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Type IV Ehlers-Danlos syndrome: a surgical emergency

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Q1: What is seen on the chest radiograph?

The chest radiograph (see p502) shows gas under the right hemidiaphragm. This is not free intraperitoneal gas, but is a loop of bowel interposed between the liver and the right hemidiaphragm, the Chilaiditi sign.1

Q2: Comment on the history and computed tomogram

There was no evidence of perforative peritonitis. The computed tomogram (see p502) shows a large retroperitoneal haematoma around the aorta, but no aortic aneurysm. Spontaneous retroperitoneal bleeding is often associated with type IV Ehlers-Danlos syndrome and is the commonest cause of death in this population.

Discussion

Ehlers-Danlos syndrome is an inherited disorder of collagen synthesis. Type IV, far less common than types I, II and III, is caused by a deficiency of type III collagen.2 The causative mutations in the COL3A1 gene are very variable, and are usually inherited in an autosomal dominant pattern. Biochemical examination in the present case showed the secretion of an abnormal type III collagen protein.3 DNA sequencing of cDNA produced from cultured skin fibroblasts showed a glycine (GGA) to glutamic acid (GAA) substitution at position 847 of the COL3A1 gene (fig 1). In keeping with other helical glycine substitutions, this causes severe reduction of tissue type III collagen, resulting in severely weakened arteries, intestines, ligaments, and other organs. We also detected similar changes in his mother and brother, while his maternal grandmother was a clinically silent somatic/gonadal mosaic for the error.3

Figure 1

Sequencing of DNA from patient’s cultured skin fibroblasts (reproduced from Human Genetics 1992;89:414–18, with permission from Springer Verlag, Berlin).

Type III collagen forms only 15% of normal skin and ligaments, and is absent in bones and joints. In contrast to the other Ehlers-Danlos syndrome subtypes, skin laxity and joint hypermotility are not prominent features of type IV Ehlers-Danlos syndrome. The walls of blood vessels, the gastrointestinal tract and uterus are the main depots of type III collagen. These patients often suffer spontaneous rupture of arteries, commonly affecting main branches of the aorta, but not uncommonly involving intrathoracic and intracerebral vessels.4 Haemorrhage may occur even in the absence of aneurysmal dilatation of the vessel. Spontaneous retroperitoneal bleeds are the commonest cause of death in this population. They are also at risk of spontaneous perforations of the gastrointestinal tract, commonly the colon.5 During the third trimester of pregnancy, there is a 5%–15% risk of uterine rupture.6

The present case demonstrates most of the complications that are associated with this unfortunate condition. It is due to a high incidence of these catastrophic complications that the life expectancy of patients with type IV Ehlers-Danlos syndrome is markedly shortened. They usually die in the fourth decade of life and survival beyond the age of 50 is rare. This contrasts with other Ehlers-Danlos syndrome variants who have normal life expectancy.

Awareness and early recognition of these life threatening complications are essential to the management of this unfortunate group of patients. Elective surgery should be undertaken with great caution, and only if absolutely necessary, as they tend to bleed uncontrollably and heal poorly after operations.

Final diagnosis

Spontaneous retroperitoneal bleeding associated with type IV Ehlers-Danlos syndrome.

References

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