Timothy syndrome associated with a novel likely pathogenic CACNA1C variant: A neonatal case report

Timothy Syndrome (TS) is a rare multisystem channelopathy caused by pathogenic variants in CACNA1C, classically associated with severe cardiac involvement and neurodevelopmental abnormalities.Variants affecting codon 402 represent a critical functional hotspot of the CaV1.2L-type calcium channel.We report a preterm male neonate presenting with microcephaly, small anterior fontanelle, mild fetal ventriculomegaly, cardiomyopathy, bradycardia, and neonatal respiratory failure.Whole-exome sequencing identified a heterozygous likely pathogenic variant in CACNA1C (NM_000719.7:c.1205G>A;p.Gly402Asp), not previously reported in the literature but affecting a codon with established pathogenic relevance in Timothy syndrome.This case expands the genotypic and phenotypic spectrum of Timothy syndrome and highlights the importance of early clinicalgenetic correlation in neonates with severe cardiac manifestations.