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Early Clinical Heterogeneity in Choreoacanthocytosis
Alexander Lossos, MD;
Carol Dobson-Stone, DPhil;
Anthony P. Monaco, MD;
Dov Soffer, MD;
Ezra Rahamim, PhD;
J. P. Newman, PhD;
Saidi Mohiddin, MD;
Lameh Fananapazir, MD;
Israela Lerer, PhD;
Eduard Linetsky, MD;
Avinoam Reches, MD;
Zohar Argov, MD;
Oded Abramsky, MD, PhD;
Natan Gadoth, MD;
Menachem Sadeh, MD;
John M. Gomori, MD;
Moshe Boher, MD;
Vardiella Meiner, MD
Arch Neurol. 2005;62:611-614.
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.
Design and Setting 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.
Author Affiliations: Department of Neurology and Agnes Ginges Center for Human Neurogenetics (Drs Lossos, Newman, Linetsky, Reches, Argov, and Abramsky) and Departments of Pathology (Dr Soffer), Human Genetics (Drs Lerer and Meiner), Radiology (Dr Gomori), and Medical Biophysics (Dr Boher), Hadassah–Hebrew University Hospital; Electron Microscopy Laboratory, Interdepartmental Equipment Unit, Hebrew University–Hadassah Medical School (Dr Rahamim); Department of Neurology, Meir General Hospital, Kfar Saba, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Dr Gadoth); and Department of Neurology, Wolfson Medical Center, Holon (Dr Sadeh), Israel; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, England (Drs Dobson-Stone and Monaco); and Inherited Cardiac Disease Section, Cardiovascular Branch, National Heart, Lung, and Blood Institute, Bethesda, Md (Drs Mohiddin and Fananapazir).
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