Objective: To identify the prevalence and phenotype of patients with biallelic pathogenic SPG7 mutations

Background: Spastic Paraplegia Type 7 (SPG7) is an autosomal recessive disorder historically presenting as a Hereditary Spastic Paraparesis (HSP).  It is now widely known that the phenotype of SPG7 is broad, including a pure cerebellar ataxia, mixed spastic-ataxia, and additional neurological manifestations including sensorimotor neuropathy and optic atrophy.

Method: An audit of patients with confirmed biallelic pathogenic mutations on the SPG7 gene was undertaken at The Walton Centre.

Results: Overall, twenty patients were identified, eight of whom had a ‘pure’ HSP phenotype. Eight had a complex phenotype with mixed spastic-ataxia and three had a pure cerebellar ataxia without evidence of spasticity. One patient had a novel phenotype of chronic progressive external ophthalmalgia without any additional neurological features. average age of symptom onset was 49 years old. Seven patients had a genetically confirmed relative with SPG7 including a sibling trio.

MRI brain imaging was available fifteen patients, with significant cerebellar volume loss present in 67% of scans. The ‘eye of the tiger sign’ has previously been reported in some patients with SPG7 but was not present in any of our cohort. 80% of scans had evidence of dentate hyperintensity on T2 weighted imaging.

The most prevalent pathogenic variant was that of c.1529C>T, p(Ala510Val) which is in keeping with other cohort studies. Five of our patients were homozygous for this variant with a further nine patients compound heterozygous for this variant. We did not identify any significant differences in presentation between compound heterozygotes of homozygotes of the c.1529C>T, p(Ala510Val) allele.

Conclusion: Our findings suggest that SPG7 is perhaps more prevalent that current estimates with a wider phenotypic spectrum. Additionally, our findings support dentate nucleus T2 hyperintensity as a radiological sign in SPG7.

References: Baviera-Muñoz R, Campins-Romeu M, Carretero-Vilarroig Let al. Clinical and genetic characteristics of 21 Spanish patients with biallelic pathogenic SPG7 mutations. J Neurol Sci. 2021 Oct 15;429:118062.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-genetic-characteristics-of-a-cohort-of-20-patients-with-confirmed-biallelic-pathogenic-spg7-mutations-from-the-north-west-of-england/