Objective: To describe the phenotype and genotype of patients with confirmed diagnosis of SPG7

Background: Coarelli et al described the possible correlation between genotype and phenotype in a European cohort of patients with SPG7, they associated spasticity-predominant phenotypes with loss of function (LOF) variants, while the phenotype of cerebellar ataxia and later onset, was observed more frequent in carrier patients of at least one Ala510Val variant.

Method: We seleccted patients with confirmed diagnosis of SPG7 assesed in our unit. We analyzed clinical, radiological, and molecular variables, to performed a detail phenotype and genotype description

Results: We recruited 8 cases from 8 families. Mean age of onset 37.38 ± 10.52 y. One case with positive family history sugestive of reccesive inheritance pattern, and consangunity history in other 2 cases. Mean years of disease duration 18.13 ± 8.3 y. Predominat symptom at onset was cerebellar ataxia in 5 cases. Mean SARA score of 10,56 ± 4,9. Other associated symtopms: axonal polineuropathy (n=3), dystonia (n=2), ophtalmoparesis (n=1), and deafness (n=1). All cases presented cerebellar atrophy on brain MRI. Regarding to genotype: compound heterozygosity in 4 cases (87.5%), finding 2 missense variants, or one missense and one LOF mutation. Homozygosity in 3 cases (62.5%) (p.Ala510Val, p.Ala572Val y p.Leu78Ter). We have found only one heterozygous nonsense mutation (p.Gly352Argfs*44) in one case, after rule out a second mutation with different thecniques. Those cases with al least one p.Ala510Val mutation presented a predominant cerebellar phenotype. Only 2 cases presented a clear predominant spastic phenotype, one with homozygous missense p.Ala572Val mutation, and other with compound heterozygosity, combinding LOF and missense mutations, in this case we did not find cerebellrar signs on examination.

Conclusion: SPG7 is the paradigm of the spastic-ataxia clinical spectrum, observing that in our series the predominant phenotype is in fact the cerebellar, finding similar results to previously discribed. Therefore, the study of SPG7 gene in patients with progressive cerebellar symptoms, with or without spasticity, is esential.

References: Coarelli G, Schule R, van de Warrenburg BPC, De Jonghe P, Ewenczyk C, Martinuzzi A, Synofzik M, Hamer EG, Baets J, Anheim M, Schöls L, Deconinck T, Masrori P, Fontaine B, Klockgether T, D’Angelo MG, Monin ML, De Bleecker J, Migeotte I, Charles P, Bassi MT, Klopstock T, Mochel F, Ollagnon-Roman E, D’Hooghe M, Kamm C, Kurzwelly D, Papin M, Davoine CS, Banneau G, Tezenas du Montcel S, Seilhean D, Brice A, Duyckaerts C, Stevanin G, Durr A. Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with SPG7. Neurology. 2019 Jun 4;92(23):e2679-e2690. doi: 10.1212/WNL.0000000000007606. Epub 2019 May 8. PMID: 31068484; PMCID: PMC6556095.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/phenotype-genotype-correlation-in-a-case-series-from-south-spain-of-hereditary-spastic-paraplegia-7-spg7/