Evidence that FGFRL1 contributes to congenital diaphragmatic hernia development in humans

Fibroblast growth factor receptor-like 1 (FGFRL1) encodes a transmembrane protein that is related to fibroblast growth factor receptors but lacks an intercellular tyrosine kinase domain. in vitro studies suggest that FGFRL1 inhibits cell proliferation and promotes cell differentiation and cell adhesion. Mice that lack FGFRL1 die shortly after birth from respiratory distress and have abnormally thin diaphragms whose muscular hypoplasia allows the liver to protrude into the thoracic cavity. Haploinsufficiency of FGFRL1 has been hypothesized to contribute to the development of congenital diaphragmatic hernia (CDH) associated with Wolf-Hirschhorn syndrome. However, data from both humans and mice suggest that disruption of one copy of FGFRL1 alone is insufficient to cause diaphragm defects. Here we report a female fetus with CDH whose 4p16.3 deletion allows us to refine the Wolf-Hirschhorn syndrome CDH critical region to an approximately 1.9 Mb region that contains FGFRL1. We also report a male infant with isolated left-sided diaphragm agenesis who carried compound heterozygous missense variants in FGFRL1. These cases provide additional evidence that deleterious FGFRL1 variants may contribute to the development of CDH in humans

Population-based incidence of injuries among preschoolers.

A population survey was conducted to determine the incidence of injuries among preschoolers and their risk factors. A systematic sample (15%, n = 4540) of families with at least one child aged 0-5 years in 1991 living in the Canton of Vaud (Switzerland) received a mailed questionnaire in February 1992. There were 5827 eligible children in the sample. The response rate was 67.5% after two recall mailings. Injuries were defined as those from all causes with at least one physician contact in 1991. The overall incidence was 224 injuries per 1000 children (95% CI [= confidence intervall]: 211-237); 188 per 1000 children were injured over 1 year (95% CI: 176-200, n = 746), of whom 16.5% (n = 123) had 32 injuries. Falls represented 66% of all injuries, followed by burns (8%) and poisonings (5%). The proportion of hospitalized cases was 4.8% and the population incidence of hospitalization due to injury was 10.8/1000 children. Socioeconomic factors did not influence the occurrence of injuries. CONCLUSION: The measured incidence of injuries among preschoolers is among the highest in developed countries. Practitioners could contribute more effectively to injury prevention through routine information and counselling of parents from all social backgrounds