Clinical and genetic analysis of 4 Mexican families with spinocerebellar ataxia type 10

Abstract

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder caused by expansion of an unstable ATTCT repeat. SCA10 has been described as a pure cerebellar syndrome accompanied by seizures and has been recognized only in families of Mexican origin. We describe clinical and molecular findings of 18 patients in four Mexican families with SCA10. Affected individuals had an average age at onset of 26.7 years (range 14-44 years) and ATTCT repeats ranging from 920 to 4,140 repeats. We could not detect significant anticipation or correlation between repeat size and age at onset, probably due to the small sample size. In addition to pure cerebellar ataxia and seizures, patients often showed soft pyramidal signs, ocular dyskinesia, cognitive impairment, and/or behavioral disturbances. Brain magnetic resonance imaging showed predominant cerebellar atrophy, and nerve conduction studies indicated polyneuropathy in 66% of patients. One family showed hepatic, cardiac, and hematological abnormalities in affected members. These findings suggest that a wide range of tissues may be affected in SCA10, including those outside of the cerebellum and cerebral cortex.

Spinocerebellar ataxias

“…The authors did not observe any significant anticipation or any correlation between age at onset of the disease and the number of AT-TCT repeats. In addition to cerebellar ataxia and epilepsy (found in 72.2% of the cases), clinical findings included peripheral polyneuropathy in 66% of the cases (confirmed by a nerve conduction study) and cerebellar atrophy, which was predominant in MRI examinations; in some cases mild pyramidal signs, ocular dyskinesia, cognitive dysfunction and/or behavioral disorders were observed, as well as liver, heart and hematological dysfunction 31 .…”

“…It has well-defined clinical characteristics: patients present with a "pure" cerebellar syndrome, often accompanied by epilepsy and sometimes by peripheral neuropathy 16,31,32 . 8,18 .…”

“…The disease-causing mutation that leads to SCA 10 is a large expansion of a pentanucleotide (ATTCT) repeat located in an intron of a gene of unknown function (SCA 10) on chromosome 22q 16,[31][32][33][34] .…”

“…Neuroimaging studies, particularly magnetic resonance imaging of the brain, show the presence of pan-cerebellar atrophy without any abnormalities in other regions 16,31,32 .…”

The history of spinocerebellar ataxia type 10 in Brazil: travels of a gene

“…SCA type 10 was originally identifi ed only in Mexican familes and had a phenotype characterized by a combination of cerebellar ataxia and epilepsy [5][6][7][8][9] .…”