Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)

Investigating the Genetic Basis of Hereditary Spastic Paraplegia

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.

Study Overview

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

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 Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Darius Ebrahimi-Fakhari, MD, PhD; Phone Number: 617-355-8356; Email: hsp.research@childrens.harvard.edu
• Study Contact Backup: Name: Amy Tam, BS; Phone Number: 617-355-2698; Email: hsp.research@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Amy Tam; Phone Number: 617-355-2698; Email: amy.tam@childrens.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Male or female, under 30 years, with suspected HSP

Description

Inclusion Criteria:

• Clinical diagnosis of progressive spasticity

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: Boston Children's Hospital - Children's Rare Disease Cohorts Initiative
• Investigators: Principal Investigator: Darius Ebrahimi-Fakhari, MD, PhD, Boston Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2022
• Primary Completion (Estimated): April 29, 2027
• Study Completion (Estimated): April 29, 2027

Study Registration Dates

• First Submitted: April 26, 2022
• First Submitted That Met QC Criteria: April 26, 2022
• First Posted (Actual): April 29, 2022

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Spasticity; Genetic Disease; Neurodegenerative disease; Muscle Spasticity; Musculoskeletal Disease; Movement disorder; Neurodevelopmental disorders; Hereditary Spastic Paraplegia; Neurogenetic disorder; SPG11; SPG4; SPG3a; SPG15; SPG26; SPG47; SPG50; SPG51; SPG52; Complex hereditary spastic paraplegia; Early Onset hereditary spastic paraplegia; Adaptor protein complex 4
• Additional Relevant MeSH Terms: Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Muscular Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Mental Disorders; Neuromuscular Diseases; Peripheral Nervous System Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Hereditary Sensory and Motor Neuropathy; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Muscle Spasticity; Neurodevelopmental Disorders; Genetic Diseases, Inborn; Movement Disorders; Motor Neuron Disease; Musculoskeletal Diseases; Neurodegenerative Diseases; Spastic Paraplegia, Hereditary; Spastic paraplegia 3, autosomal dominant; Spastic paraplegia 26, autosomal recessive
• Other Study ID Numbers: P00039630

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No