Timothy syndrome

Timothy syndrome is a rare autosomal dominant disorder that causes physical malformations together with neurological and developmental problems, arising from mutations in the CACNA1C gene, which encodes a calcium channel protein. The mutations delay the channel's closing, a process called voltage-dependent inactivation, which increases cellular excitability and prolongs electrical activity in heart cells. Its most distinctive combination of features is webbing of the fingers and toes, known as syndactyly, occurring together with long QT syndrome, an unusual pairing rarely seen together in a single patient. Heart rhythm abnormalities affect about 94 percent of patients and structural heart defects appear in about 59 percent, while roughly 80 percent of survivors develop autism spectrum disorders; facial differences, dental problems and small, weak teeth are also common. Because the disorder is autosomal dominant, a single mutated gene copy is enough to cause it, and features are typically present from birth though some symptoms emerge later in childhood.