RT Book, Section
A1 Shuch, Brian
A1 Linehan, W. Marston
A2 Murray, Michael F.
A2 Babyatsky, Mark W.
A2 Giovanni, Monica A.
A2 Alkuraya, Fowzan S.
A2 Stewart, Douglas R.
SR Print(0)
ID 1102705191
T1 von Hippel-Lindau Syndrome
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=1102705191
RD 2024/04/19
AB Disease  summary:Manifestations  of  von  Hippel-Lindau  (VHL)  disease  were  first  observed  in  the  early  20th  century  by  Drs.  von  Hippel  (retinal  angiomas)  and  Lindau  (cerebellar  hemangioblastomas).The  disease  is  characterized  by  the  development  of  multiple  tumors  including  retinal  angiomas,  central  nervous  system  (CNS)  hemangioblastomas,  pancreatic  cysts  and  neuroendocrine  tumors,  renal  cell  carcinomas  (RCC),  pheochromocytomas,  and  epididymal  cystadenomas.Prior  to  comprehensive  screening  and  early  intervention,  median  survival  of  those  with  VHL  was  less  than  50  years  due  to  complications  of  RCC  and  hemangioblastomas.VHL  has  an  incidence  of  1:35,000  and  the  majority  of  affected  individuals  have  a  family  history  of  the  disease.Patients  can  have  a  germline  missense,  nonsense,  or  partial/complete  deletion  of  the  VHL  gene.  Most  tumors  generally  have  a  second  hit  in  the  wild-type  allele,  which  results  from  loss  of  heterozygosity,  hypermethylation,  and  occasionally  a  second  mutation.Hereditary  basis:VHL  is  a  highly  penetrant  autosomal  dominant  disease  due  to  a  germline  mutation  in  the  VHL  gene.  Children  of  affected  individuals  have  a  50%  chance  of  inheriting  the  affected  allele.  In  kindreds  with  VHL,  up  to  a  quarter  have  no  family  history  and  have  been  considered  as  founder  mutations.  However  in  cases  of  apparently  de  novo  mutations,  these  actually  may  represent  a  nontraditional  transmission  of  the  VHL  mutation.  Detailed  testing  of  parents  of  affected  individuals  can  demonstrate  genetic  mosaicism  in  VHL.Differential  diagnosis:It  is  important  to  distinguish  VHL  from  other  multiorgan  syndromes  that  have  overlapping  tumor  types.  Syndromes  that  feature  pheochromocytomas  include  multiple  endocrine  neoplasia  (MEN2a/b),  neurofibromatosis  type  1,  and  succinate  dehydrogenase  deficiency  (SDH).  Other  kidney  cancer  syndromes  associated  with  multiple  tumor  types  include  Birt-Hogg-Dubé  (BHD),  hereditary  leiomyomatosis  and  renal  cell  carcinoma  (HLRCC),  SDH  B  and  C  deficiency,  and  Cowden  syndrome.