Study: GI complications common in classical-like EDS type 1
Spontaneous intestinal perforation, diverticulosis appear often in cases
People with classical-like Ehlers-Danlos syndrome type 1 (clEDS1) have an increased risk of gastrointestinal tract (GI) complications, according to a new case series.
Ten of the 15 investigated patients had at least one spontaneous intestinal perforation and nearly all had diverticulosis, or small pouches that push outward through weak spots in the colon wall.
“The study emphasizes the need for specialized care and suggests that all individuals with clEDS1 should be managed cautiously during GI interventions and intubation to prevent life-threatening complications,” the researchers wrote. The study, “Tenascin-X Deficiency Causing Classical-Like Ehlers-Danlos Syndrome Type 1 in Humans is a Significant Risk Factor of Gastrointestinal and Tracheal Ruptures,” was published in Clinical and Translational Gastroenterology.
Classical EDS and classical-like EDS are types of EDS, a group of hereditary connective tissue disorders characterized by soft, stretchy skin and unusually mobile joints. These types have similar clinical manifestations, but the underlying genetic causes are different.
Classical-like EDS type 1, or clEDS1, is caused by mutations in the TNXB gene, which lead to a deficiency in tenascin-X (TNX), a protein that helps maintain connective tissues. It’s extremely rare, with 56 cases reported in the literature as of 2022. A second subtype of classical-like EDS, called clEDS type 2, is caused by AEBP1 mutations.
Studies suggest that individuals with clEDS1 may also have complications related to the GI tract, such as ulcers, spontaneous perforation of the intestines, and diverticulosis. Ruptures of the windpipe, or trachea, have also been reported.
Severe GI symptoms have been linked to other types of EDS, but they haven’t been fully described in the classical-like form of the condition.
“Thus, an adequate overview of the nature and severity of GI symptoms in clEDS1 is essential,” wrote an international team of researchers, who retrospectively reviewed 15 unrelated people with clEDS1 and GI and/or tracheal complications.
GI concerns in classical-like EDS type 1
Eleven of the patients were women and about half (53%) developed clEDS1 symptoms in childhood. Still, the median age at diagnosis was 46, ranging from 22 to 69. Multiple joint dislocations and increased bleeding were the most common symptoms that led to a diagnosis in the people studied.
Among common EDS symptoms, 13 (87%) had stretchy skin, and eight (53%) had unusually mobile joints. Of the eight with fragile skin, six (40%) had signs of delayed wound healing.
Two-thirds of the patients (67%) had spontaneous intestinal perforations, all occurring after age 20 and half before age 40. In about half the patients (46%), a clEDS1 diagnosis was known before the first perforation, arising a median of 11 years after diagnosis.
Spontaneous perforations were seen throughout the GI tract. Five patients had one in the small intestine, three in the colon, two in the middle section of the small intestine, called the jejunum, and one in the duodenum, or the first section of the small intestine. Seven patients had non-spontaneous perforations after a GI-related medical intervention and six were due to a predisposing condition. Six patients (46%) had multiple GI perforations. In the general population, spontaneous and non-spontaneous perforations of the bowel are rare, the researchers noted.
Other than the TNX deficiency, no notable risk factors related to a GI perforation were found. Moreover, the severity of other clEDS1 symptoms wasn’t predictive of GI fragility.
Almost all (80%) had diverticulosis, while six (40%) had severe or complete constipation. Ten patients had other GI diseases, such as irritable bowel syndrome, GI bleeding, ileus (a lack of muscle contractions that move food through the intestines), and ileitis (inflammation of the ileum, a portion of the small intestine). Six patients reported unexplained abdominal pain.
Tracheal rupture was seen in three people, all of whom had GI complications, and all were caused by a medical intervention. While six patients had heart disease, no apparent abnormalities in their blood vessels were noted.
“Our findings offer valuable insights for the clinical management of clEDS1 and underscore the importance of specialized care, providing a foundation for improved clinical guidelines and preventive strategies,” the researchers wrote.
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