Undifferentiated Connective Tissue Dysplasia and Collagen Remodeling as a Pathogenetic Basis of Dolichosigmoid in Children With Chronic Constipation

Chronic constipation in children is a multifactorial condition in which impaired intestinal motility, structural characteristics of the colon, and systemic connective tissue abnormalities may coexist. The established association between constipation and increased connective tissue laxity, together with the high prevalence of dolichocolon among children with gastrointestinal complaints, raises the question of shared mechanisms underlying these conditions. However, the pathophysiological significance of dolichosigmoid and the role of altered collagen homeostasis in undifferentiated connective tissue dysplasia remain insufficiently understood. In this context, investigating the relationship between the severity of connective tissue dysplasia, markers of collagen remodeling, and the clinical course of chronic constipation may help clarify the mechanisms underlying dolichosigmoid development and identify a clinical and biochemical phenotype of children with a more severe disease course. Objective. To characterize connective tissue metabolism in children with chronic constipation associated with congenital elongation of the sigmoid colon and to assess the relationship between biochemical markers of collagen degradation, the severity of undifferentiated connective tissue dysplasia, and the clinical course of the disease. Materials and Methods.A comparative analysis was performed of serum free hydroxyproline and antibodies to type I–V collagens in children with chronic constipation associated with dolichosigmoid, stratified according to the severity of dysplastic manifestations and the clinical stage of the disease. The diagnostic characteristics of the investigated biomarkers were also assessed.All studies were conducted in accordance with the fundamental provisions of the Laws of Ukraine No. 2801-XII and No. 3447-IV, ICH GCP (1996–2016), the Declaration of Helsinki of the World Medical Association on Ethical Principles for Medical Research Involving Human Subjects (1964–2013), the Council of Europe Convention on Human Rights and Biomedicine (04.04.1997), Directive 2010/63/EU of the European Union, Orders of the Ministry of Health of Ukraine No. 690 dated September 23, 2009, No. 944 dated December 14, 2009, and Order of the Ministry of Education and Science of Ukraine No. 249 dated March 1, 2012. This article is a fragment of the research project of the Department of Pediatrics and Medical Genetics of Bukovinian State Medical University entitled “Improvement of Diagnosis, Treatment, and Prognosis of Gastrointestinal Diseases in Children,” state registration No. 0123U102018, conducted from January 1, 2023, to December 31, 2027. Results.Children with chronic constipation demonstrated substantial alterations in biochemical indicators of connective tissue metabolism. The serum concentration of free hydroxyproline was 4.03±0.06 μg/mL compared with 1.41±0.34 μg/mL in the control group (p<0.001), indicating increased collagen degradation. The elevation of this marker was more pronounced in patients with more severe manifestations of undifferentiated connective tissue dysplasia and a less favorable clinical course. The concentration of antibodies to type I–V collagens was also higher than in controls (8.11±0.01 vs. 2.40±0.01 U/mL; p<0.001), with the highest levels observed in patients with the most pronounced dysplastic changes. A positive correlation was identified between the severity of connective tissue dysplasia and the levels of the investigated biomarkers. Conclusions.The findings indicate the presence of pronounced metabolic alterations of connective tissue in children with chronic constipation and dolichosigmoid, the magnitude of which is associated with the severity of the dysplastic phenotype and the clinical severity of the disease. The combined assessment of phenotypic and biochemical features may represent a promising approach for objectively characterizing the severity of connective tissue abnormalities and improving individualized management of children with this form of chronic constipation.