Van Duijn et al. (2001) reported a consanguineous family from a genetically isolated community in the southwestern region of the Netherlands in which 4 individuals had a form of early-onset Parkinson disease. Onset of symptoms was before the ... Van Duijn et al. (2001) reported a consanguineous family from a genetically isolated community in the southwestern region of the Netherlands in which 4 individuals had a form of early-onset Parkinson disease. Onset of symptoms was before the age of 40 years with resting tremor, postural tremor, bradykinesia, loss of postural reflexes, and an asymmetric onset of symptoms. Three of the 4 patients also showed psychiatric symptoms, including psychotic episodes. In all patients, the progression of disease was slow, and there were no atypical features or signs of involvement of additional neurologic systems. Abou-Sleiman et al. (2003) reported 2 unrelated patients with early-onset Parkinson disease. They presented at ages 36 and 39 years with rigidity, bradykinesia, and tremor, with a good response to L-dopa therapy. Both patients had psychologic disturbances early in the disease, particularly an anxiety disorder. - Clinical Variability Annesi et al. (2005) reported 3 affected sibs from a consanguineous southern Italian family in which 3 sibs had early-onset parkinsonism at ages 36, 35, and 24 years, respectively. One sib also had features of amyotrophic lateral sclerosis with upper and lower limb weakness, fasciculations, and EMG evidence of denervation. He later developed severe, bulbar involvement, muscle atrophy, and hyperreflexia with extensor plantar responses, as well as marked cognitive impairment and parkinsonism. He died from respiratory failure at age 43 years. The other 2 sibs had prominent parkinsonism, hyperreflexia, urinary incontinence, and behavioral abnormalities, such as aggression and bulimia. Annesi et al. (2005) noted that the phenotype was reminiscent of that reported in Guam (105500).
In the family reported by van Duijn et al. (2001) and in 1 of the families reported by Bonifati et al. (2002), Bonifati et al. (2003) identified mutations in the DJ1 gene that cosegregated with the disease (602533.0001-602533.0002). ... In the family reported by van Duijn et al. (2001) and in 1 of the families reported by Bonifati et al. (2002), Bonifati et al. (2003) identified mutations in the DJ1 gene that cosegregated with the disease (602533.0001-602533.0002). Among 185 unrelated patients with early-onset Parkinson disease, Abou-Sleiman et al. (2003) identified 2 patients with mutations in the DJ1 gene (602533.0003-602533.0004). The authors estimated that the frequency of DJ1 mutations in early-onset Parkinson disease is very low, at approximately 1%. Among 118 familial patients and 7 sporadic patients with early-onset Parkinson disease (range of age at onset, 12 to 78 years), Ibanez et al. (2003) did not identify any mutations in the DJ1 gene, suggesting that PARK7 is not a common locus for early-onset autosomal recessive Parkinson disease. The patients came from Europe, South America, Lebanon, Asia, Turkey, and North Africa. In 3 affected sibs from a consanguineous southern Italian family with early-onset parkinsonism, amyotrophic lateral sclerosis, and cognitive impairment, Annesi et al. (2005) identified double homozygosity for 2 mutations in the DJ1 gene (602533.0006). Alcalay et al. (2010) identified a mutation in the DJ1 gene in 1 (0.2%) of 953 patients with early-onset PD before age 51, including 77 and 139 individuals of Hispanic and Jewish ancestry, respectively.