Spinocerebellar ataxias

Abstract

There are over 40 autosomal dominant spinocerebellar ataxias (SCAs) now identified. In this chapter we delineate the phenotypes of SCAs 1-44 and dentatorubral-pallidoluysian atrophy (DRPLA) and highlight the clinical and genetic features of the well characterised SCAs in detail in the main section of the chapter, along with their frequency and age at onset. We have included a section on the key phenotypic features of rare spinocerebellar ataxias and discuss rare and unusual presentations and genetic mechanisms of the ataxias and show differences between adult and paediatric presentations. We look at unusual mechanisms where knowledge is evolving in some dominant ataxias. For ease of reference we have tabulated historical aspects of the ataxias, major neurological diagnostic features, ataxias with predominant paediatric and infantile onset and list recognisable nerve conduction features. We comment on the anti-sense ataxia gene mechanisms and we discuss potential developments including exome sequencing and potential therapeutic options. A gene table listing all of the identified SCAs and DRPLA is also included with key references and gene locations and symbols with OMIM reference numbers for further reading.

Hereditary spastic paraplegia: from diagnosis to emerging therapeutic approaches

“…They may not be comprehensively covered by some next-generation sequencing panels and include the spinocerebellar ataxias, autosomal recessive ataxias, spastic ataxias, demyelinating and hypomyelinating leukodystrophies, and other rare metabolic and neurodegenerative disorders (table 2). [46][47][48][49][50][51][52][53] Several of the diseases in these groups, such as SCA1 (ATXN1), SCA3 (ATXN3), and Friedreich's ataxia (FXN) are triplet repeat disorders and may not therefore be covered by gene panels, even if they are extended to include wider groups of monogenic diseases associated with spasticity. [54][55][56] Particular attention should however be given to atypical presentations of treatable diseases in which lower limb spasticity occurs, often in the context of other clinical features, in the absence of T2-weighted imaging abnormalities in the spinal cord.…”

Infantile Onset of Spinocerebellar Ataxia Type 5 (SCA-5) in a 6 Month Old with Ataxic Cerebral Palsy

“…Spinocerebellar ataxia type 5 (SCA5) is characterized by a slowly progressive ataxia mainly affecting the cerebellum [1]. The mean age at onset is 33 years and is predominantly an adult onset ataxia.…”

Movement Disorders in Genetic Pediatric Ataxias

“…Yet, infantile and childhood onset has been described in many spinocerebellar ataxias, including SCA2, SCA7, SCA10, SCA13, SCA14, SCA21, SCA25, SCA28, SCA29, SCA42, SCA44, and dentatorubral-pallidoluysian atrophy. 68,69 Some cases can be explained by the phenomenon of anticipation, with earlier onset and more severe presentation in subsequent generations that is typical of expansion-repeat disorders. 68 In the uncommon situation of autosomal dominant ataxia presenting in childhood, the phenotype tends to be more severe and complex than pure ataxia.…”