<unk>  has an autosomal-dominant pattern of inheritance. There are two recognized types of<unk> , classical (type-1) and atypical (type-2). They are both caused by mutations in CACNA1C, the gene encoding the calcium channel Cav1.2 α subunit.<unk>  mutations in CACNA1C cause delayed channel closing, thus increased cellular excitability. Both classical and atypical<unk> s are caused by mutations in CACNA1C. These mutations are in exon 8 (atypical form) and exon 8a (classical form), an alternatively spliced exon. Exon 8a is highly expressed in the heart, brain, gastrointestinal system, lungs, immune system, and smooth muscle. Exon 8 is also expressed in these regions and its level is roughly five-fold higher than exon 8a expression. One mutation is found in patients with classical<unk> , G406R, located just past the sixth membrane-spanning segment of domain 1 (D1S6). The conserved glycine at this position seems to be vital for proper voltage-dependent inactivation, as the mutant is lacking in this respect. Atypical<unk>  mutations are similar, one being the identical G406R mutation in the other splice form and the second mutation being G402S, located a few amino acids upstream. The effect of these mutations on channel function is identical to the G406R mutation in classical<unk> . The lack of proper voltage-dependent inactivation in these mutants causes prolonged inward current and depolarization during cardiac action potentials. This leads to long QT syndrome and resultant arrhythmia. Because exon 8 has greater expression in the heart versus exon 8a, patients with atypical<unk>  have worsened cardiac defects compared to those with the classical form.
Timothy syndrome
Goldenhar syndrome
Joubert syndrome
Wolfram syndrome
Christianson syndrome
Cohen syndrome
Kaufman oculocerebrofacial syndrome
Karak syndrome