Biallelic SYNJ1 Variants in a patient with multiple system atrophy mimic syndrome

SYNJ1 (biallelic variants, compound heterozygous)

Biallelic loss of function of SYNJ1 (synaptojanin-1, phosphoinositide phosphatase) → defective synaptic vesicle recycling and autophagy; previously associated with early-onset Parkinson disease (PARK20), now expanded to late-onset MSA-like phenotype

Description of a 71-year-old patient with progressive motor and autonomic deterioration mimicking multiple system atrophy (MSA), in whom genotyping reveals biallelic SYNJ1 variants. SYNJ1, previously identified in early-onset Parkinson disease (PARK20), encodes synaptojanin-1, a phosphoinositide phosphatase essential for synaptic vesicle recycling. Functional studies confirm the pathogenic impact. This case substantially expands the phenotypic spectrum of SYNJ1 toward a late-onset MSA-like phenotype.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Biallelic SYNJ1 is emerging as a genetic cause of atypical parkinsonian syndromes beyond early Parkinson disease. Include SYNJ1 in genetic panels for MSA-like presentations, particularly in patients of consanguineous ancestry. The diagnostic impact is amplified by the absence of a specific MSA biomarker.

major phenotypic expansion (MSA-like) +2; biallelic + functional studies +2; diagnostic impact (MSA vs genetic differential) +2; Neurol Sci +1