Wong‐Spracklen, Vivien MY;
Kolesnik, Anna;
Eck, Josefine;
Sabanathan, Saras;
Spasic‐Boskovic, Olivera;
Maw, Anna;
Baker, Kate;
(2022)
Biallelic CACNA1A variants: Review of literature and report of a child with drug-resistant epilepsy and developmental delay.
American Journal of Medical Genetics Part A
, 188
(11)
pp. 3306-3311.
10.1002/ajmg.a.62960.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Biallelic CACNA1A variants: Review of literature and report of a child with drug-resistant epilepsy and developmental delay |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/ajmg.a.62960 |
| Publisher version: | https://doi.org/10.1002/ajmg.a.62960 |
| Language: | English |
| Additional information: | © 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | biallelic, CACNA1A, cerebellar atrophy, epileptic encephalopathy, intellectual disability, recessive |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10206211 |
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