Open AccessSpastic paraplegia type 73: expanding phenotype of the first two Brazilian families
Author(s) -
Vinícius Lopes Braga,
Wladimir Bocca Vieira de Rezende Pinto,
Bruno de Mattos Lombardi Badia,
José Laredo Filho,
Igor Braga Farias,
Paulo Victor Sgobbi de Souza,
Acary Souza Bullé Oliveira
Publication year - 2021
Language(s) - English
Resource type - Conference proceedings
DOI - 10.5327/1516-3180.552
Subject(s) - hereditary spastic paraplegia , dysphagia , spasticity , spastic , exome sequencing , medicine , spastic quadriplegia , family history , context (archaeology) , paraplegia , phenotype , biology , genetics , gene , physical therapy , spinal cord , surgery , cerebral palsy , psychiatry , paleontology
Context: Hereditary spastic paraplegias (HSPs) represent an expanding group of neurodegenerative diseases characterized mainly by progressive spastic paraparesis of the lower limbs. More than 80 different genetic loci have been associated with HSPs. In 2015, heterozygous pathogenic variants in the CPT1C gene were first associated with SPG73, not yet described in Brazilian patients. Objective: We present clinical, neuroimaging and genetic features of three Brazilian patients with SPG73. Cases reports: We report one male and two female patients, age range 36 to 78 years old. Case 1 presented with a 4-year-history of spasticity, predominantly crural tetraplegia, bladder incontinence, dysphagia and dysphonia. Family history disclosed a sister with epilepsy. Whole-exome sequencing (WES) disclosed a heterozygosis variant c.863G>A (p.Arg288His) in exon 9 of the CPT1C. Cases 2 and 3 are first degree relatives (mother and son). Both presented with long-standing slowly progressive spastic paraplegia. Case 3 presented bladder incontinence, constipation, dysphagia and dysphonia at late stages. Cases 2 and 3 WES disclosed the heterozygosis variant c.196T>G (p.Phe66Val) in exon 4 of the CPT1C. Discussion: Previous literature described six patients from an Italian family with pure HSPs phenotype and the pathogenic variant c.109C>G (p.Arg3. 7Cys) in CPT1C gene. Another group described three patients associated with pure HSPs phenotype and the pathogenic variant (c.226C>T) in the CPT1C gene. All previous reported cases had benign clinical course and bulbar involvement was not described before. One of our cases presented with a de novo variant and rapidly progressive motor and bulbar compromise. Conclusion: our cases expand the current knowledge about SPG73, including a rapidly progressive phenotype with bulbar involvement and cognitive compromise at late stages of disease course.