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Biallelic CACNA1A variants: Review of literature and report of a child with drug‐resistant epilepsy and developmental delay
Biallelic variants in CACNA1A have previously been reported in nine individuals (four families) presenting with epilepsy and cognitive impairments of variable severity and age‐of‐onset. Here, we describe a child who presented at 6 months of age with drug‐resistant epilepsy and developmental delay. A...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9826308/ https://www.ncbi.nlm.nih.gov/pubmed/36063114 http://dx.doi.org/10.1002/ajmg.a.62960 |
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author | Wong‐Spracklen, Vivien M. Y. Kolesnik, Anna Eck, Josefine Sabanathan, Saras Spasic‐Boskovic, Olivera Maw, Anna Baker, Kate |
author_facet | Wong‐Spracklen, Vivien M. Y. Kolesnik, Anna Eck, Josefine Sabanathan, Saras Spasic‐Boskovic, Olivera Maw, Anna Baker, Kate |
author_sort | Wong‐Spracklen, Vivien M. Y. |
collection | PubMed |
description | Biallelic variants in CACNA1A have previously been reported in nine individuals (four families) presenting with epilepsy and cognitive impairments of variable severity and age‐of‐onset. Here, we describe a child who presented at 6 months of age with drug‐resistant epilepsy and developmental delay. At 10 years of age, she has profound impairments in motor function and communication. MRI was initially unremarkable, but progressed to severe cerebellar atrophy by age 3 years. Next Generation Sequencing and panel analysis identified a maternally inherited truncating variant c.2042_2043delAG, p.(Gln681ArgfsTer100) and paternally inherited missense variant c.1693G>A, p.(Glu565Lys). In contrast to previously reported biallelic cases, parents carrying these monoallelic variants did not display clear signs of a CACNA1A‐associated syndrome. In conclusion, we provide further evidence that biallelic CACNA1A variants can cause a severe epileptic and developmental encephalopathy with progressive cerebellar atrophy, and highlight complexities of genetic counseling in such situations. |
format | Online Article Text |
id | pubmed-9826308 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98263082023-01-09 Biallelic CACNA1A variants: Review of literature and report of a child with drug‐resistant epilepsy and developmental delay Wong‐Spracklen, Vivien M. Y. Kolesnik, Anna Eck, Josefine Sabanathan, Saras Spasic‐Boskovic, Olivera Maw, Anna Baker, Kate Am J Med Genet A Case Reports Biallelic variants in CACNA1A have previously been reported in nine individuals (four families) presenting with epilepsy and cognitive impairments of variable severity and age‐of‐onset. Here, we describe a child who presented at 6 months of age with drug‐resistant epilepsy and developmental delay. At 10 years of age, she has profound impairments in motor function and communication. MRI was initially unremarkable, but progressed to severe cerebellar atrophy by age 3 years. Next Generation Sequencing and panel analysis identified a maternally inherited truncating variant c.2042_2043delAG, p.(Gln681ArgfsTer100) and paternally inherited missense variant c.1693G>A, p.(Glu565Lys). In contrast to previously reported biallelic cases, parents carrying these monoallelic variants did not display clear signs of a CACNA1A‐associated syndrome. In conclusion, we provide further evidence that biallelic CACNA1A variants can cause a severe epileptic and developmental encephalopathy with progressive cerebellar atrophy, and highlight complexities of genetic counseling in such situations. John Wiley & Sons, Inc. 2022-09-05 2022-11 /pmc/articles/PMC9826308/ /pubmed/36063114 http://dx.doi.org/10.1002/ajmg.a.62960 Text en © 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Case Reports Wong‐Spracklen, Vivien M. Y. Kolesnik, Anna Eck, Josefine Sabanathan, Saras Spasic‐Boskovic, Olivera Maw, Anna Baker, Kate Biallelic CACNA1A variants: Review of literature and report of a child with drug‐resistant epilepsy and developmental delay |
title | Biallelic
CACNA1A
variants: Review of literature and report of a child with drug‐resistant epilepsy and developmental delay |
title_full | Biallelic
CACNA1A
variants: Review of literature and report of a child with drug‐resistant epilepsy and developmental delay |
title_fullStr | Biallelic
CACNA1A
variants: Review of literature and report of a child with drug‐resistant epilepsy and developmental delay |
title_full_unstemmed | Biallelic
CACNA1A
variants: Review of literature and report of a child with drug‐resistant epilepsy and developmental delay |
title_short | Biallelic
CACNA1A
variants: Review of literature and report of a child with drug‐resistant epilepsy and developmental delay |
title_sort | biallelic
cacna1a
variants: review of literature and report of a child with drug‐resistant epilepsy and developmental delay |
topic | Case Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9826308/ https://www.ncbi.nlm.nih.gov/pubmed/36063114 http://dx.doi.org/10.1002/ajmg.a.62960 |
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