Berdon syndrome

 Berdon syndrome

Overview

Berdon syndrome, also known as megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), is a rare, generally fatal autosomal recessive genetic disorder characterized by an abnormally large, non-obstructed urinary bladder (megacystis), an underdeveloped colon (microcolon), and reduced or absent intestinal peristalsis (hypoperistalsis), leading to functional intestinal obstruction. Symptoms include severe abdominal distension, failure to pass meconium, and voiding problems. While historically having a poor prognosis, advances in supportive treatments and management have led to increased survival rates.  

Symptoms

Megacystis: A significantly enlarged and non-obstructed urinary bladder, often visible on prenatal ultrasound, which is the most prominent symptom. 

Microcolon: An abnormally small colon. 

Intestinal Hypoperistalsis: Poor or absent movement of the intestinal muscles, leading to a lack of normal peristalsis. 

Abdominal Distention: Swelling or bulging of the abdomen, often from the distended bladder and dilated stomach and bowels. 

Causes 

Genetic Mutations:

ACTG2 Gene Mutations: The most common cause, leading to altered gamma-2 actin protein that impairs muscle contraction in the urinary and intestinal tracts. 

Other Gene Mutations: Mutations in genes like MYH11, MYLK, LMOD1, and MYL9 can also cause MMIHS by affecting smooth muscle contraction. 

Unknown Causes: In about 50% of cases, the genetic cause cannot be identified, suggesting other unknown genes may be involved. 

Pathogenesis

Impaired Muscle Function: The core problem is the inability of smooth muscles in the bladder and intestines to contract effectively. 

Obstruction of Function: This lack of muscle contraction leads to a buildup of urine in the bladder (megacystis) and poor movement of food and waste through the intestines (intestinal hypoperistalsis). 

Secondary Symptoms: The dysfunctional intestinal peristalsis can also lead to a microcolon (abnormally small colon) and symptoms similar to intestinal obstruction. 

Genetic Inheritance:

Autosomal Recessive: Berdon syndrome typically follows an autosomal recessive pattern of inheritance, meaning an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition. 

Familial Link: This is supported by its frequent occurrence in families with consanguineous parents and affected siblings. 

Diagnosis

Prenatal Diagnosis 

Fetal Ultrasound and MRI: A diagnosis can be made during pregnancy, typically in the second trimester, by identifying an enlarged fetal bladder (megacystis), which is a hallmark sign. Bilateral hydroureteronephrosis (swelling of the kidneys and ureters) and dilated stomach or bowel loops may also be seen.

Amniotic Fluid Analysis: Analysis of amniotic fluid can sometimes show elevated γ-glutamyl transpeptidase and aminopeptidase M, which can support the prenatal diagnosis.

Postnatal Diagnosis

Clinical Presentation: After birth, newborns may show signs of an intestinal obstruction, such as abdominal distension and bilious (yellow-green) vomiting, and may fail to pass meconium. 

Imaging Studies:

Abdominal X-ray: May show a distended stomach and dilated small bowel with a lack of gas in the lower colon. 

Upper Gastrointestinal Series: Fluoroscopic studies reveal a dilated stomach and small intestine, potentially with associated malrotation. 

Contrast Enema: Demonstrates a small-caliber colon (microcolon) and can also show malrotation. 

Urologic Imaging: A dilated bladder, hydroureteronephrosis, and vesicoureteral reflux (VUR) are seen on kidney/bladder ultrasounds and cystography. 

Urodynamic Studies: May show a non-contractile bladder. 

Other Diagnostic Clues

Genetic Testing: While not always necessary for initial diagnosis, genetic testing can identify underlying genetic causes. 

Surgical Findings: During surgery, the presence of a greatly enlarged bladder, microcolon, dilated small bowel loops, and a lack of intestinal muscle contractions are confirming features. 

Treatment

Nutritional Support 

Total Parenteral Nutrition (TPN): The primary treatment for the gastrointestinal dysfunction is to provide nutrients intravenously, as the intestines are unable to absorb them effectively.

Enterostomies: Surgical procedures such as gastrostomies, jejunostomies, or ileostomies may be used to administer nutrition and decompress the bowel.

Urinary Management

Urinary Catheterization: Intermittent or long-term catheterization helps drain urine from the distended bladder. 

Vesicostomy: A surgical opening of the bladder to the skin to provide a route for continuous urine drainage is a common intervention to relieve bladder distension and prevent complications. 

Surgical Interventions

Ileostomy/Jejunostomy: These procedures create an opening in the small intestine to allow for drainage and decompression of the distended bowel, which can improve the management of intestinal failure and allow for earlier oral feeding. 

Multivisceral Transplantation: This is the only accepted treatment that offers potential long-term survival for some patients with Berdon syndrome. It involves transplanting multiple organs, such as the stomach, pancreas, liver, small intestine, and large intestine, to replace the non-functioning organs. 

Type of Doctor Department : A pediatric gastroenterologist, pediatric surgeon, and potentially a pediatric nephrologist or urologist.