This is the first report of mutation in the C-terminal domain of Synaptojanin 1 protein causing mild juvenile PD with generalized seizures, cognitive impairment, and good respond to levodopa treatment.
Mutations in the SYNJ1 gene have been associated with early-onset of atypical Parkinson's disease or severe neurodegeneration with intractable seizures.
Genetic atypical Parkinson's disease (PD) describes monogenic forms of PD that resemble idiopathic PD but feature prominent atypical clinical signs and symptoms and can be sub-grouped into i) atypical monogenic forms caused by mutations in the ATP13A2, DNAJC6, FBXO7, SYNJ1, VPS13C, and DCTN genes; ii) monogenic PD more closely resembling idiopathic PD, but associated with atypical features in at least a subset of cases (SNCA-, LRRK2-, VPS35-, Parkin-, PINK1-, and DJ-1-linked PD; iii) carriers of mutations in genes that are usually associated with other movement disorders but may present with parkinsonism, such as dopa-responsive dystonia.