Pyloric stenosis and genetics
Pyloric stenosis, also known as infantile hypertrophic pyloric stenosis, is a condition where the pylorus, the muscle at the entrance of the small intestine from the stomach, becomes enlarged, preventing food from passing through. This occurs primarily in infants, typically between three to twelve weeks old, and affects about three in every thousand births. The condition is more common in males, especially firstborns, and is associated with certain risk factors, including a family history of pyloric stenosis and prematurity.
Genetically, pyloric stenosis appears to be multifactorial, meaning that various genetic and environmental influences contribute to its occurrence. Researchers have identified several genes, specifically five associated with increased susceptibility, though the inheritance pattern is not straightforward. While there are rare cases of autosomal dominant inheritance, most instances do not follow a predictable genetic pattern. Symptoms usually include forceful vomiting, persistent hunger, dehydration, and weight loss. Diagnosis is typically made through physical examination and imaging tests, with treatment primarily involving a surgical procedure called pyloromyotomy to alleviate the blockage. There are no known preventative measures, although breastfeeding may potentially lower the risk.
Pyloric stenosis and genetics
ALSO KNOWN AS: Infantile hypertrophic pyloric stenosis
DEFINITION Food passes from the stomach to the small intestine. In pyloric stenosis, food cannot pass freely because the entrance between the stomach and the small intestine narrows. The narrowing is caused by the enlargement of the pylorus (the muscle at the entrance of the opening from the stomach to the small intestine). Almost all cases of pyloric stenosis happen in very young babies (usually three to twelve weeks old). This problem occurs about three times out of every one thousand births. It is four times more common in males than in females. The sooner pyloric stenosis is treated, the fewer problems will result and the healthier a baby will be, so parents who think their child has this condition should contact their doctors immediately.
Risk Factors
The following risk factors increase a baby’s chance of developing pyloric stenosis; parents whose child has any of these risk factors should tell their doctor. Risk factors include prematurity and a family history of pyloric stenosis. Pyloric stenosis is more common in male babies (particularly firstborn males) and more common in Caucasian than in Latino, Asian, or African American babies.
Etiology and Genetics
The of pyloric stenosis is multifactorial, suggesting that there is a broad range of genetic and environmental factors that may contribute to the appearance of this birth defect. While there is no single gene that when mutated will always cause this condition, researchers have identified at least five genes in which mutations may significantly increase the risk of developing this disorder. Since input from several genes is probably involved, most cases do not conform to a predictable pattern of inheritance. Scattered reports in the literature note isolated families in which pyloric stenosis is inherited as an autosomal dominant condition, but these are exceptions to the norm. In autosomal dominant inheritance, a single copy of the mutation is sufficient to cause full expression of the trait. An affected individual has a 50 percent chance of transmitting the mutation to each of his or her children.
The five genes that are known to be associated with increased susceptibility to the development of pyloric stenosis are known as IHPS1-5, with the gene letters standing for infantile hypertrophic pyloric stenosis. IHPS1 is located on the long arm of chromosome 12, at position 12q24.2–q24.31, and IHPS2 is located on chromosome 16 at position 16p13–p12. The remaining genes are IHPS3 (at position 11q14–q22), IHPS4 (at position Xq23), and IHPS5 (at position 16q24.3). Little is known about the cellular action or interaction of the protein products of these genes or the molecular mechanism by which susceptibility may be increased.
Other risk factors include diseases such as diabetes, excessive acid in the duodenum, and some antibiotics.
Symptoms
Symptoms of pyloric stenosis usually begin when babies are three to five weeks old. They include forceful vomiting of formula or milk; acting hungry most of the time; weight loss; signs of dehydration, such as less urination, dry mouth, and crying without tears; tiredness; fewer bowel movements; and blood-tinged vomit (which happens when repeated vomiting irritates the stomach, causing mild stomach bleeding).
Screening and Diagnosis
The doctor will ask about the symptoms a child is experiencing and about his or her medical history. The doctor will also perform a physical examination. An olive-shaped knot caused by the presence of pyloric stenosis is often felt by the experienced examiner. If a baby is diagnosed with pyloric stenosis, parents and their families will be referred to a pediatric surgeon (a doctor specializing in surgery in children).
Tests may include an abdominal ultrasound, a procedure that uses sound waves to make detailed computer pictures of the inside of the abdomen. Tests may also include a barium upper gastrointestinal x-ray series. A medicine (barium) is swallowed to outline the esophagus and stomach. X-ray pictures of the abdomen can then tell if food is moving normally through the stomach.
Treatment and Therapy
Pyloric stenosis is treated with a surgery called a pyloromyotomy, with a baby asleep under anesthesia. In a pyloromyotomy, the outside of the pylorus muscle is cut to relieve the blockage. Prior to surgery, fluids and electrolytes will be given intravenously to correct the dehydration and electrolyte imbalances that are common in babies with pyloric stenosis. After the operation, fluids are given by vein until the baby can take all of his or her normal feedings by mouth. In infants who cannot safely be put to sleep for surgery, an endoscope with a camera and balloon may be used; the balloon can be inflated to widen the pylorus. Other options are tube feeding or medicine to relax the pylorus.
Prevention and Outcomes
There are no known ways of preventing pyloric stenosis, although it is possible that breast-feeding might reduce the risk.
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