RT Book, Section
A1 Hardy, John
A2 Murray, Michael F.
A2 Babyatsky, Mark W.
A2 Giovanni, Monica A.
A2 Alkuraya, Fowzan S.
A2 Stewart, Douglas R.
SR Print(0)
ID 1102705046
T1 Parkinson Disease
T2 Clinical Genomics: Practical Applications in Adult Patient Care
YR 2014
FD 2014
PB McGraw-Hill Education
PP New York, NY
SN 9780071622448
LK accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102705046
RD 2024/04/24
AB Disease  summary:Parkinson  disease  (PD)  is  marked  by  tremor,  muscle  rigidity,  and  slowed  movement  and  known  to  have  multiple  etiologies  both  genetic  and  idiopathic.  Many  genetic  risk  factors  are  known  but  environmental  factors  are  not  established.A  cardinal  pathologic  feature  is  the  presence  of  Lewy  bodies  in  the  substantia  nigra,  although  a  minority  of  cases  may  not  exhibit  this  finding.The  disease  presents  with  bradykinesia  and  often  with  a  resting  tremor.  At  first  the  disease  responds  well  to  l-dopa  and  related  therapies,  but  as  the  disease  progresses,  therapy  becomes  more  problematic  with  shorter  periods  of  drug  efficacy  and  dyskinesias  as  an  effect  of  treatment.  Cognitive  and  other  complications  increase  during  the  disease  progression.Anatomic  involvement:  While  the  major  motor  symptoms  of  the  disease  result  from  the  damage  to  the  substantia  nigra,  recent  studies  from  Braak  have  suggested  that  the  disease  may  start  in  the  lower  brain  stem  and  spread  progressively.Differential  diagnosis:It  includes  progressive  supranuclear  palsy,  multiple  system  atrophy,  and  essential  tremor.Monogenic  forms:Many  monogenic  forms  exist,  both  recessive  and  dominant;  see  Table  126-1.Family  history:An  affected  first-degree  relative  confers  an  increase  in  risk  of  disease,  but  this  varies  both  with  age,  and  naturally  is  dependent  on  the  precise  etiology  in  any  family.Twin  studies:Monozygotic  twins  have  a  20%  to  50%  concordance  rate  in  PD,  lower  in  dizygotic  twins.  Since  this  is  a  late-onset  disease  and  a  disease  in  which  the  onset  in  twin  can  vary  enormously,  precise  figures  are  not  available  and  are,  in  any  event,  difficult  to  interpret.Environmental  factors:None  are  known,  although  smoking  and  caffeine  intake  are  negatively  associated  with  disease  occurrence.  Whether  this  relates  to  the  role  of  dopamine  in  the  reward  system  and  therefore  is  related  to  premorbid  addictive  behavior  is  not  clear.  MPTP  (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)  is  a  neurotoxin  which  causes  permanent  symptoms  of  PD  and  has  been  used  to  study  disease  models  in  various  animal  studies;  MPTP  has  caused  human  cases  when  injected  but  has  no  association  with  typical  disease  presentations.Genome-wide  associations:Many  associations  exist.  Disease-associated  genetic  variants  (single-nucleotide  polymorphisms  [SNPs])  provide  insight  into  disease  pathogenesis;  testing  for  SNPs  is  not  yet  clinically  validated  to  diagnose  or  guide  management  of  PD  (Table  126-2).