What is hereditary spastic paraplegia?
Hereditary spastic paraplegia (HSP) refers to a group of over 80 different genetic conditions that present with progressive spasticity (muscle tightness) and weakness. Many forms of HSP are rare or even ultra-rare diseases.
There may be significant variation in the severity of leg weakness (varying from none to marked), the degree of spasticity (varying from minimal to severe), and the occurrence of other neurologic symptoms between different genetic types of HSP; as well differences in the nature and severity of symptoms between individuals who have exactly the same genetic type of HSP.
Hereditary Spastic Paraplegia | Symptoms
What are the symptoms of HSP?
The primary symptom of HSP is difficulty walking due to spasticity and weakness in the legs. Both legs are affected, usually to a relatively similar degree. The term “paraplegia” means severe weakness in both legs (similar to “paralysis”). “Paraparesis” indicates weakness in both legs of lesser severity than paraplegia. Although the disorder is typically referred to as hereditary spastic paraplegia, the degree of weakness is variable and ranges from no weakness (full strength) to marked weakness (paraplegia).
Spasticity primarily affects muscles of leg extension, knee flexion, hip adduction (bringing the knees together), and muscles that extend the feet.
Toe walking is often an early symptom, and the walking pattern may eventually be described as a “spastic gait.” Tightness in the legs and leg muscle spasm (often at night) are not uncommon.
Additional symptoms are variable depending on the subtype of HSP. Historically, “uncomplicated” or “pure” HSP refers to a combination of spastic weakness and urinary urgency. Many childhood-onset forms of HSP present with additional symptoms and are therefore called “complicated” or “complex” HSP. This may include developmental delays, intellectual disability, impaired speech, seizures, difficult with coordination (ataxia) or other movement disorders, and impaired vision or hearing. In some forms of HSP a small head size (microcephaly) or developmental brain malformations are common.
When HSP begins in early childhood, the initial symptoms are often non-specific. The symptoms may initially resemble the symptoms seen in cerebral palsy, a life-long disorder that remains relatively stable. It is important to recognize that HSP is different from cerebral palsy, and early genetic testing can shorten the time to a diagnosis.
Hereditary Spastic Paraplegia | Diagnosis & Treatments
How do we diagnose HSP?
The diagnosis of HSP is based on a neurological examination and other tests:
- typical symptoms (spastic and weakness of the legs)
- findings on neurologic examination (lower extremity hyperreflexia, usually accompanied by some degree of spasticity and sometimes a specific pattern of muscle weakness)
- the exclusion of alternate disorders (by history, examination, neuroimaging, and laboratory studies as needed)
A number of specialized tests may be used in the diagnostic evaluation for HSP, including laboratory tests, genetic testing, MRI scans of the brain and spine, EEG, and nerve conduction tests or an EMG.
Genetic testing is often able to identify a causative gene mutation. Despite discovery of more than 80 genes in which mutations cause various types of HSP, some individuals with HSP do not have an identified gene mutation. This is because:
- genes for all types of HSP have not been discovered
- some discovered genes are not yet included in clinical testing panels
- methods of gene sequencing and interpretation are variable
Our program offers specialized testing on a clinical and research basis.
How do we treat hereditary spastic paraplegia?
There is currently no cure for HSP. Available treatment can reduce symptoms and prevent complications. This may include physical therapy, occupational therapy, speech therapy, and other developmental supports; medications that reduce spasticity, injection of botulinum toxin, orthotics, and certain surgical procedures.
Treatment requires an interdisciplinary approach, which may include referrals to several programs and services. The Movement Disorders Program at Boston Children’s Hospital is home to specialists with a variety of backgrounds and areas of focus. As a team, this diversity makes us better prepared to care for each child's unique needs.
At Boston Children’s Hospital, we care for patients with HSP in the Movement Disorders Program at the Department of Neurology, and in some case, the Neuromuscular Center, the Cerebral Palsy and Spasticity Center, and the Clinical Genetics Program.
Hereditary Spastic Paraplegia | Research
The Movement Disorders Program in the Department of Neurology is committed to patient care, education, advocacy, and research. Many forms of HSP that present in childhood are rare diseases. Research holds the key to improving the diagnosis and treatment of these conditions.
Current research studies for HSP include:
- Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)
- ClinicalTrials.gov Identifier: NCT05354622
- Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia (HSP)
- ClinicalTrials.gov Identifier: NCT04712812
Information on current clinical trials are posted at www.clinicaltrials.gov.
Families interested in more information about research on HSP should contact Catherine Jordan:
- Phone: 617-355-2698
- Email: Catherine.Jordan@childrens.harvard.edu or AP4HSP.email@example.com