DRPLA

Excerpt

Clinical characteristics: DRPLA (dentatorubral-pallidoluysian atrophy) is a progressive neurologic disorder characterized by five cardinal features (irrespective of the age of onset): ataxia, cognitive decline, myoclonus, chorea, epilepsy, and psychiatric manifestations. Onset ranges from infancy to late adulthood (range: age 0-72 years; mean: age 31.5 years). The clinical presentation varies by age of onset: individuals with juvenile onset (before age 20 years) have myoclonus, epilepsy, and progressive intellectual deterioration, whereas individuals with adult onset (after age 20 years) have ataxia, choreoathetosis, and dementia or neuropsychiatric changes. Disease duration is on average eight years (range: 0-35 years) and age at death is on average 49 years (range: age 18-80 years).

Diagnosis/testing: The diagnosis of DRPLA is established in a proband with suggestive clinical findings and a heterozygous pathogenic CAG trinucleotide expansion in ATN1 identified by molecular genetic testing.

Management: Treatment of manifestations: Standard anti-seizure medications (ASMs) for seizures; appropriate psychotropic medications for psychiatric manifestations; symptomatic treatment of ataxia with riluzole and rehabilitation therapy; adaptation of environment and care to the level of dementia; appropriate educational programs for children.

Agents/circumstances to avoid: General anesthesia can increase the risk of intra- and postoperative seizures.

Pregnancy management: Because the use of ASMs during pregnancy may have an effect on the fetus, discussion of the risks and benefits of using an ASM during pregnancy should ideally occur prior to conception when transition to a lower-risk medication may be possible. The use of riluzole during pregnancy has not been well studied in humans.

Genetic counseling: DRPLA is inherited in an autosomal dominant manner. The risk to the children of an affected individual of inheriting an expanded CAG repeat is 50%. The size of the repeat transmitted to the offspring depends on the size of the parent's repeat and the sex of the transmitting parent. Once an abnormal CAG repeat expansion in ATN1 has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.