CACNA1A Mutation Linking Hemiplegic Migraine and Alternating Hemiplegia of Childhood

Abstract

Familial hemiplegic migraine (FHM) and alternating hemiplegia of childhood (AHC) are severe neurological disorders that share clinical features. Therefore, FHM genes are candidates for AHC. We performed mutation analysis in the CACNA1A gene in a monozygotic twin pair with clinical features overlapping with both AHC and FHM and identified a novel de novo CACNA1A mutation. We provide the first evidence that a CACNA1A mutation can cause atypical AHC, indicating an overlap of molecular mechanisms causing AHC and FHM. These results also suggest that CACNA1A mutation scanning is indicated in patients with a severe neurological phenotype that includes paroxysmal (alternating) hemiplegia.

A novel mutation in CACNA1A associated with hemiplegic migraine, cerebellar dysfunction and late-onset cognitive decline

“…(ii) The onset of cognitive dysfunction temporally coincided with the development of the cerebellar syndrome. (iii) Cognitive disturbances are a well-known and established feature of FHM and have been described in pedigrees with FHM2 [3,8,10], FHM1 [7,[11][12][13] and a monocygotic twin pair with clinical features overlapping with both FHM and alternating hemiplegia of childhood caused by a de novo mutation in the FHM1 gene CACNA1A [14]. However, as opposed to the late onset in our proband, mental retardation with onset in childhood or early youth is typically reported.…”

Alternating Hemiplegia of Childhood: Early Characteristics and Evolution of a Neurodevelopmental Syndrome

“…[17][18][19] Episodes in subjects with AHC parallel those seen in migraine syndromes in many respects, including the character of the observed perfusion abnormalities documented on SPECT scans. [20][21][22][23] In addition, triggers common to typical migraine, including menses, chocolate, and fatigue, are common to patients with AHC, as is the symptomatic improvement with sleep.…”

Alternating Hemiplegia of Childhood in Chinese Following Long-Term Treatment With Flunarizine or Topiramate

“…AHC once was considered to be some kind of genetically determined channelopathy. Calcium channel genes such as CACNA1A (calcium channel, voltage dependent, P/Q type, alpha-1A subunit) or ATP1A2 (ATPase, Na + /K + transporting, alpha-2 polypeptide) gene mutation are involved in AHC etiology [9,10]. Therefore, flunarizine, a blocker of voltage-dependent calcium channels, has been used in management of AHC.…”