Spastic Paraplegia 8

Clinical characteristics: Hereditary spastic paraplegia 8 (SPG8) is a slowly progressive pure spastic paraplegia of the lower limbs (i.e., pyramidal signs including hyperreflexia, spasticity, and occasionally clonus without other neurologic findings). Some affected individuals have urinary urgency that usually becomes apparent at the same time as the spasticity. Onset is between ages ten and 59 years. Affected individuals often become wheelchair dependent. While intra- and interfamilial phenotypic variability is high, SPG8 is typically more severe than other types of hereditary spastic paraplegia.

Diagnosis/testing: The diagnosis of SPG8 is established in a proband with suggestive clinical findings and a heterozygous pathogenic variant in WASHC5 identified by molecular genetic testing.

Management: Treatment of manifestations: A multidisciplinary approach to management of spasticity is recommended including neurology, physical therapy (PT), occupational therapy (OT), urology, speech and language pathology, feeding team, psychiatry/mental health, and social work.

Surveillance: Regular neurologic examinations to evaluate disease progression and response to treatment; urologist for assessment of bladder function and risk for urinary tract infection; PT/OT to assess mobility and activities of daily living; feeding team for nutrition and risk for aspiration; speech and language pathologist re dysarthria; and mental health clinician re depression.

Genetic counseling: SPG8 is inherited in an autosomal dominant manner. More than 90% of individuals with SPG8 have an affected parent. Each child of an individual with SPG8 has a 50% chance of inheriting the WASHC5 pathogenic variant. Once the WASHC5 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.