Megacystis–microcolon–intestinal hypoperistalsis syndrome (MMIHS) due to a de novo ACTG2 mutation: A neonatal case report

Abstract

Background

Megacystis–microcolon–intestinal hypoperistalsis syndrome (MMIHS) is a rare congenital visceral myopathy characterized by severe gastrointestinal dysmotility and bladder dysfunction, most commonly associated with ACTG2-mutations.

Case report

We report a preterm neonate with prenatally detected megacystis and a de novo heterozygous ACTG2 variant (c.593G>T; p.Gly198Val). Postnatally, the patient developed progressive abdominal distension and feeding intolerance. Imaging demonstrated dilated bowel loops and microcolon. Exploratory laparotomy on day 5 confirmed dilated ileum, microcolon, and massive megacystis without mechanical obstruction. Gastrostomy and ileostomy were performed. The patient required parenteral nutrition followed by gradual enteral feeding with stool recirculation. Clean intermittent catheterization and antibiotic prophylaxis were initiated.

Conclusion

MMIHS should be suspected in cases of fetal megacystis. Early genetic diagnosis and multidisciplinary management, including intestinal failure rehabilitation and urological care, are essential to improve outcomes.

Introduction

Megacystis–microcolon–intestinal hypoperistalsis syndrome (MMIHS) is a rare congenital disorder characterized by severe impairment of smooth muscle function involving both the gastrointestinal and urinary systems. It is defined by the triad of megacystis without mechanical obstruction, microcolon, and intestinal hypoperistalsis [1].

Pathogenic variants in the ACTG2 gene, encoding γ-2 smooth muscle actin, represent the most common genetic cause. These mutations impair smooth muscle contractility, leading to intestinal dysmotility and bladder dysfunction [2], [3].

Prenatal detection of fetal megacystis may raise suspicion of MMIHS. After birth, affected neonates typically present with abdominal distension, feeding intolerance, and failure to establish effective intestinal transit, frequently evolving into intestinal failure [4].

We report a neonate with genetically confirmed MMIHS due to a de novo ACTG2 mutation, focusing on early surgical and intestinal failure management.

Case report

During the second trimester, prenatal ultrasound revealed marked fetal bladder distension. Villocentesis identified a de novo heterozygous ACTG2 variant (c.593G>T; p.Gly198Val), with normal karyotype and array comparative genomic hybridization.

The infant was delivered at 36 + 5 weeks’ gestation with a birth weight of 2.8 kg and Apgar scores of 10/10. Meconium passage occurred shortly after birth.

A CH 6 Foley urinary catheter, nasogastric tube, and central venous catheter were placed. Initial abdominal radiography showed gastric distension and dilated bowel loops, with air present all the way to the rectum (Fig. 1). The patient was kept nil per os and started on parenteral nutrition and antibiotic prophylaxis.

Fig. 1.

X-ray on the first day of life.

On day 4, a contrast gastrointestinal study showed reduced gastric motility and dilated hypotonic intestinal loops. The colon appeared opacified after 17 h but markedly reduced in caliber.

On day 5, exploratory laparotomy revealed dilated ileum, microcolon, and massive megacystis without mechanical obstruction. Gastrostomy and ileostomy were performed. No bowel resection was required.

Postoperatively, clean intermittent bladder catheterization was initiated together with antibiotic prophylaxis with cefixime. One episode of urinary tract infection caused by Enterobacter cloacae occurred and resolved following treatment with ampicillin/sulbactam and ceftazidime.

Serial ultrasound examinations did not demonstrate dilation of the urinary tract.

The patient required parenteral nutrition, initially continuous and subsequently cycled. Enteral feeding with breast milk and formula was gradually introduced from postoperative day 10 and progressively increased. Fecal output was regular and spontaneously through the stoma. Stool recirculation between stomas was initiated two weeks after surgery. The patient’s growth was adequate.

One month after surgery, a contrast radiography from distal stoma was performed to complete the evaluation of the gastrointestinal tract. The ileal loops appeared normal in caliber, whereas the large bowel loops showed reduced caliber consistent with the underlying disease. The contrast reached the rectum and anal canal with normal evacuation (Fig. 2).

Fig. 2.

Contrast radiography from distal stoma.

Discussion

Megacystis–microcolon–intestinal hypoperistalsis syndrome (MMIHS) is a rare and severe congenital disorder first described by Berdon et al. in 1976 and currently classified within the spectrum of visceral myopathies [1]. It is characterized by profound impairment of smooth muscle contractility involving both the gastrointestinal and urinary tracts, leading to functional intestinal obstruction and bladder dysfunction in the absence of a mechanical cause.

In recent years, heterozygous variants in the ACTG2 gene have been identified as the most common genetic cause of MMIHS [2], [3]. The ACTG2 gene encodes γ-2 smooth muscle actin, a key component of the contractile apparatus of visceral smooth muscle cells. Pathogenic variants, most frequently missense mutations, disrupt actin filament assembly and impair contractile function. These alterations result in ineffective peristalsis and impaired bladder emptying.

Notably, many variants occur de novo, highlighting the importance of genetic testing even in the absence of a positive family history. Recent studies have also suggested genotype–phenotype correlations, with specific variants associated with more severe clinical presentations and earlier onset of intestinal failure [5], [6].

Prenatal diagnosis of MMIHS has become increasingly feasible due to advances in fetal imaging. Fetal megacystis, particularly when persistent and associated with normal amniotic fluid and absence of structural obstruction, should raise suspicion for an underlying visceral myopathy. However, the differential diagnosis remains broad and includes posterior urethral valves, urethral atresia, and other causes of lower urinary tract obstruction. The integration of next-generation sequencing into prenatal work-up has improved diagnostic accuracy [7].

Postnatally, patients typically present with abdominal distension, feeding intolerance, and failure to establish effective intestinal transit [8]. In our case, early meconium passage did not exclude the diagnosis, underscoring that intestinal hypoperistalsis may be partial or progressive in the early neonatal period. Imaging studies demonstrating dilated bowel loops and microcolon support the diagnosis but are not pathognomonic. Surgical exploration remains important to exclude mechanical obstruction and to guide management.

The management of MMIHS is complex and requires a multidisciplinary approach. Most patients develop intestinal failure due to severe dysmotility and inability to tolerate full enteral feeding. In this setting, early initiation of parenteral nutrition is essential to ensure adequate growth and metabolic stability. However, long-term parenteral nutrition is associated with significant complications, including catheter-related infections, intestinal failure–associated liver disease (IFALD), and metabolic disturbances. Recent advances in lipid emulsions and catheter care protocols have contributed to reducing these complications and improving long-term outcomes [9].

Surgical interventions, such as gastrostomy and ileostomy, play a crucial role in decompressing the gastrointestinal tract, reducing abdominal distension, and facilitating nutritional management. In our patient, early surgical decompression allowed for improved tolerance of enteral feeding and implementation of intestinal rehabilitation strategies.

Intestinal rehabilitation represents a key component of management and aims to promote intestinal adaptation and reduce dependence on parenteral nutrition. In our case, early gradual introduction of enteral feeding combined with stool recirculation between stomas was associated with good growth and clinical stability. Stool recirculation may enhance nutrient absorption, preserve microbiota diversity, and stimulate mucosal adaptation, although current evidence remains limited and largely derived from small series [10].

Urological management is equally important, as bladder dysfunction may lead to urinary retention, recurrent infections, and progressive renal damage. Clean intermittent catheterization is considered the standard of care and was successfully implemented in our patient. The occurrence of a urinary tract infection highlights the need for close monitoring and appropriate prophylactic strategies [7].

The prognosis of MMIHS has historically been poor, with high mortality in early infancy. However, advances in neonatal intensive care, parenteral nutrition, and multidisciplinary intestinal failure programs have improved survival rates. Selected patients may achieve partial enteral autonomy, although many remain dependent on long-term nutritional support [9].

This case highlights several important clinical aspects. First, prenatal detection of megacystis combined with genetic testing enables early diagnosis and appropriate perinatal planning. Second, early surgical intervention and structured intestinal rehabilitation may improve clinical outcomes. Third, coordinated multidisciplinary care involving neonatologists, pediatric surgeons, gastroenterologists, and urologists is essential for optimal management.

Further research is needed to better define genotype–phenotype correlations of ACTG2 variants and to develop targeted therapeutic strategies aimed at improving smooth muscle function. In addition, long-term follow-up studies are required to evaluate outcomes, complications, and quality of life in survivors.

Conclusion

MMIHS is a rare but severe congenital disorder frequently resulting in neonatal intestinal failure. Early diagnosis through prenatal imaging and genetic testing enables prompt multidisciplinary management.

This case underscores the importance of early surgical decompression, structured intestinal rehabilitation, and proactive urological care in improving clinical outcomes in patients with ACTG2-related visceral myopathy.

CRediT authorship contribution statement

Marco Di Mitri: Supervision. Antonino Morabito: Supervision. Riccardo Coletta: Supervision. Michele Maria Cantagalli: Writing – review & editing, Conceptualization. Tommaso Amato: Writing – review & editing, Writing – original draft, Investigation, Conceptualization.

Patient's/Guardian's consent

Informed consent for publication of these case reports was obtained from the patients.

Ethical clearance

The publication of this case report was approved by the ethics committee (approval number: PA_12/2026), and consent to publish was obtained from the patient’s parents.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.