Table 1 -.

Monogenic subtypes of Parkinson’s disease

			Clinical Phenotype Relative to ‘Classical’ PD
Genetic Entity	Mutation(s)	Inh.	AAO	Clinical Features	Progression	Comment(s)
Classical Parkinsonism (Autosomal Dominant Subtypes)
PARK-SNCA (PARK 1, 4)	missense (PARK1) dup./triplication (PARK 4)	AD	younger	similar, prominent NMS, early dementia	faster	rare
PARK-LRRK2 (PARK 8)	missense	AD	similar	similar (less RBD)	similar	common in Ashkenazi Jews, Basque country, North African Berbers; pleomorphic pathology
PARK-VPS35 (PARK 17)	missense	AD	similar	similar	similar	rare
PARK-CHCHD2 (PARK 22)	missense, splice site, nonsense	AD	similar	similar	similar	rare, Asian patients
Early-Onset Parkinsonism (Autosomal Recessive Subtypes)
PARK-Parkin (PARK 2)	missense, loss-of-function, exonic duplication, deletion	AR	younger	common early leg involvement & dystonia at onset, frequent dyskinesia	slow	common (accounts for up to 20% of PD with onset before age 50; dementia uncommon; no Lewy bodies
PARK-PINK1 (PARK 6)	missense, loss-of-function, exonic deletion, duplication	AR	younger	similar to PARK-Parkin, common psychiatric features	slow	second most common recessive PD subtype after PARK-Parkin, dementia uncommon
PARK-DJ1 (PARK 7)	missense, loss-of-function, small duplication/deletions	AR	younger	similar to PARK-Parkin, psychiatric symptoms	slow	rare, dementia uncommon
High-Risk Gene
GBA	missense, loss-of-function, small insertions/deletions	RG	younger	similar to sporadic PD, greater dementia risk	faster	very common (5–25% of PD patients), particularly in Ashkenazi Jews

Abbreviations: Inh: Inheritance; AD: autosomal dominant; AR: autosomal recessive; RG: risk gene; NMS: non-motor symptoms; RBD: REM sleep behavior disorder.