case has been reported
13
in a patient of ‘‘middle-east-
ern’’ background, but further details of ethnic back-
ground are not reported.
In HD the parkinsonian phenotype is related to longer
trinucleotide repeat expansions, however, this does not
appear to be the case with HDL2. Three cases have
been reported with the longest expansion found to
date—59 repeats. Our Case 2 initially presented with
chorea and progressed to a dystonic and bradykinetic/
rigid phenotype; another case
14
also presented initially
with chorea, and was not reported to develop parkinson-
ism, although details of follow-up are not available; the
son of the Case 2 reported by Greenstein et al. (2007)
was parkinsonian from disease onset. Patients with 52
repeats
8
or 57 repeats
10
have been reported who pre-
sented with parkinsonism and never developed chorea
during their disease course. This suggests that the pres-
ence of the choreic or parkinsonian phenotype is inde-
pendent of the number of CAG/CTG repetitions.
The age of onset of symptoms (22 years) of Case 2 is
among the youngest reported to date. As with HD, the
age of onset is inversely related to the size of the trinu-
cleotide repeat expansion.
15
Similarly, the age of onset
of Case 3 is the oldest reported to date, and he was
found to have a trinucleotide repeat expansion at the
lower end of the pathological range. However, his rate of
disease progression was remarkably rapid, as the disease
course usually lasts 10 to 15 years
4
and it is unusual for
patients to be bedbound within 5 years of presentation.
The reason for this fast progression was not identified.
Cases 1 to 3 were diagnosed from a cohort of 29
HDL patients, defined as a phenotype of progressive
chorea, dystonia, myoclonus, or ataxia with cognitive
impairment, in whom HD was excluded. The propor-
tion of 10% of HDL cases being diagnosed with HDL2
is higher than in other reports, and is likely to be due
to the significant proportion (44.6%) of the Brazilian
population being of African descent.
16
A higher per-
centage of 26% was seen only in black South Africans
with an HDL phenotype.
17
The clinical and neuropathological
8
similarities
between HDL2 and HD suggest that they may share
pathophysiological pathways. However, in HDL2, in
contrast to HD, the phenotypes of parkinsonism or
chorea do not correlate with the size of the CAG/CTG
repeat expansion, suggesting that another unknown fac-
tor may play a role in the clinical expression of dis-
ease. In addition to the importance of correct diagnosis
for clinical management and genetic counseling, iden ti-
fication of new HDL2 patients may provide insights
into the understanding of HD and other trinucleotide
repeat disorders.
LEGENDS TO THE VIDEO
Segment 1. Patient 3 presenting dystonic postures in
his right hand and face. Lying down, involuntary jerk-
ing movements in legs and right shoulder occur.
Segment 2. Patient 4 exhibits involuntary tongue
protrusions, excessive eye blinking, head bobbing,
hyperactive deep tendon reflexes, and gait apraxia.
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2247HUNTINGTON’S DISEASE-LIKE 2 IN BRAZIL
Movement Disorders, Vol. 23, No. 15, 2008