References for this review were identified by searches of PubMed from 1966 until June 2006 with the terms “cerebellar ataxia”, “recessive cerebellar ataxia”, “Friedreich ataxia”, “AVED”, “abetalipoproteinemia”, “Refsum disease”, “late onset Tay-Sachs”, “cerebrotendinous xanthomatosis”, “POLG ataxia”, “SCAN1”, “ataxia telangiectasia”, “AOA1”, “AOA2”, “ARSACS”, “IOSCA”, “Cayman ataxia”, and “Marinesco-Sjogren”. Due to space limitations, emphasis was placed on comprehensive reviews and
ReviewClinical features and molecular genetics of autosomal recessive cerebellar ataxias
Section snippets
Clinical features of autosomal recessive ataxias
Insidious loss of balance and coordination can be debilitating for patients and a diagnostic dilemma for clinicians. The phenotype of progressive cerebellar ataxia can result from both acquired and hereditary disorders. For these reasons, a systematic approach to the diagnosis of patients with ataxia is essential. Hereditary ataxias can be divided into autosomal dominant, autosomal recessive, X-linked, and mitochondrial on the basis of mode of inheritance. This Review will focus on the clinical
Friedreich's ataxia and phenotypically related disorders
Friedreich's ataxia is an important consideration in all assessments of autosomal recessive ataxic syndromes. However, several other ataxic disorders strongly mimic this phenotype. Therefore, the initial characterisation of a patient as having Friedreich's ataxia phenotype is a useful first step in differentiation. Despite their clinical similarity, these disorders are easily differentiated by laboratory testing and, ultimately, through genetic analysis.
Friedreich's ataxia phenotype with cerebellar atrophy
As with the disorders described above, the following disorders can mimic the Friedreich's ataxia phenotype; however, they can be readily distinguished by the presence of cerebellar atrophy or other findings on neuroimaging. Furthermore, the presence of clinical neurological findings not typically seen in Friedreich's ataxia, such as epilepsy or cognitive or psychiatric symptoms, should also alert physicians to consider these disorders in the differential diagnosis.
Early-onset ataxia with cerebellar atrophy
This final class of disorders differs from those previous in that the age at onset is typically much younger than seen in Friedreich's ataxia and phenotypically similar disorders. Cerebellar atrophy is also a prominent feature. Ataxia telangiectasia is the prototypical disorder in this group. Although they may present in the teenage years, ataxia with oculomotor apraxia types 1 and 2 are also included in this category due to their notable similarities to ataxia telangiectasia. This category is
Conclusion
Among the hereditary ataxias, those with autosomal recessive inheritance form a heterogeneous population. The major disorders can be effectively grouped into three categories. The first two of these are best represented clinically by Friedreich's ataxia, while the last category is exemplified by ataxia telangiectasia. Although additional clinical assessment can aid in further differentiation within these categories (table 2), ancillary testing with simple laboratory studies and neuroimaging can
Search strategy and selection criteria
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