Spinocerebellar Ataxia Type 37

Excerpt

Clinical characteristics: Spinocerebellar ataxia type 37 (SCA37) is characterized by adult onset, dysarthria, slowly progressive gait and limb ataxia with severe dysmetria in the lower extremities, mild dysmetria in the upper extremities, dysphagia, and abnormal ocular movements (dysmetric vertical saccades, irregular and slow vertical smooth pursuit, slow vertical optokinetic nystagmus, and oscillopsia (visual disturbance in which objects appear to oscillate). In most individuals, the initial signs/symptoms include falls, dysarthria, or clumsiness followed by a complete cerebellar syndrome. A distinctive clinical feature is the presence of altered vertical eye movements in early stages of the disease, even preceding ataxia symptoms. Clinical progression is slow and affected individuals usually become wheelchair bound between ten and 33 years after disease onset.

Diagnosis/testing: The diagnosis of SCA37 is established in a proband by identification of a heterozygous ATTTC repeat insertion within DAB1 by molecular genetic testing. All affected persons have 31-75 ATTTC repeats, flanked on both sides by polymorphic ATTTT repeats over 58 units.

Management: Treatment of manifestations: Currently, no treatment reverts the course of the disease. Speech therapy to improve communication and ameliorate dysphagia; thickness modification of food and fluids to prevent aspiration; physical therapy to train balance; use of external devices (e.g., canes or walkers) when needed to avoid falls; occupational/behavioral therapy.

Surveillance: Scale for the Assessment and Rating of Ataxia (SARA) score annually; electrooculographic tests may be performed every two years (cooperation required); brain MRI volumetry every two years.

Genetic counseling: SCA37 is inherited in an autosomal dominant manner. All individuals diagnosed to date with SCA37 have an affected parent. Each child of an individual with SCA37 is at a 50% risk of inheriting the intronic ATTTC repeat insertion within DAB1. Prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible if the ATTTC repeat insertion within DAB1 has been identified in an affected family member.