Parkinson disease-19 is an autosomal recessive neurodegenerative disorder characterized by onset of parkinsonism in the first or second decade. Some patients may have additional neurologic features, including mental retardation and seizures (summary by Edvardson et al., 2012 and ... Parkinson disease-19 is an autosomal recessive neurodegenerative disorder characterized by onset of parkinsonism in the first or second decade. Some patients may have additional neurologic features, including mental retardation and seizures (summary by Edvardson et al., 2012 and Koroglu et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease, see PD (168600).
Edvardson et al. (2012) reported 2 brothers, born of Arab-Muslim parents of Palestinian origin, with juvenile-onset Parkinson disease. Both had normal early psychomotor development, but showed motor symptoms consistent with Parkinson disease at ages 11 and 7, respectively. ... Edvardson et al. (2012) reported 2 brothers, born of Arab-Muslim parents of Palestinian origin, with juvenile-onset Parkinson disease. Both had normal early psychomotor development, but showed motor symptoms consistent with Parkinson disease at ages 11 and 7, respectively. Features included bradykinesia, rigidity, postural instability, hypomimia, dysarthria, and asymmetric resting tremor. L-DOPA treatment was ineffective, and 1 patient became wheelchair-bound at age 13. The second patient had a more insidious disease course, and was dependent with an inability to walk by age 18. One patient had hypometric saccades. Brain MRI in both patients was unremarkable. Cognition was intact. Koroglu et al. (2013) reported 4 patients from a large consanguineous Turkish family with juvenile-onset, rapidly progressive parkinsonism and mild to moderate mental retardation. The patients had onset of tremor and bradykinesia at 10 to 11 years of age. Other features included postural instability, rigidity, intermittent dystonic symptoms, hypomimia, and pyramidal signs. Three patients had absence and generalized seizures that started at ages 1 to 5 years and were well controlled. Response to L-DOPA was good, but limited by severe side effects. Later features included dysarthria, anarthria, and akinesia. All were wheelchair-bound or bedridden 10 to 15 years after onset. Brain MRI was unremarkable except in 1 patient who had diffuse brain atrophy.
In 2 brothers, born of consanguineous Palestinian parents, with juvenile-onset Parkinson disease, Edvardson et al. (2012) identified a homozygous loss-of-function mutation in the DNAJC6 gene (608375.0001). The mutation was found by homozygosity mapping combined with whole-exome sequencing. Because ... In 2 brothers, born of consanguineous Palestinian parents, with juvenile-onset Parkinson disease, Edvardson et al. (2012) identified a homozygous loss-of-function mutation in the DNAJC6 gene (608375.0001). The mutation was found by homozygosity mapping combined with whole-exome sequencing. Because the DNAJC6 gene plays a role in clathrin-mediated endocytosis, the findings suggested that a defect in the neuronal endocytic/lysosomal pathway contributes to the pathogenesis of Parkinson disease. Koroglu et al. (2013) identified a homozygous loss-of-function mutation in the DNAJC6 gene (608375.0002) in affected members of a consanguineous Turkish family with severe juvenile-onset Parkinson disease and mental retardation. The mutation was found by homozygosity mapping and whole-exome sequencing.