Autosomal Dominant Cerebellar Ataxia Type Research Articles

Deciphering the natural history of SCA7 in children.

Childhood-onset autosomal dominant cerebellar ataxia type 7 (SCA7) is a severe disease which leads to premature loss of ambulation and death. Early diagnosis of SCA7 is of major importance for genetic counselling and still relies on specific genetic testing, driven by clinical expertise. However, the precise phenotype and natural history of paediatric SCA7 has not yet been fully described. Our aims were to describe the natural history of SCA7 in a large multicentric series of children of all ages, and to find correlates to variables defining this natural history. We collected and analysed clinical data from 28 children with proven SCA7. All had clinical manifestations of SCA7 and either a definite number of CAG repeats in ATXN7 or a long expansion>100 CAG. We identified four clinical presentation patterns related to age at onset. Children of all age groups had cerebellar atrophy and retinal dystrophy. Our data, combined with those in the literature, suggest that definite ranges of CAG repeats determine paediatric SCA7 subtypes. The number of CAG repeats inversely correlated to all variables of the natural history. Age at gait ataxia onset correlated accurately to age at loss of walking ability and to age at death. SCA7 in children has four presentation patterns that are roughly correlated to the number of CAG repeats. Our depiction of the natural history of SCA7 in children may help in monitoring the effect of future therapeutic trials.

Infantile Onset Spinocerebellar Ataxia 2 (SCA2)

Autosomal dominant cerebellar ataxia type I is a heterogeneous group of spinocerebellar ataxias with variable neurologic presentations, with age of onset varying from infancy to adulthood. Autosomal dominant cerebellar ataxia type I is composed mainly of 3 prevalent spinocerebellar ataxia types with different pathogenic loci, specifically spinocerebellar ataxia 1 (6p24-p23), spinocerebellar ataxia 2 (12q24.1), and spinocerebellar ataxia 3 (14q32.1). The shared pathogenic mutational event is the expansion of the CAG repeat that results in polyglutamine extended stretches in the encoded proteins. CAG repeat disorders generally show the phenomenon of anticipation, which is more often associated with paternal transmission. In this report, we describe a patient with infantile-onset spinocerebellar ataxia type 2 (~320 CAG repeat) who inherited the disease from his father (47 CAG repeats). We have summarized the clinical, neuroimaging, electroencephalographic (EEG), and molecular data of previous cases and attempt to highlight the most consistent findings. Our intent is to help treating clinicians to suspect this disorder and to offer timely genetic counseling for a currently potentially untreatable disorder.

Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics

Autosomal Dominant Cerebellar Ataxia (ADCA) Type III is a type of spinocerebellar ataxia (SCA) classically characterized by pure cerebellar ataxia and occasionally by non-cerebellar signs such as pyramidal signs, ophthalmoplegia, and tremor. The onset of symptoms typically occurs in adulthood; however, a minority of patients develop clinical features in adolescence. The incidence of ADCA Type III is unknown. ADCA Type III consists of six subtypes, SCA5, SCA6, SCA11, SCA26, SCA30, and SCA31. The subtype SCA6 is the most common. These subtypes are associated with four causative genes and two loci. The severity of symptoms and age of onset can vary between each SCA subtype and even between families with the same subtype. SCA5 and SCA11 are caused by specific gene mutations such as missense, inframe deletions, and frameshift insertions or deletions. SCA6 is caused by trinucleotide CAG repeat expansions encoding large uninterrupted glutamine tracts. SCA31 is caused by repeat expansions that fall outside of the protein-coding region of the disease gene. Currently, there are no specific gene mutations associated with SCA26 or SCA30, though there is a confirmed locus for each subtype. This disease is mainly diagnosed via genetic testing; however, differential diagnoses include pure cerebellar ataxia and non-cerebellar features in addition to ataxia. Although not fatal, ADCA Type III may cause dysphagia and falls, which reduce the quality of life of the patients and may in turn shorten the lifespan. The therapy for ADCA Type III is supportive and includes occupational and speech modalities. There is no cure for ADCA Type III, but a number of recent studies have highlighted novel therapies, which bring hope for future curative treatments.

Autosomal dominant cerebellar ataxia type I: A review of the phenotypic and genotypic characteristics

Type I autosomal dominant cerebellar ataxia (ADCA) is a type of spinocerebellar ataxia (SCA) characterized by ataxia with other neurological signs, including oculomotor disturbances, cognitive deficits, pyramidal and extrapyramidal dysfunction, bulbar, spinal and peripheral nervous system involvement. The global prevalence of this disease is not known. The most common type I ADCA is SCA3 followed by SCA2, SCA1, and SCA8, in descending order. Founder effects no doubt contribute to the variable prevalence between populations. Onset is usually in adulthood but cases of presentation in childhood have been reported. Clinical features vary depending on the SCA subtype but by definition include ataxia associated with other neurological manifestations. The clinical spectrum ranges from pure cerebellar signs to constellations including spinal cord and peripheral nerve disease, cognitive impairment, cerebellar or supranuclear ophthalmologic signs, psychiatric problems, and seizures. Cerebellar ataxia can affect virtually any body part causing movement abnormalities. Gait, truncal, and limb ataxia are often the most obvious cerebellar findings though nystagmus, saccadic abnormalities, and dysarthria are usually associated. To date, 21 subtypes have been identified: SCA1-SCA4, SCA8, SCA10, SCA12-SCA14, SCA15/16, SCA17-SCA23, SCA25, SCA27, SCA28 and dentatorubral pallidoluysian atrophy (DRPLA). Type I ADCA can be further divided based on the proposed pathogenetic mechanism into 3 subclasses: subclass 1 includes type I ADCA caused by CAG repeat expansions such as SCA1-SCA3, SCA17, and DRPLA, subclass 2 includes trinucleotide repeat expansions that fall outside of the protein-coding regions of the disease gene including SCA8, SCA10 and SCA12. Subclass 3 contains disorders caused by specific gene deletions, missense mutation, and nonsense mutation and includes SCA13, SCA14, SCA15/16, SCA27 and SCA28. Diagnosis is based on clinical history, physical examination, genetic molecular testing, and exclusion of other diseases. Differential diagnosis is broad and includes secondary ataxias caused by drug or toxic effects, nutritional deficiencies, endocrinopathies, infections and post-infection states, structural abnormalities, paraneoplastic conditions and certain neurodegenerative disorders. Given the autosomal dominant pattern of inheritance, genetic counseling is essential and best performed in specialized genetic clinics. There are currently no known effective treatments to modify disease progression. Care is therefore supportive. Occupational and physical therapy for gait dysfunction and speech therapy for dysarthria is essential. Prognosis is variable depending on the type of ADCA and even among kindreds.

Identification of five spinocerebellar ataxia type 2 pedigrees in patients with autosomal dominant cerebellar ataxia in Taiwan.

The autosomal dominant cerebellar ataxias (ADCAs) are a group of genetically diverse neurological conditions linked by progressive deterioration in balance and coordination. Spinocerebellar Ataxia Type 2 (SCA2) is one of the ADCAs and also belongs to a special group caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. We aimed to investigate the frequency of SCA2 mutation in the ataxia patients referred to the clinic. We screened 58 families with inherent cerebellar ataxia and 57 normal individuals by the use of radioactive genomic polymerase chain reaction (PCR) method. A simple non-radioactive PCR for rapid detection of the expanded SCA2 alleles via agarose gel electrophoresis was also employed. Eight SCA2 affected patients and 1 at-risk individual in 5 unrelated SCA2 families were identified. The CAG repeats of normal alleles in the sample studied range in size from 16 to 30 repeat units, while those of SCA2 chromosomes are expanded to 34 to 49 repeat units. Our results also showed that unlike SCA 1 and SCA3/MJD, the size distribution of the normal alleles showed few polymorphisms, with the 22 repeat allele accounting for 90.1%. Homozygosity in normal individuals was 80.2%. No overlap in ataxin-2 allele size between normal and expanded chromosomes was observed. This is the first report of the SCA2 gene distributions in the population of Taiwan. The SCA2 mutation accounts for 8.6% of ADCA type I families referred to us, intermediate between SCA1(1.7%) and SCA3/MJD (24%) of the ADCA type I families in our collection.

Clinical and genetic analysis of spinocerebellar ataxia type 11

The autosomal dominant cerebellar ataxias (ADCAs) are a genetically heterogeneous group of disorders. Clinical classification of the ADCAs into three types has facilitated defining phenotypes and in turn, linkage analysis, which has led to the discovery of 30 loci and 16 genes. The type III ADCAs are 'pure' spinocerebellar ataxias (SCA), those that appear to elude neurological features outside of the cerebellum. At present 3 ADCA type III SCA genes have been published, SCA5, SCA6, and SCA14, these three genes appear to have various roles suggesting involvement in both different and possibly overlapping neurodegenerative pathways. The known ADCAIII genes are thought to have such roles as involvement in signal transduction, cell proliferation, synaptic transmission, and channel regulation. Here we update readers on the current progress on SCA11 and the identification of the disease gene. We discuss the clinical, genetic, and pathological details of SCA11--a locus at chromosome 15q14-q21.3 in a Caucasian family of British ancestry. We also discuss the refining of this region, and methods used to prioritize the screening of the over 130 candidate genes in this genomic region.

Trace eyeblink conditioning in patients with cerebellar degeneration: comparison of short and long trace intervals

To elucidate whether the cerebellar cortex may contribute to trace eyeblink conditioning in humans, eight patients with degenerative cerebellar disorders (four with sporadic adult onset ataxia, three with autosomal dominant cerebellar ataxia type III and one with spinocerebellar ataxia type 6) and eight age- and sex-matched healthy control subjects were investigated. Individual high resolution three-dimensional MRI data sets were acquired. As revealed by volumetric measurements of the cerebellum using ECCET software, patients showed cerebellar atrophy to various degrees. No abnormalities were observed in the control subjects. Eyeblink conditioning was performed twice using a tone of 40 ms as conditioned stimulus, followed by a short (400 ms) and a long (1,000 ms) trace interval and an air-puff of 100 ms as unconditioned stimulus. Using the short trace interval, eyeblink conditioning was significantly impaired in cerebellar patients compared to controls, even in those who fulfilled criteria of awareness. Using the long trace interval no significant group differences could be observed. The present findings of impaired trace eyeblink acquisition in patients with cortical cerebellar degeneration suggest that the cerebellar cortex in humans, in addition to the interposed nucleus, is involved in trace eyeblink conditioning, if the trace interval is relatively short. Using a long trace interval, the cerebellum appears to be less important.

Degree of Cerebellar Ataxia Correlates with Three-Dimensional MRI-Based Cerebellar Volume in Pure Cerebellar Degeneration

The aim of the present study was to compare the severity of cerebellar ataxia as measured by the International Cooperative Ataxia Rating Scale (ICARS) by Trouillas et al. [ J Neurol Sci 1997;145:205–211] with the cerebellar volume in chronic cerebellar disease. Fifteen patients with pure cerebellar degeneration were investigated. Seven patients suffered from spinocerebellar ataxia type 6, 5 from idiopathic late-onset cerebellar ataxia, 2 from autosomal dominant cerebellar ataxia type III and 1 from episodic ataxia type 2. Volumetric analysis was based on individual three-dimensional MR images. Total ICARS score significantly inversely correlated with the cerebellar volume (r = –0.805, p < 0.0001), correlations between ICARS subscores and cerebellar volume were significant for upper and lower limb ataxia, ataxia of posture and gait, and dysarthria, but not for the oculomotor subscore. The results suggest that the degree of cerebellar atrophy in pure cerebellar degenerative disorders is accompanied by comparable functional impairment (i.e. degree of cerebellar ataxia).

The Lewis family revisited: No evidence for autosomal dominant multiple system atrophy

In 1964, Lewis reported a familial ataxia-dysautonomia syndrome reminiscent of Shy–Drager syndrome subsequently known as multiple system atrophy (MSA). Here we review this report and propose that the Lewis family may represent an unusual form of autosomal dominant cerebellar ataxia type I, which might be categorized either as SCA3 (Machado-Joseph disease) or a new SCA subtype. There remains no conclusive evidence to support the notion of hereditary MSA.

Spinocerebellar ataxia type 14

In this issue of Neurology , Chen et al.1 report the clinical and molecular genetic features of nine families with autosomal dominant spinocerebellar ataxia type 14 (SCA-14), which is caused by mutations in the protein kinase Cγ ( PRKCG ) gene. The autosomal dominant SCAs are a heterogeneous family of hereditary neurodegenerative disorders characterized by dysfunction and atrophy of the cerebellum and its major connections, resulting in progressive ataxia.2 Some of the SCAs are characterized by a pure cerebellar syndrome, previously called autosomal dominant cerebellar ataxia (ADCA) type III, but most cause a more widespread atrophy and consequently additional neurologic signs and symptoms, referred to as ADCA type I and type II (the latter being characterized by coexisting retinal degeneration and associated with SCA-7 mutations). So far, >25 different genetic loci have been associated with forms of autosomal dominant SCAs, but the causative mutations have been identified in less than half of these cases.2 Most SCAs of known cause are due to expansions of a CAG repeat sequence in the coding region of the respective gene, resulting in an expanded polyglutamine stretch in the encoded protein. These SCAs share the basic mutation mechanism and probably also share many aspects of their pathogenesis with other polyglutamine disorder such as …

Fine mapping of 16q-linked autosomal dominant cerebellar ataxia type III in Japanese families.

The autosomal dominant cerebellar ataxias (ADCAs) are a clinically and genetically heterogeneous group of disorders. To date, at least 11 genes and 13 additional loci have been identified in ADCAs. Despite phenotypic differences, spinocerebellar ataxia 4 (SCA4) and Japanese 16q-linked ADCA type III map to the same region of 16q22.1. We report four Japanese families with pure cerebellar ataxia and a disease locus at 16q22.1. Our families yielded a peak lod score of 6.01 at marker D16S3141. To refine the candidate region, we carried out genetic linkage studies in four pedigrees with a high density set of DNA markers from chromosome 16q22.1. Our linkage data suggest that the disease locus for 16q-ADCA type III is within the 1.25-Mb interval delineated by markers 17msm and CTTT01. We screened for mutations in 36 genes within the critical region. Our critical region lies within the linkage interval reported for SCA4 and for Japanese 16q-ADCA type III. These data suggest that the ADCA that we have characterized is allelic with SCA4 and Japanese 16q-linked ADCA type III.

Physical map and haplotype analysis of 16q-linked autosomal dominant cerebellar ataxia (ADCA) type III in Japan.

Autosomal dominant cerebellar ataxia (ADCA) is a group of heterogeneous neurodegenerative disorders. We previously mapped a gene locus for ADCA with pure cerebellar syndrome (ADCA type III) to a 3-cM region in chromosome 16q, and found a common haplotype among affected individuals. This region was exactly within the locus for another ADCA, spinocerebellar ataxia type 4 (SCA4). To identify the gene causing 16q-linked ADCA type III, we constructed a contig with 38 bacterial artificial chromosome clones between D16S3043 and D16S3095. The size of this contig was estimated to be 4.8 Mb. We found more than 500 nucleotide tandem repeats, including 9 CAG/CTG repeats in this candidate region, although none of the 94 tandem repeats analyzed were expanded in affected individuals. However, we found 11 new polymorphic markers, giving 22 markers spanning the candidate region. By typing these markers on eight Japanese families with ADCA type III, including two new families, we found that a common "founder" haplotype is seen in a more restricted 3.8-Mb region, spanning markers GGAA05 and D16S3095. We present here a newly refined critical interval of 16q-ADCA type III/SCA4. Data of 11 new DNA markers on 16q22.1 would also be useful for other research of genes mapped to this region.

¿Tienen nuestros resúmenes (abstracts) lo que deben tener? Un análisis de la década 1991-2000

The autosomal dominant cerebellar ataxias (ADCA) type I are a group of neurological disorders that are clinically and genetically heterogeneous. Two genes implicated in the disease, SCA1 (spinal cerebellar ataxia 1) and SCA2, are already localized. We have mapped a third locus to chromosome 14q24.3-qter, by linkage analysis in a non-SCA1/non-SCA2 family and have confirmed its existence in a second such family. We suggest designating this new locus "SCA3". Combined analysis of the two families restricted the SCA3 locus to a 15-cM interval between markers D14S67 and D14S81. The gene for Machado-Joseph disease (MJD), a clinically different form of ADCA type I, has been recently assigned to chromosome 14q24.3-q32. Although the SCA3 locus is within the MJD region, linkage analyses cannot yet demonstrate whether they result from mutations of the same gene. Linkage to all three loci (SCA1, SCA2, and SCA3) was excluded in another family, which indicates the existence of a fourth ADCA type I locus.

Spinocerebellar ataxias caused by polyglutamine expansions.

Autosomal dominant cerebellar ataxias (ADCA) constitute a group of disorders, clinically and molecularly heterogeneous. They are characterized by variable degrees of cerebellar and brainstem degeneration or dysfunction. Neuronal loss variably affects the pons, the inferior olive, the basal ganglia, the cerebellum and its afferent and efferent fibers. Onset is generally during the third or fourth decade but can also occur in childhood or in the old age. Patients usually present with progressive cerebellar ataxia and associated neurological signs, such as ophthalmoplegia, pyramidal or extrapyramidal signs, deep sensory loss and dementia. Attempts to classify subtypes of ADCA were largely unsatisfactory until AE Harding distinguished three phenotypes based on clinical associated signs. ADCA type I is the most common subtype and variably combines cerebellar ataxia, dysarthria, ophthalmoplegia, pyramidal and extrapyramidal signs, deep sensory loss, amyotrophy and dementia. However, several other signs and symptoms may also be associated, i.e., slow eye movements, sphincter disturbances, axonal neuropathy, fasciculation and/ or swallowing difficulties. ADCA type II was first described by Froment et al and is characterized by the association of progressive macular degeneration with cerebellar ataxia. Finally, ADCA type III denotes a “pure”, generally late onset, cerebellar syndrome.

A linkage disequilibrium at the candidate gene locus for 16q-linked autosomal dominant cerebellar ataxia type III in Japan.

We previously mapped the gene responsible for autosomal dominant cerebellar ataxia (ADCA) type III to a 10.9-cM interval between D16S3089 and D16S515 on chromosome 16q. This region, however, was identical to the candidate locus of spinocerebellar ataxia type 4 (SCA4). In this study, we extended our research to refine the gene locus of the disease by applying linkage disequilibrium with 20 microsatellite DNA markers. With 9 markers flanked by D16S3031 and D16S3107, we found that the affected individuals in six families had a common haplotype on their disease chromosomes. Furthermore, linkage disequilibrium was demonstrated with 5 informative markers: D16S3019 (P = 0.013), D16S3067 (P = 0.008), D16S3141 (P = 0.011), D16S496 (P = 0.032), and D16S3107 (P = 0.000). These results indicate that the disease could have originated from a common ancestor harboring a mutation within a less than 3-cM region between D16S3043 and D16S3095. The founder alleles were also observed in other patients with ADCA type III unrelated to the six families.

Proton magnetic resonance spectroscopic imaging reveals differences in spinocerebellar ataxia types 2 and 6

The objective of this study was to investigate cerebellar metabolism in patients with autosomal dominant cerebellar ataxia type 1 (ADCA-I) carrying two distinct mutations of spinocerebellar ataxia (SCA). Non-invasive image-guided proton magnetic resonance spectroscopy imaging (1H-MRSI) was performed in 4 patients with SCA2, and 3 patients carrying the SCA6 mutation. For MRSI, we employed a spin-echo sequence (TR = 1500 msec, TE = 135 msec, slice thickness = 15 mm, FOV = 240 mm) and a stimulated-echo sequence (TR = 1500 msec, TE = 20 msec, slice thickness = 15 mm, FOV = 240 mm). Measures included the peak integral ratios of neuronal and glial markers [N-acetylaspartate (NA) to creatine (Cr), choline-containing compounds (CHO) to Cr, and lactate (LAC) to Cr]. We found NA:Cr ratios were significantly lower in patients with SCA2 (40.4% lower) compared to patients carrying the SCA6 mutation. CHO:Cr ratios differed between the two mutations using short echo time (30.8% lower in SCA2), but not when applying long echo time 1H-MRSI. Measurements using long echo time revealed LAC peaks in all SCA2 patients. 1H-MRSI revealed metabolic differences between SCA2 and SCA6 patients. NA:Cr ratios were significantly lower in patients with the SCA2 mutation compared to the SCA6 mutation, and LAC signals were obtained in the cerebella of SCA2 patients. In addition, CHO:Cr ratios showed different behavior using short and long TE, indicating differences in relaxation times of choline compounds in SCA2.

A gene on SCA4 locus causes dominantly inherited pure cerebellar ataxia.

Several different genes or their loci have been identified for autosomal dominant cerebellar ataxia (ADCA). However, other types of ataxia remain unassigned. To identify a new locus for ADCA. Six Japanese families with ADCA with pure cerebellar syndrome (ADCA type III) were examined. These families had been molecularly excluded for spinocerebellar ataxia (SCA) types 1 through 3, 5 through 8, and 10. Clinical examination was undertaken, and a genome-wide linkage search was performed on 250 microsatellite DNA markers. Strong evidence for linkage was found with markers on human chromosome 16q, and haplotype and multipoint analyses further refined the gene locus in a 10.9-cM interval between D16S3089 and D16S515. Linkage disequilibrium was further found with the marker D16S3107 within the interval. The locus was exactly the candidate interval of SCA4, a rare form of ADCA clinically characterized by ataxia with sensory neuropathy and pyramidal tract signs. This would suggest that SCA4 and our ADCA type III are likely to be allelic disorders with different clinical features. The current study provides evidence that a gene on the SCA4 locus causes a pure cerebellar syndrome.

Molecular and clinical analyses of spinocerebellar ataxia type 8 in Japan.

To clarify the molecular and clinical features of the newly identified spinocerebellar ataxia type 8 (SCA8). We analyzed the CTG repeat region of the SCA8 gene in a series of Japanese patients with cerebellar ataxia. We also investigated the frequency of the CTG repeat length in Japanese normal elderly subjects older than age 79. Morphometric measurements on the cerebral MRI were compared between patients with SCA8 and SCA6. The number of the combined CTA/CTG repeats of six affected SCA8 alleles was 106.3+/-24.4 (mean +/- SD) ranging from 89 to 155 and that of normal elderly subjects was 24.3+/-4.4 (n = 104 alleles) ranging from 15 to 34. The mean age at onset of the SCA8 cases was 53.8+/-19.7 years, with a range from 20 to 73 years. One father and daughter from an SCA8 family showed remarkable paternal anticipation. The number increase from father to daughter was + 16 CTG repeats, with a 31-year acceleration of onset. The six identified SCA8 patients were clinically characterized by high frequencies of incoordination of trunk and limbs, ataxic dysarthria, impaired smooth pursuit, and horizontal nystagmus, and the MRI showed significant atrophy of the cerebellar vermis and hemispheres compared with that of normal controls. There was no significant difference between SCA8 and SCA6 on the morphometric MRI study. The CTG repeat expansions in the SCA8 alleles were much greater than the range of repeats in normal elderly subjects. The SCA8 phenotype manifested by cerebellar symptoms and atrophy corresponded to features of the autosomal dominant cerebellar ataxia type III (ADCA III).

Autosomal Dominant Cerebellar Ataxia Type III: Linkage in a Large British Family to a 7.6-cM Region on Chromosome 15q14-21.3

Autosomal dominant cerebellar ataxia type III (ADCA III) is a relatively benign, late-onset, slowly progressive neurological disorder characterized by an uncomplicated cerebellar syndrome. Three loci have been identified: a moderately expanded CAG trinucleotide repeat in the SCA 6 gene, the SCA 5 locus on chromosome 11, and a third locus on chromosome 22 (SCA 10). We have identified two British families in which affected individuals do not have the SCA 6 expansion and in which the disease is not linked to SCA 5 or SCA 10. Both families exhibit the typical phenotype of ADCA III. Using a genomewide searching strategy in one of these families, we have linked the disease phenotype to marker D15S1039. Construction of haplotypes has defined a 7.6-cM interval between the flanking markers D15S146 and D15S1016, thereby assigning another ADCA III locus to the proximal long-arm of chromosome 15 (SCA 11). We excluded linkage of the disease phenotype to this region in the second family. These results indicate the presence of two additional ADCA III loci and more clearly define the genetic heterogeneity of ADCA III.

Polyneuropathy in autosomal dominant cerebellar ataxias: Phenotype–genotype correlation

Autosomal dominant cerebellar ataxias (ADCAs) are clinically and genetically heterogeneous neurodegenerative disorders. The aim of this study was to evaluate electrophysiologically peripheral nervous system involvement in each of the groups studied and its correlation with the number of CAG repeats. Forty patients with ADCA were clinically and electrophysiologically investigated. Thirty-five patients belonged to the ADCA type I group (SCA1, 12; SCA2, 10; SCA3, 13) and five to the ADCA type II group. Axonal sensory or sensorimotor polyneuropathy was found in 42% of the SCA1 patients, 80% of the SCA2 patients, and 54% of the SCA3 patients, whereas electrophysiological studies were normal in all those with ADCA type II. The number of CAG repeats was significantly higher in SCA1 patients with polyneuropathy than in those without polyneuropathy (P = 0.01), whereas the reverse was observed in SCA3/MJD (Machado–Joseph disease) patients (P = 0.05). We conclude that axonal polyneuropathy is often associated with ADCA type I, but its frequency varies according to factors such as the locus responsible and the number of CAG repeats. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 712–717, 1999.