Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)

Sponsor

Boston Children's Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05354622

Collaborator

Boston Children's Hospital - Children's Rare Disease Cohorts Initiative (Other)

200

Enrollment

Location

60.1

Anticipated Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Hereditary Spastic Paraplegia Neurodegenerative Diseases Pediatric Disorder Spasticity, Muscle Motor Neuron Disease Movement Disorders

Detailed Description

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:

To identify genetic findings (single nucleotide changes or copy number variants) in patients with progressive spastic paraplegia and related disorders.
To correlate molecular findings with HSP phenotypes.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

200 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Investigating the Genetic Basis of Hereditary Spastic Paraplegia

Actual Study Start Date :

Apr 25, 2022

Anticipated Primary Completion Date :

Apr 29, 2027

Anticipated Study Completion Date :

Apr 29, 2027

Outcome Measures

Primary Outcome Measures

Identify Genetic Findings [An average of 1 year]
Identifying genetic variants in patients with progressive spastic paraplegia
Correlating Genetic Findings with HSP Phenotypes [An average of 1 year]
Comparing phenotype/genotype associations via genome wide scanning