ReviewVascular Ehlers–Danlos syndrome
Introduction
Ehlers–Danlos syndrome (EDS) is a heterogeneous group of heritable disorders of connective tissue, characterized by skin hyperextensibility, joint hypermobility and tissue fragility [39], [43]. A revised classification has been proposed following elucidation of the biochemical and molecular basis for several subtypes [4]. Vascular EDS (OMIM 130050, also known as EDS type IV or Sack-Barabas syndrome), is of particular importance as this is the only form associated with a high risk of early death due to arterial, intestinal and uterine ruptures [31].
Section snippets
Facial dysmorphism
The distinctive facial features include a pinched nose, prominent staring eyes with periorbital pigmentation and fine telangiectasae of the eyelids [13], high cheek bones and sunken cheeks, thin lips and lobeless ears. However, facial dysmorphism is absent in some cases of vascular EDS and this can be misleading.
Dermatological manifestations
The earliest clinical manifestations of vascular EDS tend to be cutaneous. Patients bruise easily (Fig. 1) despite normal coagulation studies and, in infants, this can lead to
Laboratory diagnosis
Type III collagen is a fibril forming collagen expressed in early embryos and throughout embryogenesis. In the adult, type III collagen is a major component of the extracellular matrix in a variety of internal organs and in the skin. Type III collagen is a homotrimer formed by the association of three α1(III) chains. The core of the molecule is a triple helix with an amino acid sequence characterized by Gly-X-Y repeats. To ensure proper assembly of the α monomers, the Gly-X-Y repeats must
Genetic counseling
EDS type IV is a monogenic orphan disease transmitted as an autosomal dominant trait (OMIM 130050). Affected individuals have a 50% chance of passing on the mutated gene to each child. The incidence of de novo mutations is high and sporadic cases account for half of reported cases. Somatic and germ-line mosaicism has been reported [26], [34]. Until the 11th edition of the catalogue of monogenic inherited diseases [24], recessive autosomal transmission of vascular EDS was also considered a
Conclusion
Vascular EDS is a distinct form of EDS. Diagnosis is based initially on clinical findings and is easiest for patients presenting with acrogeria or a first complication. Biological or molecular assays of collagen III can be very helpful in confirming the diagnosis. There are currently no specific treatments, and medical intervention is limited to symptomatic treatment, precautionary measures and genetic counseling. After diagnosis, a specialist in medical genetics should be consulted and
References (44)
- et al.
Emergency repair of type A aortic dissection in type IV Ehlers–Danlos syndrome
Cardiovasc. Surg.
(2000) Ehlers–Danlos syndrome type IV: a genetic disorder in many guises
J. Invest. Dermatol.
(1995)- et al.
Spontaneous coronary artery rupture and cardiac tamponade in Ehlers–Danlos syndrome type IV
Int. J. Cardiol.
(1996) Clinical and genetic features of vascular Ehlers–Danlos syndrome
Ann. Vasc. Surg.
(2002)- et al.
Emergency operation for thoracic aortic aneurysm caused by the Ehlers–Danlos syndrome
Ann. Thorac. Surg.
(1994) - et al.
Intracranial aneurysms in Ehlers–Danlos syndrome type IV in early childhood
Pediatr. Neurol.
(2001) - et al.
Presentation of Ehlers–Danlos syndrome: iliac artery pseudoaneurysm rupture
Ann. Emerg. Med.
(1996) - et al.
Haploinsufficiency for one COL3A1 allele of type III procollagen results in a phenotype similar to the vascular form of Ehlers–Danlos syndrome, Ehlers–Danlos syndrome type IV
Am. J. Hum. Genet.
(2001) Ehlers–Danlos syndrome type IV: dramatic, deceptive, and deadly
Am. J. Surg.
(1984)- et al.
Ehlers–Danlos syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability, and processing of type III procollagen
J. Biol. Chem.
(1988)
Fatal vascular catastrophe in Ehlers–Danlos syndrome: a case report and review
J. Emerg. Med.
Fatal hemoptysis in Ehlers–Danlos syndrome. Old malady with a new curse
Chest
Structure of cDNA clones coding for the entire preproa1(III) chain of human type III collagen
Biochem. J.
Myocardial infarction and coronary artery dissection during pregnancy associated with type IV Ehlers–Danlos syndrome
Am. J. Perinatol.
Ehlers–Danlos syndromes: revised nosology, Villefranche, 1997
Am. J. Med. Genet.
Surgical pitfalls in a patient with type IV Ehlers–Danlos syndrome and spontaneous colonic rupture. Report of a case
Dis. Colon Rectum
Multiple vascular and bowel ruptures in an adolescent male with sporadic Ehlers–Danlos syndrome type IV
Pediatr. Dev. Pathol.
The Ehlers–Danlos syndrome: a heritable collagen disorder as cause of bleeding
Thromb. Haemost.
Human α1(III) and α 2(V) procollagen genes are located on the long arm of chromosome 2
Proc. Natl. Acad. Sci. USA
Spontaneous rupture of liver in a patient with Ehlers Danlos disease type IV
Dig. Dis. Sci.
Ehlers–Danlos syndromes. Clinical, genetic and molecular aspects
Ann. Dermatol. Venereol.
Large kindred with Ehlers–Danlos syndrome type IV due to a point mutation (G571S) in the COL3A1 gene of type III procollagen: low risk of pregnancy complications and unexpected longevity in some affected relatives
Am. J. Med. Genet.
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