CACNA1C-related disorders explained

CACNA1C-related disorders are a group of rare diseases caused by variants in the CACNA1C gene, which encodes a subunit of the L-type voltage-dependent calcium channel. Genomic sequencing has linked a number of heterogenous phenotypes to pathogenic variants in the CACNA1C gene:^[1]

• Timothy syndrome, which may or may not occur with syndactyly
• Short QT syndrome or Brugada syndrome
• Long QT syndrome or other arrhythmia without additional symptoms.

CACNA1C-related disorders are inherited in an autosomal dominant manner. Symptoms of CACNA1C-related disorders are primarily neurological^[2] and may include developmental delay, autism or autistic features, and seizures. Facial dysmorphism may also be present.^[3]

Notes and References

1. Levy . Rebecca J. . Timothy . Katherine W. . Underwood . Jack F.G. . Hall . Jeremy . Bernstein . Jonathan A. . Pașca . Sergiu P. . January 2023 . A Cross-Sectional Study of the Neuropsychiatric Phenotype of CACNA1C-Related Disorder . Pediatric Neurology . en . 138 . 101–106 . 10.1016/j.pediatrneurol.2022.10.013. 36436328 .
2. Rodan . Lance H. . Spillmann . Rebecca C. . Kurata . Harley T. . Lamothe . Shawn M. . Maghera . Jasmine . Jamra . Rami Abou . Alkelai . Anna . Antonarakis . Stylianos E. . Atallah . Isis . Bar-Yosef . Omer . Bilan . Frédéric . Bjorgo . Kathrine . Blanc . Xavier . Van Bogaert . Patrick . Bolkier . Yoav . October 2021 . Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations . Genetics in Medicine . en . 23 . 10 . 1922–1932 . 10.1038/s41436-021-01232-8 . 8488020 . 34163037.
3. Bauer . Rosemary . Timothy . Katherine W. . Golden . Andy . 2021-05-17 . Update on the Molecular Genetics of Timothy Syndrome . Frontiers in Pediatrics . 9 . 668546 . 10.3389/fped.2021.668546 . 2296-2360 . 8165229 . 34079780. free .