Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)

Recruiting

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

• Registration Number: NCT05354622
• Lead Sponsor: Boston Children's Hospital

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.

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:

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.

Study Timeline

• Study Start: 2022-04-25
• Study First Submitted: 2022-04-26
• Study First Submitted QC: 2022-04-26
• Study First Posted: 2022-04-29
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-10
• Last Update Posted: 2024-12-11
• Primary Completion: 2027-04-29
• Study Completion: 2027-04-29

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Clinical diagnosis of progressive spasticity

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States