Key result
Novel CACNA1C mutation manifests as atypical Timothy syndrome with syndactyly but no QT prolongation.
Case Report (n=1)
This case expands the phenotypic spectrum of CACNA1C mutations, demonstrating that Timothy syndrome-like features can occur without the classically obligatory QT prolongation.
Extends CACNA1C phenotypic spectrum in children; hypothesis-generating and requires validation before guiding practice.
Timothy syndrome is characterized by a unique combination of a prolongation of the corrected QT interval of the electrocardiogram and bilateral cutaneous syndactyly of the fingers and the toes and is caused by heterozygous mutations in CACNA1C, a gene encoding a calcium channel. After the discovery of the CACNA1C gene as the causative gene for Timothy syndrome, patients with CACNA1C mutations with QT prolongation but without syndactyly were described. Here, we report a 5-year-old female patient with cutaneous syndactyly, developmental delay, and pulmonary hypertension. Exome analysis showed a previously undescribed de novo heterozygous mutation in the CACNA1C gene, p.Arg1024Gly. To our knowledge, this patient is the first to exhibit syndactyly and to carry a CACNA1C mutation but to not have QT prolongation, which has long been considered an obligatory feature of Timothy syndrome.
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Kosaki et al. (2018) conducted a case report in Timothy syndrome-like condition (n=1). CACNA1C gene mutation (p.Arg1024Gly) was evaluated on Presence of QT prolongation. A novel de novo heterozygous mutation in the CACNA1C gene (p.Arg1024Gly) was identified in a 5-year-old female with syndactyly but without QT prolongation, an atypical presentation for Timothy syndrome.
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