FREM1 and congenital diaphragmatic hernia: FREM1 protein belongs to the FRAS1/FREM family of extracellular matrix proteins which localizes at the basement membranes and forms a ternary complex including FRAS1, FREM1 and FREM2. Recessive mutations in FREM1 have been described to cause congenital diaphragmatic hernia and two rare syndromes—bifid nose with or without anorectal and renal anomalies syndrome (BNAR; OMIM #608,980) and Manitoba oculotrichoanal syndrome (MOTA; OMIM #248,450)—whose phenotypic characteristics overlap those seen in individuals with Fraser syndrome [8].