Objective: To present the clinical profiles of two siblings with SCA11 who are of Hispanic origin.

Background: Spinocerebellar ataxia type 11 (SCA11) is an autosomal dominant ataxia whose prevalence is unknown but is rare.  SCA11 is characterized by progressive cerebellar ataxia and abnormal eye movements. Pyramidal features, peripheral neuropathy, and dystonia may also be seen. Only four families have been previously reported to date with a mean age of onset of 24.2 ± 8.4 years, range 15– 43.

Methods: The patients are two brothers originally from Puerto Rico.  Patient 1, now age 48, developed loss of balance when walking when he was 24, and this has gradually worsened over time.  On exam, he has course saccades in horizontal and vertical directions, moderate dysarthric slurred speech, dysmetria on finger-to-nose and heel-to-shin, bilateral dysdiadochokinesia, and wide-based ataxic gait with inability to tandem.  Patient 2, now aged 55, developed balance problems when he was 22.  He has similar but more severe symptoms, in that he has horizontal nystagmus looking to left, right and vertical, dysmetria with finger-to-nose and heel-to-shin, bilateral dysdiadochokinesia, decreased sensation in all modalities below the calves, and a waddling gait.  

Results: MRI brain for both patients showed marked cerebellar atrophy without brainstem or upper cervical cord abnormality. Both patients showed mutations in the TTBK2 gene with frameshift mutation (c.1306_1307 2 bp del GA; codon:436) consistent with a diagnosis of SCA11.

Conclusions: SCA11 is caused solely by mutation of TTBK2.  Only four family cases from Germany, French, Pakistan, and England have been reported to have SCA11. All four cases had similar single heterozygous truncated TTBK2 (i.e.,TTBK2truncated/+) caused by a premature stop codon and termination at residues 448 (frameshift deletions at codons 435), 448 (frameshift deletions at codons 435), 449 (frameshift deletions at codons 428/429), and 450 (one base insertion at codon 444), respectively.  Our cases are unique in that this is the first time that a family of Hispanic origin has been described at a novel codon, 436, for frameshift deletion.  SCA11-linked mutations of TTBK2 have been show to dramatically reduce the kinase activity to 10% of full- length TTBK2 and promote their nuclear localization.  The effect of TTBK2 nuclear localization on neurotoxicity is unknown.  Thus, the precise disease mechanism linking TTBK2 mutation and SCA11 remains unclear.

References:  

Bauer P et al. Spinocerebellar ataxia type 11 (SCA11) is an uncommon cause of dominant ataxia among French and German kindreds.  J Neurol Neurosurg Psychiatry 2010;81:1229e1232

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MDS Abstracts - https://www.mdsabstracts.org/abstract/spinocerebellar-ataxia-type-11-in-a-hispanic-kindred/