Infantile hypertrophic pyloric stenosis—genetics and syndromes

Abstract

Infantile hypertrophic pyloric stenosis (IHPS) is a common condition in neonates that is characterized by an acquired narrowing of the pylorus. The aetiology of isolated IHPS is still largely unknown. Classic genetic studies have demonstrated an increased risk in families of affected infants. Several genetic studies in groups of individuals with isolated IHPS have identified chromosomal regions linked to the condition; however, these associations could usually not be confirmed in subsequent cohorts, suggesting considerable genetic heterogeneity. IHPS is associated with many clinical syndromes that have known causative mutations. Patients with syndromes associated with IHPS can be considered as having an extreme phenotype of IHPS and studying these patients will be instrumental in finding causes of isolated IHPS. Possible pathways in syndromic IHPS include: (neuro)muscular disorders; connective tissue disorders; metabolic disorders; intracellular signalling pathway disturbances; intercellular communication disturbances; ciliopathies; DNA-repair disturbances; transcription regulation disorders; MAPK-pathway disturbances; lymphatic abnormalities; and environmental factors. Future research should focus on linkage analysis and next-generation molecular techniques in well-defined families with multiple affected members. Studies will have an increased chance of success if detailed phenotyping is applied and if knowledge about the various possible causative pathways is used in evaluating results.

Stomach development, stem cells and disease

“…Among the congenital disorders that represent aberrant stomach development, infantile hypertrophic pyloric stenosis ( pyloric stenosis) is the most common, with an incidence of 2-4 cases per 1000 live births. The condition is caused by muscle hypertrophy, which narrows the pyloric canal and creates functional gastric outlet obstruction (Peeters et al, 2012). Pyloric stenosis is in fact a complex disorder influenced by genetic and environmental factors, including maternal smoking and alcohol use.…”

Infantile hypertrophic pyloric stenosis (IHPS): A study of its pathophysiology utilizing the newborn hph-1 mouse model of the disease

“…The IHPS etiology and pathogenesis are unknown, but the increased sphincter tone is believed to be related to reduced pyloric tissue nNOS expression (2) and the resulting lower NO generation (13,34,45). Several experimental animal models of the condition have been studied, but the hyperphenylalaninemia-1 (hph-1) newborn mouse is the one that most closely reflects the human IHPS phenotype.…”

“…Infantile hypertrophic pyloric stenosis (IHPS) is a relatively common disease affecting 2 in 1,000 live births (34) and manifesting clinically at 3-6 wk of age. The IHPS etiology and pathogenesis are unknown, but the increased sphincter tone is believed to be related to reduced pyloric tissue nNOS expression (2) and the resulting lower NO generation (13,34,45).…”

Tetrahydrobiopterin deficiency induces gastroparesis in newborn mice

“…Infants with this condition seldom exhibit any abnormalities at birth. The gastric outlet obstruction develops at 2-12 wk of life, and the pyloric sphincter hypertrophy quickly resolves after pyloromyotomy, a surgical intervention involving the longitudinal incision of the circular muscle (23,27,28).IHPS has traditionally been seen as a condition resulting from failure of the pyloric sphincter muscle to relax, thus preventing adequate and rapid gastric emptying following a meal. Infants with IHPS have a lower plasma nitrate level when compared with age-matched controls, and, following pyloromyotomy, the nitrate concentration increases to values found in normal infants (17).…”

“…Infants with this condition seldom exhibit any abnormalities at birth. The gastric outlet obstruction develops at 2-12 wk of life, and the pyloric sphincter hypertrophy quickly resolves after pyloromyotomy, a surgical intervention involving the longitudinal incision of the circular muscle (23,27,28).…”