title: Frequency and phenotypes of cutaneous vascular malformations in a consecutive series of 417 patients with familial cerebral cavernous malformations.
abstract: BACKGROUND
  Familial cerebral cavernous malformations (FCCM) are vascular malformations inherited as an autosomal-dominant condition. Three genes (KRIT1/CCM1, MGC4607/CCM2, PDCD10/CCM3) have been identified so far. Extra-neurological manifestations include retinal and cutaneous vascular malformations. The cutaneous vascular malformation, which had been more specifically associated with FCCM, is hyperkeratotic cutaneous capillary venous malformation (HCCVM).
  
  
  OBJECTIVE
  To define the frequency of cutaneous vascular malformations in patients with FCCM, to precise their different phenotypes, and to study the association of each cutaneous vascular malformation subtype with the different three mutated CCM genes.
  
  
  METHODS
  Dermatological inquiry was systematically performed in a large series of consecutive FCCM patients. Cutaneous biopsies were reviewed when available. Cutaneous vascular malformations classification was based on predominant anomalous channels, using the current International Society for the Study of Vascular Anomalies classification. Molecular screening of CCM genes was performed. Results Four hundred seventeen consecutive FCCM patients from 182 unrelated families were included. 38 patients (9%) from 25 different families had cutaneous vascular malformations. In these 38 patients, cutaneous vascular malformations were classified as follows: 13 capillary malformations (CM), 15 HCCVM, 8 venous malformations (VM) and 2 unclassified lesions. All patients (92%), but one with CM had a KRIT1/CCM1 mutation. The last patient had no detectable mutation. All of the 15 patients with HCCVM had a KRIT1/CCM1 mutation; 86.7% of cutaneous vascular malformation patients (33 of 38) had a KRIT1/CCM1 mutation.
  
  
  CONCLUSIONS
  Cutaneous vascular malformations are seen in 9% of FCCM patients. Three distinct major cutaneous vascular malformations phenotypes were identified: HCCVM (39%), CM (34%) and VM (21%). CCM1 is the most frequently mutated gene in cutaneous vascular malformations-FCCM patients.
authors.affiliation: Department of Neurology. CHU Caremeau, Nîmes, France.
authors.forename: J
authors.initials: J
authors.lastname: Sirvente
authors.forename: O
authors.initials: O
authors.lastname: Enjolras
authors.forename: M
authors.initials: M
authors.lastname: Wassef
authors.forename: E
authors.initials: E
authors.lastname: Tournier-Lasserve
authors.forename: P
authors.initials: P
authors.lastname: Labauge
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001706:Biopsy; D002352:Carrier Proteins / Q000235:genetics; D020785:Central Nervous System Vascular Malformations / Q000150:complications*; D006801:Humans; D000075927:KRIT1 Protein; D008565:Membrane Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D015995:Prevalence; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012189:Retrospective Studies; D012867:Skin / Q000098:blood supply / Q000473:pathology; D017445:Skin Diseases, Vascular / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D054079:Vascular Malformations / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*
chemical_list: D051017:Apoptosis Regulatory Proteins; C502544:CCM2 protein, human; D002352:Carrier Proteins; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C495390:PDCD10 protein, human; D011518:Proto-Oncogene Proteins