Trust Your Instinct—Lower Intestinal Bleeding Caused by Ehlers-Danlos-Syndrome

**Background:** Gastrointestinal bleeding (GIB) in children is common, but significant acute GIB with hemoglobin drop or cardiocirculatory impairment is rare, warranting hospital admission in only 5% to 10% of cases. About one-third of children have lower GIB. While most causes are benign (e.g., anal fissures related to constipation), life-threatening conditions such as Meckel's diverticulum, severe ulcerative colitis, or intestinal obstruction must be considered. Ehlers-Danlos syndrome (EDS) is a group of connective tissue disorders; vascular EDS (type IV) is a rare form characterized by aneurysms, arterial dissection/rupture, and bowel rupture, associated with pathogenic variants of the COL3A1 gene encoding type III procollagen. Gastrointestinal complications in EDS type IV typically occur later in life.

**Methods:** This is a single case report. A 2.5-year-old boy presented to an emergency unit with 2–3 weeks of daily recurrent intestinal bleeding that was increasing and ongoing in the hours before admission. He had no weakness, abdominal pain, diarrhea, vomiting, or fever, and no recent medication or antibiotic use. Family history was unremarkable for intestinal disorders including inflammatory bowel disease. Physical examination showed a healthy-appearing child (weight 15 kg, height 94 cm) with profuse bright red rectal bleeding but no cardiovascular abnormalities, dysmorphic features, or psychomotor delay. Laboratory values showed microcytic anemia with hemoglobin of 7.8 g/dL, MCV 51.0 fL, and ferritin 6.0 µg/L, with no signs of inflammation or coagulation disturbances. Emergency upper and lower endoscopy was performed, followed by a control endoscopy 6 weeks later. Molecular genetic testing for EDS was subsequently conducted.

**Key Results:** Initial emergency endoscopy revealed a normal upper gastrointestinal tract but multiple lesions throughout the entire colon that suggested angiodysplasia. Two active bleeding sites in the cecum were successfully clipped. No further rectal bleeding occurred after the procedure. At follow-up endoscopy 6 weeks later, the previously described angiodysplasia-like lesions were no longer detectable, and the clips remained in place. However, desquamation of mucosal surfaces with consecutive superficial bleeding occurred simply by touching with the endoscope. Upon retraction of the endoscope, multiple lesions of mucosal desquamation with superficial bleeding were noted, even though the procedure was assessed as easy and uncomplicated. Extensive re-examination by an experienced neuropediatrician and syndromologist revealed no clinical abnormalities suggestive of a connective tissue disorder apart from hypermobility of the toes (but not other joints). Molecular genetic testing revealed a pathogenic loss-of-function mutation of the COL3A1 gene (c.1662+1G<A; p.?) associated with EDS type IV. Further investigations of large vessels, heart, and eyes showed no abnormalities typical for EDS type IV.

**Clinical Implications:** This case demonstrates that EDS type IV can present with isolated lower gastrointestinal bleeding in very young children, even in the complete absence of typical clinical features such as dysmorphias, joint hypermobility (beyond isolated toe hypermobility), or vascular abnormalities. The finding of mucosal fragility with contact bleeding during endoscopy should raise suspicion for a connective tissue disorder. Early detection is crucial to allow regular screening for and prevention of significant complications like rupture of large arterial vessels. This is one of the earliest presentations of mucosal intestinal abnormalities in a patient with confirmed EDS type IV, and the authors note it is the earliest presentation of EDS type IV with intestinal complications reported to date.