Dataset Information

Clinical and neuroradiological features of spinocerebellar ataxia 38 (SCA38).

ABSTRACT: SCA38 (MIM 611805) caused by mutations within the ELOVL5 gene, which encodes an enzyme involved in the synthesis of long-chain fatty acids with a high and specific expression in Purkinje cells, has recently been identified.The present study was aimed at describing the clinical and neuroimaging features, and the natural history of SCA38.We extended our clinical and brain neuroimaging data on SCA38 including 21 cases from three Italian families. All had the ELOVL5 c.689G > T (p.Gly230Val) missense mutation.Age at disease onset was in the fourth decade of life. The presenting features were nystagmus (100% of cases) and slowly progressive gait ataxia (95%). Frequent signs and symptoms included pes cavus (82%) and hyposmia (76%); rarer symptoms were hearing loss (33%) and anxiety disorder (33%). The disease progressed with cerebellar symptoms such as limb ataxia, dysarthria, dysphagia, and ophtalmoparesis followed in the later stages by ophtalmoplegia. Peripheral nervous system involvement was present in the last phase of disease with sensory loss. Dementia or extrapyramidal signs were not detected. Significant loss of abilities of daily living was reported only after 20 years of the disease. Brain imaging documented cerebellar atrophy with sparing of cerebral cortex and no white matter disease.SCA38 is a rare form of inherited ataxia with characteristic clinical features, including pes cavus and hyposmia, that may guide genetic screening and prompt diagnosis in light of possible future therapeutic interventions.

SUBMITTER: Borroni B

PROVIDER: S-EPMC4925464 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Clinical and neuroradiological features of spinocerebellar ataxia 38 (SCA38).

Borroni Barbara B Di Gregorio Eleonora E Orsi Laura L Vaula Giovanna G Costanzi Chiara C Tempia Filippo F Mitro Nico N Caruso Donatella D Manes Marta M Pinessi Lorenzo L Padovani Alessandro A Brusco Alfredo A Boccone Loredana L

Parkinsonism & related disorders 20160427

<h4>Introduction</h4>SCA38 (MIM 611805) caused by mutations within the ELOVL5 gene, which encodes an enzyme involved in the synthesis of long-chain fatty acids with a high and specific expression in Purkinje cells, has recently been identified.<h4>Objective</h4>The present study was aimed at describing the clinical and neuroimaging features, and the natural history of SCA38.<h4>Methods</h4>We extended our clinical and brain neuroimaging data on SCA38 including 21 cases from three Italian familie ...[more]

PMID: 27143115

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Project description:Spinocerebellar ataxia 36 has been recently described in Japanese families as a new type of spinocerebellar ataxia with motor neuron signs. It is caused by a GGCCTG repeat expansion in intron 1 of NOP56. Family interview and document research allowed us to reconstruct two extensive, multigenerational kindreds stemming from the same village (Costa da Morte in Galicia, Spain), in the 17th century. We found the presence of the spinocerebellar ataxia 36 mutation co-segregating with disease in these families in whom we had previously identified an ~0.8 Mb linkage region to chromosome 20 p. Subsequent screening revealed the NOP56 expansion in eight additional Galician ataxia kindreds. While normal alleles contain 5-14 hexanucleotide repeats, expanded alleles range from ~650 to 2500 repeats, within a shared haplotype. Further expansion of repeat size was frequent, especially upon paternal transmission, while instances of allele contraction were observed in maternal transmissions. We found a total of 63 individuals carrying the mutation, 44 of whom were confirmed to be clinically affected; over 400 people are at risk. We describe here the detailed clinical picture, consisting of a late-onset, slowly progressive cerebellar syndrome with variable eye movement abnormalities and sensorineural hearing loss. There were signs of denervation in the tongue, as well as mild pyramidal signs, but otherwise no signs of classical amyotrophic lateral sclerosis. Magnetic resonance imaging findings were consistent with the clinical course, showing atrophy of the cerebellar vermis in initial stages, later evolving to a pattern of olivo-ponto-cerebellar atrophy. We estimated the origin of the founder mutation in Galicia to have occurred ~1275 years ago. Out of 160 Galician families with spinocerebellar ataxia, 10 (6.3%) were found to have spinocerebellar ataxia 36, while 15 (9.4%) showed other of the routinely tested dominant spinocerebellar ataxia types. Spinocerebellar ataxia 36 is thus, so far, the most frequent dominant spinocerebellar ataxia in this region, which may have implications for American countries associated with traditional Spanish emigration.

Dataset Information

Clinical and neuroradiological features of spinocerebellar ataxia 38 (SCA38).

Publications

Clinical and neuroradiological features of spinocerebellar ataxia 38 (SCA38).

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