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Clinical and Molecular Correlations in Spinocerebellar Ataxia Type 6
A Study of 24 Dutch Families
Richard J. Sinke, PhD;
Elly F. Ippel, MD;
Conny M. Diepstraten, BSc;
Frits A. Beemer, MD, PhD;
John H. J. Wokke, MD, PhD;
Bob J. van Hilten, MD, PhD;
Nine V. A. M. Knoers, MD, PhD;
Hans Kristian Ploos van Amstel, PhD;
H. P. H. Kremer, MD, PhD
Arch Neurol. 2001;58:1839-1844.
Background Autosomal dominant cerebellar ataxias (ADCAs),
or spinocerebellar ataxias (SCAs), are a heterogeneous group of
neurodegenerative disorders. Mild CAG repeat expansions in the
 1A voltage–dependent calcium channel gene are
associated with SCA type 6 (SCA6).
Objective To obtain further insight into the contribution of
SCA6 mutations to the phenotypic variability in Dutch patients
with ataxia.
Design Survey and case series.
Setting Hospitalized care, referral center.
Patients and Methods The SCA6 locus was analyzed for
CAG repeat expansions in a referred sample of 220 Dutch families with
progressive cerebellar ataxia. Clinical characteristics of patients
with SCA6 were investigated and correlated with molecular findings.
Results The diagnosis SCA6 was confirmed in 24 families
comprising 30 familial and 4 sporadic cases. Mean ± SD
age at onset was 50.1 ± 11.1 years. Expanded CAG repeats
with sizes 22, 23, and 25 were found. These sizes correlated inversely
with age at onset. No intergenerational changes in CAG repeat size were
detected. Despite this, 2 families showed clinical anticipation.
Conclusions This study provides the first detailed description
of Dutch patients with SCA6. Clinical analysis identifies SCA6 as a
late-onset ataxia in which eye movement abnormalities are prominent and
consistent early manifestations. No single clinical sign can be
considered specific for SCA6. Some patients have ataxia combined with
episodic headaches or nausea, suggesting an overlap among SCA6,
eposidic ataxia type 2, and familial hemiplegic migraine.
Spinocerebellar ataxia type 6 accounts for approximately 11% of all
Dutch families with ADCA. Analysis of SCA6 contributes further to the
genetic classification of patients with ADCA, including patients
without a clear family history of the disease.
From the Departments of Medical Genetics (Drs
Sinke, Ippel, Diepstraten, Beemer,
and Ploos van Amstel) and
Neurology (Dr Wokke), University Medical Center Utrecht, Utrecht; the
Department of Neurology, Leiden University Medical Center, Leiden (Dr
van Hilten); and the Departments of Human Genetics (Dr Knoers) and
Neurology (Dr Kremer), University Medical Center Nijmegen, Nijmegen,
the Netherlands.
Corresponding author: R. J. Sinke, Department of Medical Genetics,
University Medical Center Utrecht, KC04.084.2, PO Box 85090, 3508 AB
Utrecht, the Netherlands (e-mail: R.J.Sinke{at}dmg.azu.nl).
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