Objective: To present comprehensive clinical, optical coherence tomography (OCT) and genetic findings on SPG7 –related cohort attending the National Ataxia Clinic in Ireland.

Background: Hereditary cerebellar ataxias and spastic paraplegias are heterogeneous and often overlapping disorders. Mutations in SPG7 were initially linked to recessive hereditary spastic paraplegia, but more recently were identified as a common cause of recessive cerebellar ataxia. Despite extensive testing using traditional methods, a number of patients attending the National Ataxia clinic with spastic ataxia remained genetically undefined.

Methods: Next generation sequencing with a comprehensive gene panel identified disease-causing SPG7 mutations in 10 patients (9 male) with undiagnosed recessive appearing and sporadic ataxia. Other acquired and inherited causes of ataxia were excluded. 

Results: Eight patients had late onset spastic ataxia. All patients presented with ataxia or gait disturbance. One patient had no pyramidal signs. Ocular findings were present in five patients and one had external ophthalmoplegia. Eight patients had brain MRI. All underwent OCT testing. 

Gene panel testing identified SPG7 disease causing mutations in all patients. Similarly to other countries, the p.Ala510Val variant was the most common in our cohort, present in 70% on at least one allele. In addition, a patient not included in this study was found to have the same variant on one allele and another SPG7 variant of uncertain pathogenicity on the other allele. 

Conclusions: Our findings support previous data that SPG7 mutations are a more common cause of spastic ataxia than other rare recessive genes, prompting debate for change in previous assumptions about the prevalence of SPG7-related spastic ataxia. Advances in genetic testing have significantly improved the rate of positive results in patients suspected to have inherited ataxia. Deep phenotyping in a specialist clinic is crucial for clinical recognition of this syndrome and interpretation of increasingly complex genetic testing.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/spg7-related-ataxia-in-the-irish-national-ataxia-clinic-cohort-case-series/