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Expanding clinical phenotype in CACNA1C related disorders: From neonatal onset severe epileptic encephalopathy to late‐onset epilepsy
Author(s) -
Bozarth Xiuhua,
Dines Jennifer N.,
Cong Qian,
Mirzaa Ghayda M.,
Foss Kimberly,
Lawrence Merritt J.,
Thies Jenny,
Mefford Heather C.,
Novotny Edward
Publication year - 2018
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.40657
Subject(s) - epilepsy , missense mutation , medicine , exome sequencing , encephalopathy , pediatrics , brugada syndrome , epilepsy syndromes , cardiomyopathy , phenotype , genetics , gene , biology , psychiatry , heart failure
CACNA1C (NM_000719.6) encodes an L‐type calcium voltage‐gated calcium channel (Ca v 1.2), and pathogenic variants have been associated with two distinct clinical entities: Timothy syndrome and Brugada syndrome. Thus far, CACNA1C has not been reported as a gene associated with epileptic encephalopathy and is less commonly associated with epilepsy. We report three individuals from two families with variants in CACNA1C . Patient 1 presented with neonatal onset epileptic encephalopathy (NOEE) and was found to have a de novo missense variant in CACNA1C (c.4087G>A (p.V1363M)) on exome sequencing. In Family 2, Patient 2 presented with congenital cardiac anomalies and cardiomyopathy and was found to have a paternally inherited splice site variant, c.3717+1_3717+2insA, on a cardiomyopathy panel. Her father, Patient 3, presented with learning difficulties, late‐onset epilepsy, and congenital cardiac anomalies. Family 2 highlights variable expressivity seen within a family. This case series expands the clinical and molecular phenotype of CACNA1C ‐related disorders and highlights the need to include CACNA1C on epilepsy gene panels.