X-linked ataxias

Abstract

X-linked cerebellar ataxias (XLCA) are an expanding group of genetically heterogeneous and clinically variable conditions characterized by cerebellar dysgenesis (hypoplasia, atrophy, or dysplasia) caused by gene mutations or genomic imbalances on the X chromosome. The neurologic features of XLCA include hypotonia, developmental delay, intellectual disability, ataxia, and other cerebellar signs. Normal cognitive development has also been reported. Cerebellar defects may be isolated or associated with other brain malformations or extraneurologic involvement. More than 20 genes on the X chromosome, mainly encoding for proteins involved in brain development and synaptic function that have been constantly or occasionally associated with a pathologic cerebellar phenotype, and several families with X-linked inheritance have been reported. Given the excess of males with ataxia, this group of conditions is probably underestimated and families of patients with neuroradiologic and clinical evidence of a cerebellar disorder should be counseled for high risk of X-linked inheritance.

Keywords: X-chromosome (or X-linked); ataxia; cerebellar atrophy; cerebellar hypoplasia; intellectual disabililty.