Clinical trial NCT05354622: Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)
Official title: Investigating the Genetic Basis of Hereditary Spastic Paraplegia
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: Boston Children's Hospital - Children's Rare Disease Cohorts Initiative
First posted: 2022-04-29
Enrollment: 200
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male or female, under 30 years, with suspected HSP

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.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of progressive spasticity

Primary outcomes:
measure: Identify Genetic Findings
timeFrame: An average of 1 year
measure: Correlating Genetic Findings with HSP Phenotypes
timeFrame: An average of 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Darius Ebrahimi-Fakhari, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: