Here we aim to provide an overview on the most frequent diseases and molecular causes underlying ataxia-parkinsonism, focusing both on novel aspects of well-known causes of ataxia-parkinsonism (MSA-C, PSP-C, FXTAS, repeat-expansion spinocerebellar ataxias [SCAs], conventional mutation SCAs) as well as on more recently identified rare genetic causes of ataxia-parkinsonism (AT, POLG, SPG7).
Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected.
Mutations in the m-AAA subunits AFG3L2 and paraplegin are associated with autosomal dominant spinocerebellar ataxia (SCA28) and autosomal recessive hereditary spastic paraplegia (SPG7), respectively.
Clinical comparisons showed that ataxias due to channelopathies had a significantly earlier age at onset with an average of 24.6 years, versus 40.9 years for polyglutamine expansion spinocerebellar ataxias and 37.8 years for SPG7-related forms (P = 0.001).