This page is dedicated to the Hereditary Spastic Paraplegia and Related Movement Disorders research study, one of 57 studies supported by the Boston Children’s Rare Disease Collaborative (CRDC). For more information about the CRDC, please visit our home page. Established in 2018, the CRDC supports pediatric rare disease research and provides families with genetic diagnoses that enable personalized treatments, including precision medicine and targeted therapies.
The Hereditary Spastic Paraplegia and Related Movement Disorders research study, established at Boston Children’s in 2022 and led by Dr. Darius Ebrahimi-Fakhari, has already enrolled 70 patients and their families.
Hereditary spastic paraplegia (HSP) refers to a group of more than 80 genetic conditions that present with progressive spasticity (muscle tightness) and weakness in the legs. The degree of weakness is variable and ranges from no weakness (full strength) to significant weakness (paraplegia). Learn more about HSP at Boston Children’s.
Key Outcomes
To date, 35% of patients received clinical results leading to changes in treatment plans and an additional 52% have candidate findings that are being further researched.
Genes Associated with HSP
ABHD16A, ABCD1, ACER3, ACP33, AFG3L2, ALDH18A1, AMFR, AP4B1, AP4E1, AP4M1, AP4S1, ARL6IP1, ATL1, BICD2, BSCL2, C12orf65, C19orf12, CCT5, CERS1, CLN8, CNTNAP1, COQ4, CPT1C, CYP2U1, DDHD1, DDHD2, DSTYK, ERLIN2, FA2H, FARS2, GBA2, GJC2, GLE1, HACE1, HSPD1, KIF1A, KIF1C, KIF5A, NIPA1, NT5C2, PGAP1, PGAP3, PNPLA6, REEP1, RINT1, RTN2, SCN1A, SLC16A2, SLC33A1, SLC39A14, SPAST, SPG11, SPG15, SPG21, SPG7, TFG, TREX1, VPS37A, WASHC5, ZFYVE26, ZFYVE27
Participate in Research
Physicians may refer their patients with diagnoses of HSP to Dr. Ebrahimi-Fakhari. Once study eligibility is confirmed, a research coordinator will reach out to the family to consent and enroll them. Read more about Dr. Ebrahimi-Fakhari’s studies on the Ebrahimi-Fakhari Lab webpage.
Patient Care
Patients and their families with HSP can be seen by an expert multidisciplinary team in the Movement Disorders Program at Boston Children’s.
Patient Stories
A 2-year-old girl was evaluated in Sweden for symptoms resembling hereditary spastic paraplegia. After finding no clinical explanation for her condition and negative clinical genetic testing, the team in Sweden collaborated with Dr. Ebrahimi-Fakhari’s team and the CRDC to enroll the girl in this study. Whole genome sequencing and analysis revealed a mutation in the RINT1 gene, which was just described by a team of researchers in Spain as a new gene associated with hereditary spastic paraplegia. This girl is only the fourth patient in the world known to carry this mutation. The significance of this discovery cannot be overstated. Not only did it provide the family with a long-awaited genetic explanation and diagnosis, but it also prompted changes in this patient’s care plan, which includes regular monitoring of the liver function and avoiding medications that can trigger liver failure, as this gene mutation can lead to acute liver failure. Notably, this discovery led to an international collaboration between the teams in Boston Children’s, Sweden, and Spain to further investigate this gene and advance the understanding of hereditary spastic paraplegia.
Investigators
Divisions
Notable Publications by Investigators
- Biallelic variants in RINT1 present as early-onset pure hereditary spastic paraplegia
- Biallelic Variants in COQ4 Cause Childhood-Onset Pure Hereditary Spastic Paraplegia
Disease Support Organizations
Spastic Paraplegia Foundation
The Spastic Paraplegia Foundation is dedicated to advancing research and finding cures for two groups of closely related, progressive neurological disorders: primary lateral sclerosis (PLS) and hereditary spastic paraplegia (HSP).