BACKGROUND AND PURPOSE: 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.
BACKGROUND AND PURPOSE: 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: Louis R Caplan; Juan Arenillas; Steven C Cramer; Anne Joutel; Eng H Lo; James Meschia; Sean Savitz; Elizabeth Tournier-Lasserve Journal: Arch Neurol Date: 2011-05-09
Authors: Vikas Y Rao; Krishna B Shah; Robert J Bollo; Michel E Mawad; William E Whitehead; Daniel J Curry; Robert C Dauser; Thomas G Luerssen; Andrew Jea Journal: Childs Nerv Syst Date: 2012-09-27 Impact factor: 1.475
Authors: Stéphanie Debette; Barbara Goeggel Simonetti; Sabrina Schilling; Juan José Martin; Manja Kloss; Hakan Sarikaya; Ingrid Hausser; Stefan Engelter; Tiina M Metso; Alessandro Pezzini; Vincent Thijs; Emmanuel Touzé; Stefano Paolucci; Paolo Costa; Maria Sessa; Yves Samson; Yannick Béjot; Ayse Altintas; Antti J Metso; Dominique Hervé; Christoph Lichy; Simon Jung; Urs Fischer; Chantal Lamy; Armin Grau; Hugues Chabriat; Valeria Caso; Philippe A Lyrer; Christian Stapf; Turgut Tatlisumak; Tobias Brandt; Elisabeth Tournier-Lasserve; Dominique P Germain; Michael Frank; Ralf W Baumgartner; Caspar Grond-Ginsbach; Marie-Germaine Bousser; Didier Leys; Jean Dallongeville; Anna Bersano; Marcel Arnold Journal: Neurology Date: 2014-10-29 Impact factor: 9.910
Authors: Caspar Grond-Ginsbach; Tobias Brandt; Manja Kloss; Suna Su Aksay; Philipp Lyrer; Christopher Traenka; Philipp Erhart; Juan Jose Martin; Ayse Altintas; Aksel Siva; Gabriel R de Freitas; Andreas Thie; Jochen Machetanz; Ralf W Baumgartner; Martin Dichgans; Stefan T Engelter Journal: Eur Stroke J Date: 2017-02-09