9 December 2009 - Case of the Week #163


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Thanks to Dr. Kim Billingham, Great Western Hospital, Swindon, UK, for contributing this case and much of the discussion. To contribute a Case of the Week, follow the guidelines on our Case of the Week page.



Case of the Week #163


Clinical History


A 9 year old boy presented with a five day history of lower abdominal pain and nausea.There was no history of trauma.Laparotomy showed a perforated sigmoid colon and faecal peritonitis. His past medical history was significant for bilateral herniotomies as an infant.


Nine years previously, the pathology lab received a right hemicolectomy specimen from the boyís mother, after her caecum perforated during a caesarean section.


Sections from the sigmoid colon of the 9 year old boy were obtained:


Micro images:


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What is your diagnosis?




























Ehlers-Danlos syndrome, vascular type (type IV)




The sigmoid colon included a 2 mm focus of full thickness perforation.Serial sectioning showed additional areas of mucosal ulceration, with the bowel wall thickness varying from 1 to 3 mm.The histology showed areas of "punched out" mucosal necrosis, with underlying segmental absence of the muscularis propria. It was replaced by a cellular, reactive fibroblastic proliferation, accompanied by prominent eosinophils. These areas were present in several segments along the circumference of the bowel wall and in various locations along the length of the sigmoid colon.Evidence of peritonitis was also present. No vasculitis, inflammatory bowel disease or diverticuli were noted.


The slides from the motherís prior hemicolectomy had features similar to those in her sonís specimen.Genetic testing of the mother showed she was markedly deficient in collagen type 3, with a mutation of one of her two COL3A1 genes.


Ehlers-Danlos syndrome (EDS) is an inherited heterogenous group of connective tissue disorders characterized by abnormal collagen synthesis (eMedicine, Wikipedia). Six variants of EDS have been described, based on clinical and molecular features (Am J Med Genet 1998;77:31). Clinical symptoms vary by clinical variant, and include skin hyperextensibility and fragility/poor healing; joint hyperextensibility with a propensity to dislocation; eye symptoms with corneal rupture and retinal detachment; kyphoscoliosis and rupture of the colon and large arteries.


Vascular type EDS (type IV - autosomal dominant inheritance) is caused by a mutation in the COL3A1 gene (J Nippon Med Sch 2008;75:254), and is associated with a reduced median survival of only 48 years. There are three distinct types of mutations, which affect either the rate of synthesis, the secretion of type III procollagen or result in structurally abnormal type III collagen. Neonates have an increased incidence of clubfoot and hip dislocation, and rarely have subarachnoid hemorrhage (Am J Clin Pathol 1990;93;579).In children, inguinal hernia, pneumothorax and recurrent joint dislocation or subluxation are common. The skin is translucent with visible veins and is easily bruised. Distinctive facial features are often present, including protruding eyes, a thin nose and lips, sunken cheeks and a small chin. Blood vessels and intestines are typically rich in type III collagen, and adult patients often present with vascular rupture/dissection or gastrointestinal perforation. Uterine rupture may occur during pregnancy, particularly at delivery.


Although there is no specific treatment for EDS, preventative measures are recommended, and there may be a role for high dose Vitamin C.


Additional comment from author: The areas of mucosal necrosis, not shown in the pictures submitted, were all overlying areas in which the muscularis propria was absent (this is illustrated in the pictures submitted), and one of these areas formed the site of the perforation. Perforations are often multiple in these patients (most frequently occurring in the sigmoid colon) and the changes in the colon in this case ranged from defects in the muscularis propria to defects in the muscularis propria and mucosa to the area of perforation.The colon, uterus and blood vessel walls are all rich in type III collagen, and patients with Ehlers-Danlos syndrome (type IV) have quantitative or qualitative defects in their type III collagen, leading to areas of structural weakness in these organs.This predisposes them to spontaneous gastrointestinal perforation, vascular dissection and uterine rupture in pregnancy.



Additional references:Arch Pathol Lab Med 1993;117:989, J Clin Neuromuscular Dis 2009;11:81, Intern Med 2009;48:717


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