Table 3.

Genes Associated with Early-Onset Autosomal Recessive Parkinson Disease and Parkinsonism in the Differential Diagnosis of DNAJC6 Parkinson Disease

GenePD
Designation 1		Median Age
at Onset
(Range) 2		Number of
Persons 2, 3		Comment
ATP13A2 PARK-ATP13A2 (Kufor-Rakeb syndrome) (OMIM 606693)14 (0-30) yrs36Pyramidal signs, eye movement abnormalities, T2-weighted basal ganglia hypointensity, cerebral & cerebellar atrophy, brain stem atrophy
DJ-1 PARK-DJ-1 (OMIM 606324)27 (15-40) yrs33Phenotype similar to PARK-Parkin; ID, DD &/or seizures occasionally; risk to heterozygotes unknown
FBXO7 PARK-FBXO7 (OMIM 260300)17 (10-52) yrs27ID/DD/early cognitive impairment, early & vivid hallucinations & behavioral abnormalities w/intake of dopamine agonists, early falls, saccadic abnormalities, gaze palsy, oculogyric spasms, pyramidal signs, autonomic dysfunction
GBA1 (GBA)PARK-GBAMay be <50 yrs; median onset: ~60 yrs 4>100Severe motor impairment & rapid progression (akinetic-rigid onset), early onset of cognitive decline, neuropsychiatric & autonomic vulnerability
PINK1 PARK-PINK1 32 (9-67) yrs1512nd most common cause of EOPD; heterozygotes may have ↑ PD risk 5.
PRKN PARK-Parkin 31 (3-81) yrs>1000Most common cause of EOPD; dystonia, hyperreflexia 5
SYNJ1 PARK-SYNJ1 (OMIM 615530)21 (12-31) yrs15Early cognitive impairment, early falls, saccadic abnormalities, gaze palsy, pyramidal signs, ataxia, autonomic dysfunction
VPS13C PARK-VPS13C (OMIM 616840)29 (0-70) yrs4Early cognitive impairment, early falls, pyramidal signs, autonomic dysfunction
SPG11 Spastic paraplegia 11 (SPG11)Typically in infancy or adolescence 6; median onset of parkinsonism: ~15 yrs5 (atypical parkinsonism)Progressive spastic paraparesis, cognitive impairment, axonal neuropathy, MRI abnormalities (thin corpus callosum, T2 periventricular white matter hyperintensities)
ZFYVE26 Spastic paraplegia 15 Childhood or early adulthood; median onset of parkinsonism: ~15 (14-30) yrs6 (atypical parkinsonism)Progressive spastic paraparesis, levodopa responsive, MRI abnormalities (thin corpus callosum)

DD = developmental delay; EOPD = early-onset Parkinson disease; ID = intellectual disability; PD = Parkinson disease

1.

Nomenclature based on Marras et al [2016]

2.

Data from MDSGene​.org (accessed 10-10-2023)

3.

Based on persons with clinical information reported in the literature

4.
5.

PARK-PINK1 & PARK-Parkin EOPD are clinically indistinguishable; non-motor manifestations including psychiatric features may be more common in PARK-PINK1 than in PARK-Parkin.

6.

Other features of this disorder typically manifest before the onset of parkinsonism.

From: DNAJC6 Parkinson Disease

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.