Early clinical heterogeneity in choreoacanthocytosis.
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.
Lossos
Alexander
A
Department of Neurology, Hadassah-Hebrew Unviersity Hospital, Jerusalem, Israel. alos@hadassah.org.il
Dobson-Stone
Carol
C
Monaco
Anthony P
AP
Soffer
Dov
D
Rahamim
Ezra
E
Newman
J P
JP
Mohiddin
Saidi
S
Fananapazir
Lameh
L
Lerer
Israela
I
Linetsky
Eduard
E
Reches
Avinoam
A
Argov
Zohar
Z
Abramsky
Oded
O
Gadoth
Natan
N
Sadeh
Menachem
M
Gomori
John M
JM
Boher
Moshe
M
Meiner
Vardiella
V
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
D011506:Proteins; C429654:VPS13A protein, human; D033921:Vesicular Transport Proteins