Detailed Courses and Pathological Findings of Colonic Perforation without Diverticula in Sisters with Musculocontractural Ehlers-Danlos Syndrome Caused by Pathogenic Variant in CHST14 (mcEDS- CHST14)

Abstract

Musculocontractural Ehlers-Danlos syndrome (mcEDS) is a heritable connective tissue disorder characterized by multiple congenital malformations and progressive connective-tissue-fragility-related manifestations in the cutaneous, skeletal, cardiovascular, visceral, ocular, and gastrointestinal systems. It is caused by pathogenic variants in the carbohydrate sulfotransferase 14 gene (mcEDS-CHST14) or in the dermatan sulfate epimerase gene (mcEDS-DSE). As gastrointestinal complications of mcEDS-CHST14, diverticula in the colon, small intestine, or stomach have been reported, which may lead to gastrointestinal perforation, here, we describe sisters with mcEDS-CHST14, who developed colonic perforation with no evidence of diverticula and were successfully treated through surgery (a resection of perforation site and colostomy) and careful postoperative care. A pathological investigation did not show specific abnormalities of the colon at the perforation site. Patients with mcEDS-CHST14 aged from the teens to the 30s should undergo not only abdominal X-ray photography but also abdominal computed tomography when they experience abdominal pain.

Keywords: carbohydrate sulfotransferase 14 (CHST14); diverticulum; gastrointestinal perforation; musculocontractural Ehlers–Danlos syndrome (mcEDS).

Figure 1

Abdominal X-ray photography (Xp) and computed tomography (CT) images at the onset of acute abdomen in Patients 1 (A) and 2 (B). Abdominal Xp in a standing position showed no abnormal findings (A1). Abdominal CT revealed intraperitoneal free air (A2, A3) and findings suggestive of a perforation site (A4). Abdominal Xp in standing (B1) and supine (B2) positions showed no abnormal findings. Abdominal CT revealed a small amount of free air on the surface of the liver (B3) and findings suggestive of a perforation site (B4). Arrowheads indicate free air and arrows indicate a possible perforation site.

Figure 2

Surgical details of Patients 1 (A) and 2 (B). In Patient 1, the perforated site of the colon (A1) was elevated outside the left upper abdominal wall and a colostomy was constructed (A2). In Patient 2, the perforation site of the colon at the splenic flexure was resected using a linear stapler (B1). A colostomy of the transverse and descending colon was created at the left lower abdominal wall (B2). Macroscopic observation showed the perforation site ((B3), arrowhead) and its sectional view ((B4), arrow).

Figure 3

Histopathology of the perforated area of the colon of Patient 2. Loupe images ((A), hematoxylin–eosin staining; (B), immunological staining for desmin). Black bar indicates 5 mm. A medium-magnification image with hematoxylin–eosin staining (C). No morphological abnormalities are detected in the muscle fibers. Black bar indicates 1 mm. A high-magnification image with elastica-Masson staining (D). No abnormalities are detected in the vessel wall near the perforated area. Black bar indicates 500 μm.