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Parkinson disease (familial)

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A 45-year-old man develops tremor, bradykinesia, and rigidity. Multiple family members across three generations have been affected with similar symptoms.

  • AD: SNCA (α-synuclein), LRRK2 (most common genetic cause)
  • AR: PRKN (parkin), PINK1, PARK7 (DJ-1) - usually earlier onset
  • Parkinsonism: Resting tremor, bradykinesia ("drive slowly in a PARKING lot"), cogwheel rigidity, postural instability → falls
  • Familial cases: younger onset, often <50 years
  • LRRK2: most common genetic form, later onset, similar to sporadic

Mnemonic: Parkin-syn = parkin, alpha synuclein

  • Primarily clinical: bradykinesia plus resting tremor and/or rigidity, with response to dopaminergic therapy
  • Consider genetic testing (panel including LRRK2, SNCA, PRKN, PINK1, PARK7) for early-onset or strong family history
  • DaTscan (dopamine transporter imaging) can support nigrostriatal degeneration when the diagnosis is uncertain
  • Symptomatic dopaminergic therapy: levodopa/carbidopa, dopamine agonists, MAO-B inhibitors
  • Deep brain stimulation for motor fluctuations and medication-refractory tremor
  • Physical, occupational, and speech therapy; manage non-motor symptoms (depression, constipation, sleep, orthostasis)
  • Genetic counseling tailored to the identified gene and inheritance pattern (AD vs AR)

LRRK2 - movements "Look Really Rigid"

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