Parkinson disease-20 is an autosomal recessive neurodegenerative disorder characterized by young adult-onset of parkinsonism. Additional features may include seizures, cognitive decline, abnormal eye movements, and dystonia (summary by Krebs et al., 2013 and Quadri et al., 2013). ... Parkinson disease-20 is an autosomal recessive neurodegenerative disorder characterized by young adult-onset of parkinsonism. Additional features may include seizures, cognitive decline, abnormal eye movements, and dystonia (summary by Krebs et al., 2013 and Quadri et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease, see PD (168600).
Krebs et al. (2013) reported 2 Iranian sibs, born of consanguineous parents, with early-onset Parkinson disease. Both patients had onset of generalized tonic-clonic seizures in early childhood; the seizures were well controlled with phenobarbital, and both patients showed ... Krebs et al. (2013) reported 2 Iranian sibs, born of consanguineous parents, with early-onset Parkinson disease. Both patients had onset of generalized tonic-clonic seizures in early childhood; the seizures were well controlled with phenobarbital, and both patients showed normal psychomotor development. In their early twenties, both patients developed progressive parkinsonism manifest as bradykinesia, rigidity, tremor, shuffling gait, postural instability, apraxia of eyelid opening, and dysarthria. Treatment with L-DOPA was effective, but both patients developed secondary dyskinesias. Brain MRI of 1 patient showed mild cortical atrophy and T2-weighted hyperintensities in the white matter, mainly posteriorly. Cognition, cerebellar function, muscle strength, sensation, and autonomic function were normal. Quadri et al. (2013) reported 2 Italian sibs, born of consanguineous parents who originated from Sicily, with early-onset atypical Parkinson disease. Both patients developed a progressive movement disorder in their twenties, with bradykinesia, gait impairment, involuntary movements, dysarthria, and postural instability. Other features included rigidity, tremor, dystonia, staring gaze, supranuclear gaze palsy, and eyelid apraxia. L-DOPA treatment resulted in dyskinesias. Both patients also showed cognitive decline, which was severe in 1. Both patients were severely impaired in their thirties and forties. Brain MRI showed diffuse cerebral cortical atrophy, and SPECT imaging of 1 patient showed a marked decrease in dopamine transporter density in the striatum.
Independently and simultaneously, Krebs et al. (2013) and Quadri et al. (2013) identified the same homozygous missense mutation in the SYNJ1 gene (R258Q; 604297.0001) in affected sibs with autosomal recessive early-onset Parkinson disease from an Iranian and an ... Independently and simultaneously, Krebs et al. (2013) and Quadri et al. (2013) identified the same homozygous missense mutation in the SYNJ1 gene (R258Q; 604297.0001) in affected sibs with autosomal recessive early-onset Parkinson disease from an Iranian and an Italian consanguineous family, respectively. The mutations were found by homozygosity mapping combined with whole-exome sequencing and segregated with the disorder in both families. In vitro functional expression studies by Krebs et al. (2013) indicated that the mutant protein had impaired phosphatase activity of SYNJ1 against its Sac1 domain substrates (PI3P and PI4P). Krebs et al. (2013) did not find SYNJ1 mutations in 20 additional DNA samples from patients with early-onset Parkinson disease, and Quadri et al. (2013) did not find clearly pathogenic biallelic SYNJ1 mutations in 118 unrelated patients with early-onset Parkinson disease. The findings of both Krebs et al. (2013) and Quadri et al. (2013) suggested that defective synaptic vesicle recycling or trafficking may play a role in the neurodegeneration observed in Parkinson disease.