Isolated hypertrophic pyloric stenosis and perinatal factors

Infantile hypertrophic pyloric stenosis (IHPS) is a common condition requiring surgical intervention during the first weeks of life. Up to now the exact etiology of IHPS remains unclear and it is probable that several predisposing risk factors would be associated with the condition. Prompted by the observation that some perinatal factors may be involved in IHPS etiology, we evaluated 171 isolated cases referred to the Sicilian Registry of Congenital Anomalies. Our results show that some perinatal factors like sex ratio imbalance and parity are associated with IHPS, but further investigation is needed to clarify the relationship between genes and other factors involved in IHPS etiology. Therefore the presence of these perinatal factors may be accurately evaluated in genetic counseling to provide a perspective of recurrence prevention.     

The association of sex ratio anomalies with pyloric stenosis

Published family data were examined for evidence of aberrant sex ratios in relatives of pyloric stenosis index cases. An excess of males over females was found among unaffected members of sibships in which there occurred more than one case of pyloric stenosis. The male excess among affected members of these sibships did not differ from that among index cases without affected sibs. An unusual frequency of spontaneous abortions in these subships, which might account for the observed excess of males, was not observed. No evidence was found of sex ratio anomalies in other classes of relative of pyloric stenosis index cases, whether or not the index cases had affected sibs.     

Incidence of infantile hypertrophic pyloric stenosis in Saskatchewan, 1970-85.

We reviewed the incidence rates of infantile hypertrophic pyloric stenosis (IHPS) and pylorospasm in Saskatchewan from 1970 to 1985 and found a marked decrease in the rates after 1976. As expected, there was a preponderance of males among those with IHPS and among those with pylorospasm discharged from hospital between 1 and 3 months of age. No seasonal pattern was observed. We believe that the decrease in incidence rates was related to environmental influences, such as changes in the methods of feeding observed since 1977.     

Infantile hypertrophic pyloric stenosis: a study of feeding practices and other possible causes.

We carried out a case-control study of the hospital charts of 91 infants with infantile hypertrophic pyloric stenosis (IHPS) to determine the feeding practices at the time of discharge from the neonatal nursery. We excluded infants whose feeding might have been influenced by confounding factors. The infants were matched with controls for gestational age. The mean birth weight of the IHPS group was 3501 g and of the control group 3543 g. The male:female ratio for the IHPS group was 5.5. The odds ratio of male predominance was 4. We found that bottle-feeding was 2.9 times more prevalent among the infants with IHPS than among the control subjects. We speculate that the recently observed decrease in the incidence of IHPS is due to the decline in bottle-feeding.     

Linkage of monogenic infantile hypertrophic pyloric stenosis to chromosome 16p12-p13 and evidence for genetic heterogeneity

Infantile hypertrophic pyloric stenosis (IHPS) is the most common form of bowel obstruction in infancy. The disease affects males four times more often than females and is considered a paradigm for the sex-modified model of multifactorial inheritance. However, pedigrees consistent with autosomal dominant inheritance have also been documented. We analyzed a 3-generation family with IHPS including 10 affected individuals (5 males and 5 females) and mapped the underlying disease locus to chromosome 16p12-p13 (LOD score 3.23) by using a single-nucleotide polymorphism-based genomewide scan. The analysis of 10 additional multiplex pedigrees yielded negative or nonsignificant LOD scores, indicating the presence of locus heterogeneity. Sequence analysis of candidate genes from the chromosome 16 disease interval excluded the presence of pathogenic mutations in the GRIN2A and MYH11 genes.     

Epidemiological features of infantile hypertrophic pyloric stenosis in Taiwanese children: a Nation-Wide Analysis of Cases during 1997-2007

Objective

To describe the epidemiological characteristics of infantile hypertrophic pyloric stenosis (IHPS) in ethnic Chinese children.

Materials and Methods

We reviewed the National Health Insurance claims database and analyzed data from children less than one year of age who had been diagnosed with IHPS (ICD-9-CM 750.5) and had undergone pyloromyotomy (ICD-9-CM 43.3). We analyzed the incidence, gender, age at diagnosis, length of hospital stay, seasonal variation and cost of IHPS from data collected between January 1997 and December 2007.

Results

A total of 1,077 infants met inclusion criteria, including 889 boys and 188 girls. The annual incidence of IHPS ranged from 0.30 to 0.47 per 1,000 live births with a mean incidence of 0.39 per 1,000 live births. Between 2002 and 2007, the incidence showed a declining trend (P = 0.025) with coincidentally increasing trends for both exclusive breastfeeding (P = 0.014) and breastfeeding plus bottle feeding (P = 0.004). The male-to-female rate ratio was dynamic and increased from 3.03 during the first two weeks of life to 8.94 during the 8^th through 10^thweeks of life. The overall male-to-female rate ratio was 4.30. The mean age at diagnosis was 43.1±2.4 days. After analyzing the months of birth and hospital admission, no seasonal variation associated with IHPS was detected. The mean length of hospital stay was 8.28±7.10 days.

Conclusions

The incidence of IHPS in Taiwan, a country with a majority ethnic Chinese population, was lower than observed incidences in Caucasian populations living in Western countries. Breastfeeding campaigns and low maternal smoking rates may contribute to the lower incidence of IHPS in Taiwan. However, additional studies with longer follow-up periods are needed.     

Genome-wide high-density SNP-based linkage analysis of infantile hypertrophic pyloric stenosis identifies loci on chromosomes 11q14-q22 and Xq23

Infantile hypertrophic pyloric stenosis (IHPS) has an incidence of 1-8 per 1000 live births and is inherited as a complex sex-modified multifactorial trait with a striking male preponderance. Syndromic and monogenic forms exist, and two loci have been identified. Infants present with vomiting due to gastric-outlet obstruction caused by hypertrophy of the smooth muscle of the pylorus. A genome-wide SNP-based high-density linkage scan was carried out on 81 IHPS pedigrees. Nonparametric and parametric linkage analysis identified loci on chromosomes 11q14-q22 (Z(max) = 3.9, p < 0.0001; HLOD(max) = 3.4, alpha = 0.34) and Xq23 (Z(max) = 4.3, p < 0.00001; HLOD(max) = 4.8, alpha = 0.56). The two linked chromosomal regions each harbor functional candidate genes that are members of the canonical transient receptor potential (TRPC) family of ion channels and have a potential role in smooth-muscle control and hypertrophy.