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FAMILY HISTORY IN YOUNG ONSET PARKINSON'S DISEASE
  1. Naveed Malek,
  2. Nin Bajaj,
  3. Roger Barker,
  4. Yoav Ben–Shlomo,
  5. David Burn,
  6. Thomas Foltynie,
  7. Huw Morris,
  8. Nigel Williams,
  9. Nicholas Wood,
  10. Donald Grosset
  1. Institute of Neurological Sciences, Southern General Hospital; Queen's Medical Centre, Nottingham; Cambridge Centre for Brain Repair, Cambridge; University of Bristol; University of Newcastle; University College London; University Hospital of Wales, Cardiff; MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff; Institute of Neurological Sciences, Southern General Hospital

    Abstract

    Background Young onset Parkinson's disease is more likely to be genetic than older onset Parkinson's disease, particularly with a positive family history, and there are also racial differences.1 2 Both autosomal dominant and recessive causes of Parkinson's disease are described; analysis of family history data is instructive regarding genetic risk and likely inheritance patterns.

    Methods Detailed family histories were obtained from young onset (<50 years old) Parkinson's disease patients by the Parkinson's Repository of Biosamples and Networked Datasets (PRoBaND) clinical consortium.

    Results In 240 cases enrolled, the mean age of onset of Parkinson's disease was 43.6 years (SD 5.8), mean disease duration was 10.2 years (SD 6.8) and 69.3% are male. Most (94.1%) were Caucasian; the largest ethnicity was white British (89.1%); 3.2% were of Asian, and 0.5% of African heritage. There was a family history of Parkinson's disease in one or more first degree relative in 12.5%, one or more second degree relative in 13.3%, and one or more family members had Parkinson's disease in 23.7% of the index cases (Figure). The positive first degree family history was parental in 10.8% of patients, in one or more siblings in 2.5% of cases, and one or more children in <0.5% of cases. 5.8% had a maternal grandparent, and 2.9% had a paternal grandparent with PD.

    Conclusion Positive family histories in about a quarter of young onset PD patients is similar to previous studies.3 Around one tenth of patients in this population may have autosomal dominant inheritance. Far fewer have a family history pattern suggesting autosomal recessive inheritance, but this may be underestimated from family tree assessment. Genetic testing is now underway in our cohort, both for known genes including GBA, LRRK2, PARKIN, PINK1, and SNCA, but also for the analysis of genetic variation (single nucleotide polymorphism) that may be of greater significance to the presence and severity of disease–related complications, such as cognitive impairment and therapy responses.

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