CACNA1A – Benign paroxysmal torticollis of infancy

Benign paroxysmal torticollis of infancy (BPTI) is a rare, self-resolving paroxysmal disorder characterized by recurrent head tilt episodes. A heterozygous CACNA1A missense variant, p.Glu533Lys, was identified in two affected family members and shown to reduce CaV2.1 channel current density and impair voltage-dependent gating, consistent with a loss-of-function mechanism (PMID:24445160).

In a multi-patient series, no pathogenic CACNA1A mutations were detected in eight isolated BPTI cases; however, four additional BPTI patients with CACNA1A mutations have been reported, notably in individuals with family histories of hemiplegic migraine, episodic ataxia, or related paroxysmal syndromes (PMID:26961263). These findings suggest limited genetic support for CACNA1A in BPTI, with variable expressivity influenced by familial migraine-related phenotypes. Genetic testing for CACNA1A may be considered in BPTI cases presenting with migraine or episodic ataxia features.

References

• European journal of paediatric neurology • 2014 • A loss-of-function CACNA1A mutation causing benign paroxysmal torticollis of infancy PMID:24445160
• Journal of child neurology • 2016 • The Genetics of Benign Paroxysmal Torticollis of Infancy: Is There an Association With Mutations in the CACNA1A Gene? PMID:26961263

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