title: Early clinical heterogeneity in choreoacanthocytosis.
abstract: BACKGROUND
  Choreoacanthocytosis (CHAC) is a slowly progressive multisystem disorder with involuntary movements, cognitive decline, behavioral changes, seizures, and polyneuropathy caused by mutations in the VPS13A gene.
  
  
  OBJECTIVE
  To describe the early clinical features and possible genotype-phenotype correlation in CHAC.
  
  
  METHODS
  Case series in a tertiary care center. PATIENTS AND MAIN OUTCOME METHODS: Choreoacanthocytosis was diagnosed in 3 patients of Jewish origin from 3 unrelated families. We reviewed their medical histories and performed molecular analysis by screening all 73 exons of VPS13A.
  
  
  RESULTS
  Trichotillomania, hypertrophic cardiomyopathy, and idiopathic hyperCKemia, in 1 patient each, preceded the development of the full clinical spectrum of CHAC by 2 to 20 years. At diagnosis, 2 patients manifested signs of overt neuromuscular involvement and were homozygous for the 6059delC mutation, whereas 1 patient had only hyporeflexia and was homozygous for the EX23del mutation. Because only 1 of the 2 patients with 6059delC had cardiomyopathy, its relevance to CHAC is unclear.
  
  
  CONCLUSIONS
  These findings extend the knowledge of significant early clinical heterogeneity in CHAC and suggest a possible genotype-phenotype correlation. Awareness of the early manifestations may prevent misdiagnosis and enable appropriate genetic counseling.
authors.affiliation: Department of Neurology, Hadassah-Hebrew Unviersity Hospital, Jerusalem, Israel. alos@hadassah.org.il
authors.forename: Alexander
authors.initials: A
authors.lastname: Lossos
authors.forename: Carol
authors.initials: C
authors.lastname: Dobson-Stone
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Monaco
authors.forename: Dov
authors.initials: D
authors.lastname: Soffer
authors.forename: Ezra
authors.initials: E
authors.lastname: Rahamim
authors.forename: J P
authors.initials: JP
authors.lastname: Newman
authors.forename: Saidi
authors.initials: S
authors.lastname: Mohiddin
authors.forename: Lameh
authors.initials: L
authors.lastname: Fananapazir
authors.forename: Israela
authors.initials: I
authors.lastname: Lerer
authors.forename: Eduard
authors.initials: E
authors.lastname: Linetsky
authors.forename: Avinoam
authors.initials: A
authors.lastname: Reches
authors.forename: Zohar
authors.initials: Z
authors.lastname: Argov
authors.forename: Oded
authors.initials: O
authors.lastname: Abramsky
authors.forename: Natan
authors.initials: N
authors.lastname: Gadoth
authors.forename: Menachem
authors.initials: M
authors.lastname: Sadeh
authors.forename: John M
authors.initials: JM
authors.lastname: Gomori
authors.forename: Moshe
authors.initials: M
authors.lastname: Boher
authors.forename: Vardiella
authors.initials: V
authors.lastname: Meiner
mesh_terms: D000328:Adult; D017668:Age of Onset; D002819:Chorea / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004252:DNA Mutational Analysis; D003951:Diagnostic Errors / Q000517:prevention & control; D018450:Disease Progression; D005091:Exons / Q000235:genetics; D005260:Female; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D020271:Heredodegenerative Disorders, Nervous System / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D006720:Homozygote; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011237:Predictive Value of Tests; D011506:Proteins / Q000235:genetics; D033921:Vesicular Transport Proteins
chemical_list: D011506:Proteins; C429654:VPS13A protein, human; D033921:Vesicular Transport Proteins