RT Book, Section
A1 Mastrianni, James
A2 Murray, Michael F.
A2 Babyatsky, Mark W.
A2 Giovanni, Monica A.
A2 Alkuraya, Fowzan S.
A2 Stewart, Douglas R.
SR Print(0)
ID 1102705395
T1 Genetic Prion 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 accessmedicine.mhmedical.com/content.aspx?aid=1102705395
RD 2024/04/19
AB Disease  summary:Rare  neurodegenerative  diseases  typically  associated  with  rapidly  progressive  dementia  and  ataxia.Disease  subtypes—Sporadic  (s)  and  familial  (f)  forms  of  Creutzfeldt-Jakob  disease  (sCJD  and  fCJD)  and  fatal  insomnia  (sFI  and  fFI).  Gerstmann-Sträussler-Scheinker  disease  (GSS)  is  always  genetic.  Rarer  forms  caused  by  exposure  to  prions,  include  variant  CJD  (vCJD)  and  kuru.  A  new  phenotype,  labeled  Variably  Protease-Sensitive  Prionopathy,  has  recently  been  recognized  in  a  small  number  of  patients.Transmissible  properties—Prions  are  misfolded  isoforms  of  prion  protein  (PrP)  that  can  interact  with  and  convert  normal  prion  protein  (PrPC)  to  the  misfolded  pathogenic  isoform  (PrPSc).  Nervous  tissues  from  affected  patients  with  any  subtype  of  prion  disease  can  potentially  transfer  disease  to  healthy  individuals,  if  directly  introduced.Diagnostic  tests—For  sCJD,  brain  magnetic  resonance  imaging  (MRI)  diffusion-weighted  imaging  (DWI)  sequences  often  show  hyperintensity  of  the  cortical  ribbon  or  basal  ganglia,  and  electroencephalography  (EEG)  may  demonstrate  periodic  sharp  waves  complexes  of  approximately  1  per  second.  Cerebrospinal  fluid  (CSF)  may  show  elevation  of  14-3-3  and/or  extremely  elevated  tau  protein.  In  FI,  positron  emission  tomography  (PET)  scan  of  brain  shows  a  hypometabolic  thalamus.  Genetic  testing  assists  with  diagnosis  of  familial  forms  of  prion  disease.Hereditary  basis:About  10%  to  15%  of  all  cases  result  from  an  autosomal  dominant  mutation  of  the  PrP  gene  (PRNP).  Homozygosity  at  the  common  polymorphic  codon  129  of  PRNP  is  more  common  in  cases  of  sCJD  and  vCJD.  Codon  129  genotype  may  influence  the  phenotype  of  some  genetic  prion  diseases.  No  other  genes  are  directly  causal.Differential  diagnosis:Other  neurodegenerative  conditions,  including  Alzheimer  disease,  Huntington  disease,  frontotemporal  lobar  dementias,  spinocerebellar  ataxia,  and  dementia  with  Lewy  bodies,  among  others.  CNS  viral  and  bacterial  infections,  paraneoplastic  syndromes,  Hashimoto  encephalopathy,  and  Whipple  disease  are  important  considerations  in  the  workup.