title: Phenotypic variability in a four generation family with a p.Thr666Met CACNA1A gene mutation.
abstract: BACKGROUND
  Familial hemiplegic migraine type 1, episodic ataxia type 2, and spinocerebellar ataxia type 6 are distinct neurological disorders associated with mutations in the CACNA1A gene. Phenotypic variability and clinical overlap are recognized.
  
  
  METHODS
  We describe a 2-year-old child with transiently decreased consciousness and clinical and radiological signs of early-onset cerebellar atrophy. The family history was significant, and 11 affected members across four generations indicated an unusually wide clinical spectrum including migraine, hemiplegia, coma, and progressive cerebellar ataxia.
  
  
  RESULTS
  The p.Thr666Met mutation of the CACNA1A gene was identified in the index patient and in five of his affected relatives who were analyzed. Our patient is the youngest one of this entity diagnosed to date.
  
  
  CONCLUSIONS
  Taking into account such a wide clinical expression of these gene mutations, it could be more accurate to speak about "channel-related diseases" to characterize the clinical expression according to the genetic analysis and to the phenotypes associated with each CACNA1A gene mutation.
authors.affiliation: Department of Paediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain. Electronic address: mariagbaro@gmail.com.
authors.forename: María
authors.initials: M
authors.lastname: García-Baró-Huarte
authors.affiliation: Department of Neurology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Iglesias-Mohedano
authors.affiliation: Department of Paediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Slöcker-Barrio
authors.affiliation: Section of Neuropaediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Vázquez-López
authors.affiliation: Department of Paediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: García-Morín
authors.affiliation: Section of Neuropaediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: María Concepción
authors.initials: MC
authors.lastname: Miranda-Herrero
authors.affiliation: Section of Neuropaediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Castro-Castro
mesh_terms: D015220:Calcium Channels / Q000235:genetics*; D002524:Cerebellar Ataxia / Q000235:genetics; D053447:Channelopathies / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D002675:Child, Preschool; D003128:Coma / Q000235:genetics; D006429:Hemiplegia / Q000235:genetics; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type
keywords: CACNA1A; ataxia; calcium channel; cerebellar dysfunction; hemiplegic migraine; phenotype