Catalog Home Page

Severe Neuropathic Pain Syndrome, with Ulceromutilating Neuropathy and Spastic Paraparesis, Associated with the p.Ala354Pro Variant in ATL1

Khade, N., Ashton, C., Davis, M., Knezevic, W and Needham, M. (2016) Severe Neuropathic Pain Syndrome, with Ulceromutilating Neuropathy and Spastic Paraparesis, Associated with the p.Ala354Pro Variant in ATL1. Neurology, 86 (16).

Abstract

Objective: To describe a family with a newly found ATL1 genetic variant and the associated phenotype. Background: Mutations in the ATL1 gene are known to cause pure early onset autosomal dominant hereditary spastic paraplegia (SPG3A) and ulceromutilating sensory neuropathy, like HSN-1. We describe the detailed clinical and electrophysiological findings in the first family with ulceromutilating sensory neuropathy, along with spastic paraparesis, carrying the p.Ala354Pro likely pathogenic variant in ATL1. Methods: Detailed clinical and electrophysiological studies were performed in affected and at risk family members. Motor and sensory conduction studies, were carried out on upper and lower limbs. Genetic analysis was carried out using a custom designed neurogenetic gene capture panel followed by massively parallel sequencing (MPS). Results: Two affected family members were investigated, as well as one unaffected. Through the family history, 12 patients were found to have had the same phenotype, including three deceased family members. One affected family member was analysed by MPS, with the p.Ala354Pro likely pathogenic variant in ATL1 being the only significant finding. The second affected family member also carried the variant, while the unaffected family member did not. The affected family members had characteristic history of a profound neuropathic pain syndrome, despite relative preservation of superficial sensory modalities. The patients also exhibited spastic paraparesis with hyper-reflexia. This resulted in recurrent painless foot ulcers and osteomyelitis. Nerve Conduction Studies (NCS) showed only a mild sensory neuropathy. Conclusions: This novel ATL1 variant potentially expands the SPG3A phenotype. The combination of severe ulceromutilating neuropathy, a profound neuropathic pain syndrome, and only mild sensory neuropathy on NCS, along with spastic paraparesis, should prompt the screening for ATL1 mutations.

Publication Type: Journal Article
Publisher: American Academy of Neurology
Copyright: © 2016 by AAN Enterprises, Inc.
URI: http://researchrepository.murdoch.edu.au/id/eprint/38441
Item Control Page Item Control Page