyword Early-onset severe spinocerebellar ataxia 42 with neurodevelopmental deficits (SCA42ND)
• dc.subject.keyword Zonisamide
• dc.title Early-onset severe spinocerebellar ataxia 42 with neurodevelopmental deficits (SCA42ND): Case report, pharmacological trial, and literature review
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion