Table 3a.

Genes Associated with Early-Onset Adult Parkinson Disease (Age 20-50 Years) and Late-Onset Adult Parkinson Disease (Age >50 Years)

Gene 1PD Designation 2MOI% of Adult PDComments
GBA1 (GBA) 3PARK-GBA (OMIM 606463)AD3%-7%
(20% in AJ ancestry)
  • Onset age may be <50 yrs.
  • Higher likelihood of cognitive impairment & atypical motor findings
  • Faster progression
  • Assoc w/dementia w/Lewy bodies
  • Variable penetrance dependent on age, variant, & ethnicity
  • Consider if family history of Gaucher disease.
LRRK2 PARK-LRRK2
(See LRRK2 PD.)		AD1%-2%
(13%-30% in AJ ancestry; 41% in African Berber ancestry)
  • Classic manifestations w/less non-motor involvement
  • Variable penetrance dependent on age, variant, & ethnicity
PARK7
(DJ1)		PARK-DJ1 (OMIM 606324)ARRare
  • Phenotype similar to PARK-Parkin
  • ID &/or seizures occasionally
  • Risk to heterozygotes unknown
PINK1 PARK-PINK1
(See PINK1 Type of Young-Onset PD.)		ARRare
(3.7% of early-onset adult PD)
  • Phenotype similar to PARK-Parkin
  • Non-motor manifestations (incl psychiatric features) more common
  • Heterozygotes may have ↑ PD risk.
PRKN PARK-Parkin
(See Parkin Type of Early-Onset PD.)		AR1%
(4.6%-10.5% of early-onset adult PD)
  • Slow progression
  • Can have lower-limb dystonia, dyskinesias, hyperreflexia
  • Mild non-motor manifestations
  • Heterozygotes may have ↑ PD risk.
SNCA PARK-SNCA (OMIM 168601, 605543)ADRare
  • Onset age may be <50 yrs.
  • Cognitive & psychiatric features more likely
VPS13C PARK-VPS13C (OMIM 616840)ARRare
  • Early-onset PD w/very rapid progression
  • Truncating variants cause severe disease.

Based on Dulski et al [2022], Dulski et al [unpublished data]

AD = autosomal dominant; AJ = Ashkenazi Jewish; AR = autosomal recessive; ID = intellectual disability; MOI = mode of inheritance; PD = Parkinson disease

1.

Genes are listed in alphabetic order.

2.

Nomenclature based on Lange et al [2022]

3.

There is some disagreement among researchers as to whether GBA1 should be classified as a monogenic disorder or, alternatively, a risk factor – due to its low age-related penetrance (see Parkinson Disease Overview).

From: VPS35-Related Parkinson Disease

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