Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)

NCT ID: NCT05354622

Last Updated: 2024-12-11

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-04-25
• Study Completion Date: 2027-04-29

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.

Conditions

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

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Clinical diagnosis of progressive spasticity

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boston Children's Hospital - Children's Rare Disease Cohorts Initiative

UNKNOWN

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Darius Ebrahimi-Fakhari

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Darius Ebrahimi-Fakhari, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Locations

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Darius Ebrahimi-Fakhari, MD, PhD

Role: CONTACT

Phone: 617-355-8356

Email: hsp.research@childrens.harvard.edu

Amy Tam, BS

Role: CONTACT

Phone: 617-355-2698

Email: hsp.research@childrens.harvard.edu

Facility Contacts

Amy Tam

Role: primary

Other Identifiers

P00039630

Identifier Type: -

Identifier Source: org_study_id