Parkinson Disease

CLINICAL CHARACTERISTICS

Parkinson disease is a complex early-onset neurologic disorder whose core features are typical parkinsonian symptoms including bradykinesia, resting tremor, rigidity, and postural instability. The majority of individuals have juvenile onset and develop symptoms before age 21 years. Developmental delay, intellectual disability, seizures, other movement disorders (e.g., dystonia, spasticity, myoclonus), and neuropsychiatric features occur in the majority of individuals with juvenile onset and often precede parkinsonism. The onset of parkinsonian features usually occurs toward the end of the first or beginning of the second decade and the disease course is rapidly progressive with loss of ambulation in mid-adolescence in the majority of individuals. Additional features include gastrointestinal manifestations and bulbar dysfunction. A minority of individuals with Parkinson disease develop early-onset parkinsonism with symptom onset in the third to fourth decade and absence of additional neurologic features.

DIAGNOSIS/TESTING: The diagnosis of Parkinson disease is established in a proband with suggestive phenotypic findings and biallelic pathogenic variants in identified by molecular genetic testing.

MANAGEMENT

Levodopa, dopaminergic agonists, and/or anticholinergics. Medications and/or surgical interventions for dystonia and spasticity. Medications (e.g., sodium valproate, clonazepam, levetiracetam, piracetam) as needed for myoclonus. Multidisciplinary management including physical and occupational therapy, speech and language therapy, and special education services as indicated for developmental delay and intellectual disability. Seizures are treated with anti-seizure medication. Psychiatric disorders are treated as per neuropsychiatry. Sleep aids (e.g., sleep system, conservative measures, melatonin, sedative medications) as needed for sleep disorder. Feeding support and medications as needed for constipation, sialorrhea, and reflux. Supportive rehabilitation devices and equipment for orthopedic manifestations. Surgical interventions as needed for hip dislocation or kyphoscoliosis. Low-vision therapy, glasses, and surgical intervention as needed for strabismus and/or vision deficits. : Physical therapy, occupational therapy, and speech and language therapy evaluations every six months or as needed. Assess for new manifestations such as seizures, changes in tone, and movement disorders at each visit. Repeat electroencephalogram as needed. Monitor those with seizures as clinically indicated. Psychiatric assessment as needed. Sleep study/polysomnography as needed. Growth assessment at each visit in children. Assessment of nutritional status at each visit. Swallowing assessment to evaluate risk of aspiration as needed. Gastroenterology evaluation and gastroscopy as needed. Hip and spine radigraphs every six months in individuals older than age two years who are nonambulatory and in individuals with signs and symptoms concerning for spinal deformity. Follow-up ophthalmology evaluation for those with vision concerns. Dopamine antagonists and vesicular monoamine transporter 2 (VMAT2) inhibitors should be avoided as they could aggravate dopamine deficiency.

GENETIC COUNSELING

Parkinson disease is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being heterozygous, and a 25% chance of inheriting neither pathogenic variant. (Note: The risk to heterozygotes of developing manifestations is not yet determined.) Once the pathogenic variants have been identified in an affected family member, heterozygote testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.