Parkin Type of Early-Onset Parkinson Disease

Excerpt

Clinical characteristics: Parkin type of early-onset Parkinson disease (PARK-Parkin) is characterized by the cardinal signs of Parkinson disease (PD): bradykinesia, resting tremor, and rigidity. The median age at onset is 31 years (range: 3-81 years). The disease is slowly progressive: disease duration of more than 50 years has been reported. Clinical findings vary; hyperreflexia is common. Lower-limb dystonia may be a presenting sign and cognitive decline appears to be no more frequent than in the general population. Dyskinesia as a result of treatment with levodopa frequently occurs.

Diagnosis/testing: The diagnosis of PARK-Parkin is established in a proband with suggestive findings and biallelic pathogenic variants in PRKN identified by molecular genetic testing.

Management: Treatment of manifestations: Levodopa and dopamine agonists, MAO B inhibitors, COMT inhibitors, and amantadine; deep brain stimulation for those experiencing difficulty with levodopa therapy.

Surveillance: Neurologic follow up including assessment of treatment every six to 12 months.

Agents/circumstances to avoid: Use of levodopa therapy that exceeds the dose needed for satisfactory clinical response. Neuroleptic treatment may exacerbate parkinsonism.

Genetic counseling: PARK-Parkin is inherited in an autosomal recessive manner. At conception, each sib of a proband has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier. Once the PRKN pathogenic variants in a family are known, carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible.