Spastic ataxia

The clinical core of spastic ataxia is a progressive cerebellar syndrome combined with corticospinal-tract signs. Cerebellar features include gait unsteadiness, truncal instability, dysmetria, dysdiadochokinesis, dysarthria, and abnormal eye movements; pyramidal involvement typically manifests as lower-limb spasticity, hyperreflexia, and extensor plantar responses. Phenotypic expression is highly variable across genetic causes; additional features may include sensorimotor neuropathy, oculomotor apraxia, retinopathy, cognitive impairment, scoliosis, and pes cavus, with the relative prominence of cerebellar versus pyramidal involvement shifting between entities. Hereditary cerebellar ataxia and hereditary spastic paraplegia share overlapping molecular pathways and are increasingly
conceptualised as a continuous ataxia-spasticity disease spectrum, with individuals classified clinically as cerebellar ataxia carrying variants in genes traditionally assigned to hereditary spastic paraplegia. Age of onset is highly heterogeneous, ranging from early childhood, as seen in autosomal
recessive spastic ataxia of Charlevoix-Saguenay, through adolescence to adulthood, as documented for SPG7 and SYNE1-related ataxia.

No spastic-ataxia-specific prevalence figure is established. The prevalence of autosomal dominant cerebellar ataxias is estimated at 2.7 per 100,000 and of autosomal recessive cerebellar ataxias at 3.3 per 100,000; spastic ataxias represent a monogenic subset of both populations.

A large number of genes have been associated with spastic ataxia. The genetic forms can be grouped into autosomal recessive spastic ataxias and autosomal dominant spinocerebellar ataxias. Frequently identified causes include SPG7 (adult-onset variable spasticity with cerebellar ataxia) or ARSACS (SACS; early-onset ataxia with spastic paraparesis and neuropathy).

The genetic conditions associated with spastic ataxia follow heterogeneous inheritance patterns. Across the spectrum, autosomal recessive, autosomal dominant, and X-linked modes are documented. The inheritance mode varies by individual entity and is established through the molecular diagnosis.

• Where spastic ataxia is suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members and provides information relevant to family planning.

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