PO092 Ddhd2-associated autosomal recessive spastic ataxia in an irish family

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Abstract

Autosomal recessive cerebellar ataxias (ARCA) and hereditary spastic paraplegias (ARHSP) are rare, often overlapping, heterogeneous neurological disorders. Recently, mutations in DDHD2 have been identified as a cause of HSP (SPG54) with thin corpus callosum (TCC). We describe a large non-consanguineous Irish family with three affected siblings. All developed teenage onset, slowly progressive cerebellar ataxia with lower limb spasticity, oculomotor apraxia, intellectual disability and colour blindness. In addition, two of them had pes cavus and one had neuropathy. Other features present variably were seizures, dystonia, dysphagia and distal wasting. All affected siblings demonstrated cognitive impairment across a range of measures, with the most pronounced findings in executive function. Brain MRI, performed in two of them, showed TCC and mild cerebellar atrophy. Two siblings were found to have heterozygous expansions on chromosome 9, but no point mutation on the other allele and one had a heterozygous SPG11 variant. Genetic analysis with a targeted gene panel demonstrated novel homozygous DDHD2 mutations. This report provides comprehensive clinical and cognitive data on the associated phenotype, expanding the knowledge of this rare syndrome with communication of previously unreported phenotypic features. Better access to gene panel testing will improve the rate of genetic diagnosis in ‘non-Friedreich’s’ ARCA.

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