[Clinico-genetic study of type I spinocerebelllar ataxia].
Inherited, autosomal-dominant cerebellar ataxia (ADCA) comprises a genetically and clinically heterogenous group of neurodegenerative disorders. Clinical classification of these disorders was an important step [2] in differentiation among several types, the most common one being ADCA-I, accompanied with supranuclear ophthalmoplegia, optic nerve atrophy, symptoms of the basal ganglia lesions, dementia and amyotrophia. Molecular-genetic studies indicated genetic heterogeneity of ADCA-I with mutations of genetic loci on chromosome 6p (spinocerebellar ataxia type 1; SCA1), 12q (SCA2), 14q (SCA3), 19p (SCA6) and 16q (SCA4) [3]. Spinocerebellar ataxia type 1 (SCA1) is characterized by cerebellar ataxia, ophthalmoplegia and pyramidal signs [4], but also with other neurological findings that tend to prevent clinical differentiation among patients with SCA1, SCA2 and SCA3. The mutation inducing SCA1 is an instable expansion of trinucleotide (CAG) repeats in the coding region on chromosome 6 [5]. Herein, we report clinical features in patients from two families with SCA1: family I with 15 and family II with 8 affected members in 4 consecutive generations. The acceptable data (history, examination and/or insight into medical records) were obtained for 9 patients in family I and 7 patients in family II. The age at the onset of the disease was 37.8 +/- 11.3 years (mean value +/- SD) (range: 27-60) for all the patients, or 31.8 +/- 10.7 years (range: 7-60) for family I and 45.0 +/- 8.4 years (range: 35-55) for family II. Duration of the disease was 8.9 +/- 4.6 years (range: 3-15); 10.8 +/- 4.1 (range 5-15) and 5.7 +/- 3.8 years (range: 3-10) for families I and II, respectively. The mean number of CAG repeats in the mutated allele for SCA1 of the affected individuals was 50.5 +/- 6.2 (range 45-64). A significant inverse correlation (p < 0.05) was noted between the number of CAG repeats and the age at the onset of the disease (Figure 3). Similarity of initial symptoms in SCA1 was noted. They include simultaneous gait-related problems and dysarthria (usually slurred speech). Occurrence of other neurological signs (Table 3) was also predictable in most cases and depended on the phase of SCA1 at the time of examination. Generally, it is believed that intra- and interfamilial phenotypic heterogeneity in SCA1 is lower than in SCA2 and SCA3 [12]). In conclusion, typical clinical manifestations of SCA1, at least in early phases of the disease, according to our study, include gait ataxia, dysarthria, brisk muscle reflexes and marked hand ataxia; the age at the onset of the disease was inverse, and clinical progression was directly related to the number of CAG repeats in the mutated allele on chromosome 6. Nevertheless, significant differences in clinical properties of this inherited disease are possible among different affected families.
Svetel
M
M
Institute of Neurology, Clinical Centre of Serbia, Belgrade.
Culjković
B
B
Sternić
N
N
Dragasević
B
B
Stojković
I
I
Romac
S
S
Kostić
V S
VS
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D013132:Spinocerebellar Degenerations / Q000175:diagnosis / Q000235:genetics*; D018911:Trinucleotide Repeats