When to Question Cerebral Palsy: Hereditary Spastic Paraplegia Masquerading as Cerebral Palsy
Objective:
To describe a case of progressive lower-extremity weakness initially attributed to CP and subsequently reclassified as HSP following genetic testing.
Background:
Cerebral palsy (CP) is one of the most common diagnoses in pediatric neurology, classically defined as a non-progressive, permanent motor disorder from early brain injury. Advances in genetic testing have increasingly identified hereditary spastic paraplegia (HSP) as an alternative diagnosis in a subset of patients labeled with spastic diplegic CP. SPAST gene (SPG4) mutations represent the most common form of HSP. Unlike CP, HSP typically follows a slowly progressive course that may not become apparent until adulthood, contributing to diagnostic delays.
Results:
A 39-year-old man with a history of spastic diplegic CP presented with progressive lower extremity weakness. He was born at term with a delayed initial cry but otherwise normal early development. At age 3, he was diagnosed with CP due to bilateral leg weakness and spasticity. He ambulated independently in childhood with an abnormal gait and remained stable until his late 20s, when gradual worsening of weakness and gait impairment led to walker use and, by age 32, wheelchair dependence.
Neurologic examination revealed marked lower extremity spasticity with diffuse hyperreflexia, consistent with a pure upper motor neuron process. Electromyography and nerve conduction studies were normal. Given the progressive phenotype and lack of clear perinatal injury, genetic testing for HSP was performed, identifying a heterozygous pathogenic SPAST variant. Family history was negative, suggesting a de novo mutation. Baclofen titration was initiated, and genetic counseling with cascade testing was arranged.
Conclusions:
This case highlights the importance of considering HSP in patients with spastic diplegia, particularly without clear perinatal insult and with progressive symptoms. Early genetic testing may prevent prolonged misdiagnosis and enable timely intervention, counseling, and family risk assessment.
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