SCA17, also known as Huntington disease-like 4, is a neurodegenerative disorder characterized by ataxia, involuntary movements, dementia and cerebellar atrophy. Affected individuals may exhibit gait and limb ataxia, pyramidal signs, dysarthria, apraxia, dystonia, bradykinesia, myoclonus and ocular movement anomalies. Psychiatric manifestations of the condition include paranoia, hallucinations, aggression, disorientation and depression. Brain imaging studies of patients reveal cerebellar and diffuse cerebral atrophy as well as neuronal loss and gliosis in the striatum, medial thalamic nuclei and inferior olives. SCA17 is a rare type of spinocerebellar ataxia that has affected less than 100 families worldwide. The condition has a median onset at around 23 years of age. However, SCA17 is a highly variable disorder and the severity, presentation and progression can differ even between family members. The prognosis is currently poor, with many patients succumbing to the condition by the sixth decade of life.
Diagnosis is made based on clinical features, neurological imaging studies and molecular analysis of the TBP gene. Treatment may include psychotropic drugs for psychiatric symptoms, anti-epileptic drugs for seizures and local administration of botox for dystonia, as well as physical and occupational therapy. Affected families may benefit from genetic counselling and prenatal testing.
Monies et al. (2017) characterized the genomic landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. One patient, a 28-year-old female, presented with a familial disease with mental subnormality, walking difficulties and abnormal movement. Whole exome sequencing helped identify a homozygous mutation (c.171delG, p.Q57 fs) in exon 2 of the patient’s TBP gene. As TBP is associated with autosomal dominant spinocerebellar ataxia 17, this finding presented a unique case of a recessive mutation in a gene normally associated with a dominant phenotype.