Early pyloric stenosis: a case control study

Pyloric stenosis (PS) is rare in the first 2 weeks of life, often leading to delays in diagnosis and treatment. We conducted a case control study to delineate the characteristics of patients with early PS (EPS). In addition, we tested the hypothesis that patients with EPS present with a smaller pylorus than older patients. A database of all patients presenting with PS to a children’s hospital over a 5-year period (2002–2006) was obtained. Each patient admitted during the first 2 weeks of life (subject) was matched to a patient admitted after 4 weeks of age (control), with the same gender, electrolyte status, and treating surgeon. A single pediatric radiologist, blinded to patient age, reviewed all available ultrasounds retrospectively. Demographic, clinical, diagnostic, therapeutic, and outcome data were compared. During the study period, 278 pyloromyotomies were performed for PS. Sixteen patients (5.8%) presented with EPS between 2 and 14 days of life. EPS patients had a higher prevalence of positive family history (31 vs. 0%, P = 0.043), and breast milk feeding (75 vs. 31%, P = 0.045). Sonographic measurements showed a pylorus that was of significantly less length (17.1 ± 0.6 vs. 20.5 ± 0.9 mm, P = 0.006) and muscle thickness (3.5 ± 0.2 vs. 4.9 ± 0.2 mm, P < 0.001) in patients with EPS. Hospital stay was significantly longer for EPS patients (4.3 ± 0.9 vs. 2.0 ± 0.1 days, P = 0.19) Babies presenting with EPS are more likely to be breast fed and to have a positive family history. EPS is associated with a longer hospital stay. Use of sonographic diagnostic measurements specific to this age group may prevent delays in diagnosis and treatment, and improve outcomes

A novel missense mutation in the transcription factor FOXF1 co-segregating with infantile hypertrophic pyloric stenosis in the extended pedigree linked to IHPS5 on chromosome 16q24.

BACKGROUND: The aim was to identify susceptibility alleles for infantile hypertrophic pyloric stenosis (IHPS) in a pedigree previously linked to IHPS5 on chromosome 16q24. METHODS: We screened the positional and functional candidate gene FOXF1 by Sanger sequencing in a single affected individual. All family members for whom DNA was available were genotyped to determine co-segregation status of the putative causal variant. Immunofluorescence studies were performed to compare the cellular localisation of wildtype and mutant form of the protein. Transcriptional activity was compared using a luciferase assay. RESULTS: A single novel substitution in FOXF1 (c.416G>A) predicted to result in a missense mutation (R139Q) was shown to co-segregate with disease trait. It was not seen in 560 control chromosomes nor has it been reported in ExAC or ESP. The R139Q substitution affects a conserved arginine residue within the DNA-binding domain of FOXF1. The transcriptional activity of the mutant FOXF1 protein is significantly reduced in comparison to wild-type. CONCLUSION: These results provide strong evidence that the R139Q substitution in FOXF1 causes IHPS in this family and imply a novel pathological pathway for the condition. They further support a role for FOXF1 in the regulation of embryonic and neonatal development of the gastro-intestinal tract