Clinical and genetic heterogeneity in benign hereditary chorea.
BACKGROUND
Benign hereditary chorea (BHC) is an autosomal dominant disorder that can be distinguished from Huntington disease by its early onset, stable or only slightly progressive course, and absence of mental deterioration. The variation in clinical features is such that its very existence has been doubted. The authors recently described the localization of a gene responsible for BHC on chromosome 14q in a large Dutch family.


OBJECTIVE
To report results of extensive clinical and linkage analyses for this Dutch family and six other families with BHC.


RESULTS
Three of the seven families had linkage to a region on chromosome 14q13.1-q21.1. HOMOG analysis showed odds of 10 x 10(11) in favor of locus heterogeneity. Haplotype analyses for the linked families resulted in a reduction of the critical interval for the BHC gene to 8.4 cM between marker D14S49 and marker D14S278. Clinically, these three families had a homogeneous picture with early-onset chorea, sometimes accompanied by slight ataxia in walking, but without dystonia, myoclonic jerks, or dysarthria. The severity of the choreatic movements tended to abate in adolescence or early adulthood. In the unlinked families, symptoms and signs were more heterogeneous as to age at onset and the occurrence of myoclonic jerks or dystonia.


CONCLUSIONS
BHC is a clinically and genetically heterogeneous disorder, with one well-defined clinical syndrome mapping to chromosome 14q.
Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands.
G J
GJ
Breedveld
A K
AK
Percy
M E
ME
MacDonald
B B A
BB
de Vries
C
C
Yapijakis
L S
LS
Dure
E F
EF
Ippel
L A
LA
Sandkuijl
P
P
Heutink
W F M
WF
Arts
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D002819:Chorea / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D018450:Disease Progression; D005190:Family; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D005820:Genetic Testing; D005838:Genotype; D006115:Greece / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D020407:Internet; D008126:Lod Score; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D012075:Remission, Spontaneous; D014481:United States / Q000453:epidemiology
D005819:Genetic Markers