hereditary spastic paraplegia genomic sequencing initiative (hspseq)

Conditions: Hereditary Spastic Paraplegia; Neurodegenerative Diseases; Pediatric Disorder; Spasticity, Muscle; Motor Neuron Disease; Movement Disorders

Summary: the purpose of the hsp sequencing initiative is to better understand the role of genetics in hereditary spastic paraplegia (hsp) and related disorders. the hsps are a group of more than 80 inherited neurological diseases that share the common feature of progressive spasticity. collectively, the hsps present the most common cause of inherited spasticity and associated disability, with a combined prevalence of 2-5 cases per 100,000 individuals worldwide. in childhood-onset forms, initial symptoms are often non-specific and many children may not receive a diagnosis until progressive features are recognized, often leading to a significant diagnostic delay. genetic testing in children with spastic paraplegia is not yet standard practice. in this study, the investigators hope to identify genetic factors related to hsp. by identifying different genetic factors, the investigators hope that over time we can develop better treatments for sub-categories of hsp based on cause.

the hereditary spastic paraplegias (hsp) are a group of more than 80 inherited neurogenetic diseases that share the common feature of progressive spasticity. collectively, the hsps present the most common cause of inherited spasticity and associated disability, with a combined prevalence of 2-5 cases per 100,000 individuals worldwide. in childhood-onset forms, initial symptoms are often non-specific and many children may not receive a diagnosis until progressive features are recognized, often leading to a significant diagnostic delay. genetic testing in children with spastic paraplegia is not yet standard practice. the clinical diagnosis of hsp does not suggest anything about its molecular cause, with a wide range of outcomes dependent on the gene affected. the recent advances in hsp genetics speak to the importance of the field and the need for a more detailed study. moreover, the relations between clinical features and genetic mechanisms are not well understood. given the influence of genetics on the likelihood of developing hsp as well as the complexity and diversity of the phenotypes, progress in hsp genetics will require efforts looking at relatively large samples of the hsp population. by bringing together very detailed phenotype information with high resolution dna analyses, and using new approaches for comparing sequence information in candidate genes or looking for phenotype/genotype associations via genome-wide scanning, the investigators aim to be a leader in this emerging area of hsp research. the aims of this study include: 1. to identify genetic findings (single nucleotide changes or copy number variants) in patients with progressive spastic paraplegia and related disorders. 2. to correlate molecular findings with hsp phenotypes.

Eligibility criteria:
inclusion criteria: * clinical diagnosis of progressive spasticity

Keywords: hereditary spastic paraplegia neurodegenerative disease spasticity spg3a spg4 spg11 spg15 spg26 spg47 spg50 spg51 spg52 complex hereditary spastic paraplegia early onset hereditary spastic paraplegia movement disorder adaptor protein complex 4 neurogenetic disorder genetic disease muscle spasticity neurodevelopmental disorders musculoskeletal disease