Spinocerebellar Ataxia Type 28

Excerpt

Clinical characteristics: Spinocerebellar ataxia type 28 (SCA28) is characterized by young-adult onset, very slowly progressive gait and limb ataxia resulting in coordination and balance problems, dysarthria, ptosis, nystagmus, and ophthalmoparesis. In most individuals, SCA28 presents as a loss of coordination of lower limbs (unsteadiness, gait ataxia). Less frequently, ptosis/ophthalmoplegia, dysarthria, or upper-limb incoordination may occur as the initial finding. The course of the disease is slowly progressive without impairment of functional autonomy even decades after onset.

Diagnosis/testing: Because the phenotype of SCA28 is indistinguishable from many other inherited disorders with SCA, the diagnosis of SCA28 is established in a proband with typical clinical findings by the identification of a heterozygous pathogenic variant in AFG3L2 by molecular genetic testing.

Management: Treatment of manifestations: Ambulatory aids (crutches, canes, walkers); home adaptations as needed; physical therapy to help with tasks such as eating, dressing, walking, and bathing; stretching exercise for those with pyramidal involvement to avoid contractions and lack of comfort during sleep. Speech/ language therapy is helpful for those with dysarthria and swallowing difficulties as is surgery for severe ptosis.

Prevention of secondary complications: Psychological support; weight control to facilitate ambulation; thickened feeds or gastrostomy feedings to avoid aspiration pneumonia.

Surveillance: Annual assessment to evaluate stability or progression of the cerebellar ataxia. Monitoring of speech and swallowing.

Agents/circumstances to avoid: Alcohol consumption and sedatives such as benzodiazepines that may worsen gait ataxia and coordination.

Genetic counseling: SCA28 is inherited in an autosomal dominant manner. Most individuals diagnosed with SCA28 have an affected parent; the proportion of cases caused by de novo pathogenic variants is unknown. Each child of an individual with SCA28 has a 50% risk of inheriting the pathogenic variant. Prenatal and preimplantation genetic testing are possible if the pathogenic variant in the family has been identified.