Digestion and intestinal absorption allow the body to sustain itself and are the emblematic functions of the bowel. On the flip side, functions also arise from its role as an interface with the environment. Indeed, the gut houses microorganisms, collectively known as the gut microbiota, which interact with the host, and is the site of complex immune activities. Its role in human pathology is complex and scientific evidence is progressively elucidating the functions of the gut, especially regarding the pathogenesis of chronic intestinal diseases and inflammatory conditions affecting various organs and systems. This editorial aims to highlight and relate the factors involved in the pathogenesis of intestinal and systemic inflammation.

It is challenging to manage schizophrenic catatonia and comorbid chronic intestinal pseudo-obstruction (CIPO). The pathology of catatonia is unclear. There are few reports or research on this issue. In this case, we present a middle-aged woman diagnosed with schizophrenia with catatonic features and comorbid CIPO. In the treatment process, modified electroconvulsive therapy (mECT) improved her stupor and CIPO partially. Lorazepam alleviated her stupor and CIPO completely. It is the first report describing complete remission with lorazepam in patient suffering from comorbid schizophrenic catatonia and CIPO, which may benefit the exploration of pathophysiology and treatment of comorbidity of schizophrenia with catatonia and CIPO.

Chronic intestinal pseudo-obstruction (CIPO) is a rare syndrome characterized by signs of intestinal obstruction lasting for 6 months or more, in the absence of a definitive cause of obstruction. We report a case of CIPO in a 49-year-old female patient with a 6-month history of ongoing irregular bowel movements, manifested as constipation and diarrhea accompanied by abdominal pain and bloated feeling. Contrast-enhanced abdominal computed tomography and magnetic resonance enterography revealed focal thickening of a segment of the lienal flexure and intermittent areas of wider and narrower caliber along the sigmoid colon. No signs of a definitive cause of obstruction were found, but evidence for dolichosigma was revealed, which was later confirmed with colonoscopy. Due to persisting symptoms, the patient agreed to elective resection of the sigmoid colon. Following the procedure, symptoms regressed with a significant improvement in the quality of life. The patient has been regularly monitored in an outpatient setting and reports absence of the symptoms since the procedure. Pathophysiology of the resected section revealed more prominent lymphatic tissue, follicular arrangement, and reactively altered germinal centers, which can suggest CIPO.

Pediatric intestinal pseudo-obstruction (PIPO) is a heterogeneous condition characterized by impaired gastrointestinal propulsion, a broad clinical spectrum, and variable severity. Several molecular bases underlying primary PIPO have been identified, of which autosomal dominant ACTG2-related visceral myopathy is the most common in both familial or sporadic primary PIPO cases. We present a family with autosomal recessive ACTG2-related disease in which both parents have mild gastrointestinal symptoms and sons have severe PIPO and bladder dysfunction.
UNASSIGNED: Clinical genome sequencing was performed on the patients and the mother. Immunohistochemistry was performed on intestinal tissue from the patients to show expression levels of the ACTG2.
UNASSIGNED: Genome sequencing identified a 6.8 kb 2p13.1 loss that includes the ACTG2 gene and a maternally inherited missense variant p.Val10Met in the ACTG2 gene.
UNASSIGNED: This case demonstrates that monoallelic hypomorphic ACTG2 variants may underly mild primary gastrointestinal symptoms, while biallelic mild variants can cause severe diseases. The Deletions of the noncoding ACTG2 exon can be an under-recognized cause of mild gastrointestinal symptoms unidentifiable by exome sequencing, explaining some instances of interfamilial variability with an apparent autosomal dominant inheritance. Genome sequencing is recommended as a genetic work-up for primary or idiopathic PIPO because of genetic heterogeneity.

Severe gut motility disorders are characterized by ineffective propulsion of intestinal contents. As a result, patients often develop extremely uncomfortable symptoms, ranging from nausea and vomiting along with alterations of bowel habits, up to radiologically confirmed subobstructive episodes. Chronic intestinal pseudo-obstruction (CIPO) is a typical clinical phenotype of severe gut dysmotility due to morphological and functional alterations of the intrinsic (enteric) innervation and extrinsic nerve supply (hence neuropathy), interstitial cells of Cajal (ICCs) (mesenchymopathy), and smooth muscle cells (myopathy). In this chapter, we highlight some molecular mechanisms of CIPO and review the clinical phenotypes and the genetics of the different types of CIPO. Specifically, we will detail the role of some of the most representative genetic mutations involving RAD21, LIG3, and ACTG2 to provide a better understanding of CIPO and related underlying neuropathic or myopathic histopathological abnormalities. This knowledge may unveil targeted strategies to better manage patients with such severe disease.

Smooth muscle disorders affecting both the intestine and the bladder have been known for a decade. However, the recent discovery of genes associated with these dysfunctions has led to the description of several clinical phenotypes. We performed a systematic review of all published cases involving seven genes with pathogenic variants, ACTG2, MYH11, FLNA, MYLK, RAD21, MYL9 and LMOD1, and included 28 articles describing 112 patients and 5 pregnancies terminated before birth. The most commonly described mutations involved ACTG2 (75/112, 67% of patients), MYH11 (14%) and FLNA (13%). Twenty-seven patients (28%) died at a median age of 14.5 months. Among the 76 patients for whom this information was available, 10 (13%) had isolated chronic intestinal pseudo-obstruction (CIPO), 17 (22%) had isolated megacystis, and 48 (63%) had combined CIPO and megacystis. The respective proportions of these phenotypes were 9%, 20% and 71% among the 56 patients with ACTG2 mutations, 20%, 20% and 60% among the 10 patients with MYH11 mutations and 50%, 50% and 0% among the 7 patients with FLNA mutations.

Background: Pediatric Intestinal Pseudo-obstruction (PIPO) is a congenital enteric disorder characterized by severe gastrointestinal (GI) dysmotility, without mechanical obstruction. Although several genes have been described to cause this disease, most patients do not receive a genetic diagnosis. Here, we aim to identify the genetic cause of PIPO in a patient diagnosed with severe intestinal dysmotility shortly after birth. Methods: Whole exome sequencing (WES) was performed in the patient and unaffected parents, in a diagnostic setting. After identification of the potential disease-causing variant, its functional consequences were determined in vitro and in vivo. For this, expression constructs with and without the causing variant, were overexpressed in HEK293 cells. To investigate the role of the candidate gene in GI development and function, a zebrafish model was generated where its expression was disrupted using CRISPR/Cas9 editing. Results: WES analysis identified a de novo heterozygous deletion in TFAP2B (NM_003221.4:c.602-5_606delTCTAGTTCCA), classified as a variant of unknown significance. In vitro studies showed that this deletion affects RNA splicing and results in loss of exon 4, leading to the appearance of a premature stop codon and absence of TFAP2B protein. Disruption of tfap2b in zebrafish led to decreased enteric neuronal numbers and delayed transit time. However, no defects in neuronal differentiation were detected. tfap2b crispants also showed decreased levels of ednrbb mRNA, a downstream target of tfap2b. Conclusion: We showed that TFAP2B haploinsufficiency leads to reduced neuronal numbers and GI dysmotility, suggesting for the first time, that this gene is involved in PIPO pathogenesis.

Vitamin A has an essential role in the maintenance of corneal and conjunctival epithelization, as well as photoreceptor transduction in the retina. A deficiency of vitamin A causes keratinization of the surface epithelium, and night blindness is often the first symptom. This report describes a case of chronic intestinal pseudo-obstruction (CIPO), a rare and potentially fatal disease, diagnosed following detection of a vitamin A deficiency in an ophthalmological examination. A 25-year-old female patient presented with a 3-month history of dryness, a burning sensation, and decreased vision, especially at night, in both eyes. She appeared cachectic and ill, and reported having lost 10 kg in the previous year. An ophthalmological examination revealed conjunctival and corneal keratinization in addition to punctate keratopathy with xerosis in both eyes, which raised the suspicion of a vitamin A deficiency. Her serum vitamin A level confirmed the diagnosis, and she was referred to the gastroenterology clinic, where she was diagnosed with CIPO and treated with parenteral multivitamin supplementation. A vitamin A deficiency should be suspected in patients with malnourishment and xerosis. Rapid diagnosis and treatment can be life-saving in cases with a severe underlying pathology.

Hollow visceral myopathy (HVM) is described as impaired intestinal function and motility in the absence of mechanical obstruction. In this case report, we describe a unique case of an 18-year-old female who presented to the hospital with complaints of persistent nausea, vomiting, inability to tolerate oral feeds, and substantial weight loss for 2 months. After appropriate investigations, a diagnosis of gastroparesis was established. The patient was started on metoclopramide, which led to significant symptomatic improvement, and she was eventually discharged home. One month after discharge, she presented to the hospital with symptoms similar to her initial presentation. After further laboratory and radiological investigation, she was diagnosed with severe gastroparesis and chronic intestinal pseudo-obstruction. Over the next month, the patient was given an extensive trial of multiple prokinetic agents such as mirtazapine, ondansetron, pyridostigmine, octreotide, and promethazine, but she failed to show clinical improvement. Due to failure of medical therapy, a nasojejunal feeding tube was placed for enteral nutrition. However, the patient reported worsening of her symptoms despite slow feeding rates; hence, a decision was made to start the patient on total parenteral nutrition and transfer her to a larger tertiary center for higher level of care. At the tertiary hospital, the patient was continued on total parenteral nutrition and underwent extensive evaluation. Ultimately, she was diagnosed with HVM after a laparoscopic full-thickness intestinal biopsy showed histopathological evidence of the disease. She underwent isolated small intestine transplant, which led to significant improvement of her symptoms and was eventually discharged home. The patient continues to be symptom-free and follows up with Gastroenterology and Transplant Surgery regularly. This case report highlights a rare clinical condition, HVM, as a potential diagnosis in patients with clinical features of intestinal obstruction without mechanical obstruction.

Chronic intestinal pseudo-obstruction (CIPO) is an extremely rare condition with symptoms of recurrent intestinal obstruction without any lesions. The outcomes of pediatric CIPO and predictors for the outcomes have not yet been well established. We analyzed the clinical outcomes and associated factors for the outcomes of pediatric CIPO. We retrospectively reviewed 66 primary CIPO patients diagnosed between January 1985 and December 2017. We evaluated parenteral nutrition (PN) factors such as PN duration, PN use over 6 months, home PN, and mortality as outcomes. We selected onset age, presence of urologic symptoms, pathologic type, and involvement extent as predictors. The early-onset CIPO was found in 63.6%, and 21.2% of the patients presenting with urologic symptoms. Of the 66 patients, 47 and 11 had neuropathy and myopathy, respectively. The generalized involvement type accounted for 83.3% of the cases. At the last follow-up, 24.2% of the patients required home PN management. The mean duration of PN was 11.8 ± 21.0 months. The overall mortality rate of primary CIPO was 18.2%. PN factors were predicted by the urologic symptoms and extent of involvement. However, mortality was predicted by pathologic type. The onset age was not significantly associated with the outcomes. CIPO with urologic symptoms and generalized CIPO had poor PN outcomes. Myopathy is suggested as a predictor of mortality in children with primary CIPO.