SNP Shot: Genomic Insights

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a serious condition affecting the muscles of the bladder and intestines. It disrupts the normal muscle contractions (peristalsis) that move food through the digestive system and empty the bladder.

MMIHS can sometimes be detected before birth via ultrasound. Affected fetuses often exhibit an enlarged bladder (megacystis) due to its inability to empty. Additionally, the large intestine (colon) may be abnormally narrow (microcolon) because of insufficient functional muscle lining. These intestinal and bladder issues persist throughout the individual's life.

Following birth, impaired peristalsis (hypoperistalsis) often leads to intestinal pseudo-obstruction, a condition that mimics a physical blockage in the intestines without an actual obstruction. This causes a buildup of partially digested food, resulting in abdominal swelling (distention), pain, nausea, and vomiting. The vomit often contains bile, a green or yellow digestive fluid. Because digestion is impaired and the body doesn't receive adequate nutrients, nutritional support is typically required through intravenous feedings (parenteral nutrition). Some individuals may depend solely on intravenous feedings, while others need it only occasionally. However, long-term parenteral nutrition can lead to liver complications.

The reduced ability to urinate also contributes to painful abdominal distention. Many individuals with MMIHS require a urinary catheter to drain urine from their bladder.

Intestinal malrotation, a condition where the intestines do not fold correctly and may twist abnormally, causing a blockage, is another possible abnormality in some MMIHS patients. Additionally, individuals with MMIHS may develop problems with their kidneys or ureters, the tubes that carry urine from the kidneys to the bladder.

The life expectancy of those with MMIHS is generally shorter than average, often due to malnutrition, severe infection (sepsis), or multiple organ failure.

Inheritance:

When MMIHS is caused by mutations in the ACTG2 gene, it is inherited in an autosomal dominant manner. This means that only one copy of the mutated gene in each cell is enough to cause the condition. These cases often arise from new (de novo) mutations that occur during the formation of egg or sperm cells or during early embryonic development. In such instances, there is no family history of the disorder. When MMIHS is caused by mutations in other identified genes, it is inherited in an autosomal recessive manner. This means that both copies of the gene in each cell must carry a mutation for the condition to develop. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but usually do not show any symptoms of the condition.