TY - JOUR
T1 - Expanding clinical phenotype in CACNA1C related disorders
T2 - From neonatal onset severe epileptic encephalopathy to late-onset epilepsy
AU - Bozarth, Xiuhua
AU - Dines, Jennifer N.
AU - Cong, Qian
AU - Mirzaa, Ghayda M.
AU - Foss, Kimberly
AU - Lawrence Merritt, J.
AU - Thies, Jenny
AU - Mefford, Heather C.
AU - Novotny, Edward
N1 - Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2018/12
Y1 - 2018/12
N2 - 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.
AB - 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.
KW - CACNA1C
KW - electroencephalogram
KW - epileptic encephalopathy
KW - exome sequencing
KW - neonatal onset epileptic encephalopathy
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U2 - 10.1002/ajmg.a.40657
DO - 10.1002/ajmg.a.40657
M3 - Article
C2 - 30513141
AN - SCOPUS:85057714411
SN - 1552-4825
VL - 176
SP - 2733
EP - 2739
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 12
ER -