Parkinson disease (PD) is a progressive neurodegenerative disorder manifested by a broad spectrum of motor and non-motor features. Characteristic features of PD include neuronal loss in specific areas of the Substantia nigra and widespread intracellular protein α-synuclein accumulation. The disease is characterized by three core motor symptoms: tremor, muscle rigidity and bradykinesia.
The typical age of onset is around 60 years; however, it can be earlier. Onset before age 20 is considered to be juvenile-onset PD and before age 50 is considered to be early-onset PD.
CENTOGENE’s Parkinson disease panel for the hereditary variants of PD has been carefully selected to identify pathophysiologically relevant genetic variants for the development and treatment of PD.
- Autosomal dominant
- Autosomal recessive
13-19/100,000 annual incidence rate.1,2
Initial clinical symptoms of Parkinson disease include the following:
- Decreased facial expression
- Sleep disturbances
- Abnormal eye movement
- Sensory disturbances e.g. decreased sense of smell
- Symptoms of autonomic dysfunction (constipation, sweating abnormalities, sexual dysfunction, seborrheic dermatitis)
- Weakness, fatigue
- Depression or anhedonia
- Postural instability
- Decreased arm swing on the first-involved side
Onset of motor signs includes the following:
- Typically, asymmetric resting tremor in an upper extremity
- Progression of bradykinesia, rigidity, and gait difficulty
- Axial posture becomes progressively flexed and strides become shorter
Diagnosis is based on clinical criteria and requires the presence of two of the first three features:3-5
- Resting tremor
- Postural instability
- Substantial and sustained response to levodopa or a dopamine agonist
- Neuroimaging can be helpful to differentiate PD from other motor, hypokinetic diseases.
- Levodopa (L-dopa)6,7
- Dopaminergic agonists
- Anticholinergic agents
- Monoamine oxidase-B inhibitors
- Deep brain stimulation (DBS)
- Exercise-based treatment.
- Lewy body dementia
- Multiple system atrophy
- Progressive supranuclear palsy
- Corticobasal degeneration
- Essential tremor
- Drug-induced parkinsonism
- Alzheimer disease
To confirm/establish the diagnosis, CENTOGENE offers the following tests:
- Parkinson disease NGS Panel which includes sequencing of the genes ATP13A2, ATP1A3, ATP6AP2, DCTN1, DNAJC6, FBXO7, FTL, FUS, GBA, GCH1, HTRA2, LRRK2, MAPT, PARK2, PARK7, PINK1, PLA2G6, PRKRA, SLC30A10, SLC6A3, SNCA, SNCB, SPR, SYNJ1, TAF1, TH, TMEM230, UCHL1, VPS35
- Parkinson disease NGS Panel + CNV which includes sequencing and additionally detection of large deletions and duplications from the NGS data for the above genes
- Individuals with clinical symptoms consistent with the disease, with or without a positive family history (diagnostic testing)
- Family members without clinical symptoms but at-risk of harbouring a mutation that can lead to the development of the disease in future (predictive testing)
- Family members who are not at risk of developing the disorder but at risk of carrying a known familial mutation (carrier testing)
Confirmation of a clinical diagnosis through genetic testing can allow for genetic counseling and may direct medical management. Genetic counseling can provide a patient and/or family member with the natural history of the condition, identify at-risk family members, provide reproductive risks, explain preconception/prenatal options, and ensure appropriate referral for patient support and access to information resources.