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

Autor: Casas-Alba D; Department of Pediatric Neurology and Early Stimulation Unit, Institut de Recerca, Hospital Sant Joan de Déu, Barcelona, Spain.; Department of Genetic and Molecular Medicine IPER, Institut de Recerca, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain., López-Sala L; Department of Pediatric Neurology and Early Stimulation Unit, Institut de Recerca, Hospital Sant Joan de Déu, Barcelona, Spain., Pérez-Ordóñez M; Department of Pediatric Neurology and Early Stimulation Unit, Institut de Recerca, Hospital Sant Joan de Déu, Barcelona, Spain., Mari-Vico R; Department of Pediatric Neurology and Early Stimulation Unit, Institut de Recerca, Hospital Sant Joan de Déu, Barcelona, Spain., Bolasell M; Department of Genetic and Molecular Medicine IPER, Institut de Recerca, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain., Martínez-Monseny AF; Department of Genetic and Molecular Medicine IPER, Institut de Recerca, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain., Muchart J; Department of Radiology, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain., Fernández-Fernández JM; Department de Ciències Experimentals i de la Salut, Laboratori de Fisiologia Molecular, Universitat Pompeu Fabra, Barcelona, Spain., Martorell L; Department of Genetic and Molecular Medicine IPER, Institut de Recerca, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain., Serrano M; Department of Pediatric Neurology and Early Stimulation Unit, Institut de Recerca, Hospital Sant Joan de Déu, Barcelona, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2021 Jan; Vol. 185 (1), pp. 256-260. Date of Electronic Publication: 2020 Oct 24.
DOI: 10.1002/ajmg.a.61939
Abstrakt: 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.
(© 2020 Wiley Periodicals LLC.)
Databáze: MEDLINE
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