title: Familial cervical artery dissections: clinical, morphologic, and genetic studies.
abstract: OBJECTIVE
  Genetic risk factors are thought to play a role in the etiology of spontaneous cervical artery dissections (CAD). However, familial CAD is extremely rare. In this study we analyzed patients with familial CAD and asked the question whether familial CAD has particular features.
  
  
  METHODS
  Seven families with 15 CAD patients were recruited. All patients were carefully investigated by a neurologist, a neuroradiologist, and a dermatologist for clinical characteristics. From 11 patients a skin biopsy was performed to study the morphology of the connective tissue and to analyze the coding sequences of COL3A1, COL5A1, COL5A2, and part of COL1A1.
  
  
  RESULTS
  The mean age of the patients (n=15, 9 women) at their first dissection was 36.2 years (median age 32 years, range 18 to 59). Two patients had bilateral CAD. One patient had a right and a left internal carotid artery dissection in successive weeks, another patient had 5 dissections over a period of 8 years. A high intrafamilial correlation was found between the affected vessels (ie, the carotid and the vertebral arteries) and between ages at the first dissection. In 1 patient we found clear and reproducible ultrastructural abnormalities in the skin biopsy, but the second patient from the family was not studied, because he died as a result of CAD before this study. The dermal connective tissue aberrations in the examined patient were similar to mild findings in patients with vascular Ehlers-Danlos syndrome (EDS type IV), but might be iatrogenic and related to long-term corticosteroid inhalation therapy. All other analyzed patients showed normal connective tissue morphology. In patients from 6 families we analyzed the whole coding sequence of COL3A1, COL5A1, and COL5A2, and from part of COL1A1. A missense mutation in the COL3A1 gene (leading to a G157S substitution in type III procollagen) was detected in both patients from 1e family. Two patients from another family carried a rare nonsynonymous coding polymorphism in COL5A1 (D192N); 1 of them carried also a rare variant in COL5A2 (T12337).
  
  
  CONCLUSIONS
  Familial CAD patients are young and probably are at high risk for recurrent or multiple CAD. Ultrastructural alterations of the dermal connective tissue might not be an important risk factor for familial CAD. However, the finding of a COL3A1 mutation revealed the presence of an inherited connective tissue disorder in 1 family.
authors.affiliation: Department of Neurology, Sanatorio Allende, Hipólito Irigoyen 384, CP 5000, Córdoba, Argentine. juanjmartin@gmx.net
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Martin
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hausser
authors.forename: Philippe
authors.initials: P
authors.lastname: Lyrer
authors.forename: Otto
authors.initials: O
authors.lastname: Busse
authors.forename: Ralf
authors.initials: R
authors.lastname: Schwarz
authors.forename: Rolf
authors.initials: R
authors.lastname: Schneider
authors.forename: Tobias
authors.initials: T
authors.lastname: Brandt
authors.forename: Manja
authors.initials: M
authors.lastname: Kloss
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaninger
authors.forename: Stefan
authors.initials: S
authors.lastname: Engelter
authors.forename: Caspar
authors.initials: C
authors.lastname: Grond-Ginsbach
mesh_terms: D000293:Adolescent; D000328:Adult; D000784:Aortic Dissection / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D002574:Cervical Vertebrae / Q000098:blood supply*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014711:Vertebral Artery / Q000473:pathology*