An inherited syndrome with craniofacial dysmorphism and skeletal and other anomalies. It is frequently associated with respiratory failure in the neonatal period.
Multisynostotic Osteodysgenesis with Long Bone Fractures; Trapezoidocephaly-Synostosis Syndrome.
First description in 1974 by the French physicians M. Lacheretz, R. Walbaum, and C. Tourgis, but named after Ray M. Antley and David Bixler, the two American physicians who described a similar case in 1975.
The incidence is unknown, but to date probably approximately 50 cases have been described.
Autosomal recessive, but few cases may be sporadic or transmitted as an autosomal dominant trait or show digenic inheritance. Parental consanguinity is considered a risk factor. The ratio of affected females to males is approximately 7:2. The flavoprotein POR (cytochrome P-450 oxidoreductase) transfers electrons from reduced nicotinamide adenine dinucleotide phosphate (NADPH) to all microsomal cytochrome P450 (CYPP450) enzymes. The human genome contains over 50 genes for CYPP450 enzymes with the vast majority of them encoding microsomal CYPP450s, including at least 15 genes encoding hepatic drug-metabolizing CYPP450s and at least 20 genes encoding CYPP450s that are involved in the biosynthesis of cholesterol, steroid hormones, and fatty acids. All these microsomal enzymes require POR as a catalyst and mutations in the POR gene can be demonstrated in patients with Antley-Bixler Syndrome (ABS). The lack or malfunction of POR can lead to accumulation of drugs and environmental toxins usually metabolized by hepatic CYPP450. For some drugs, this may result in levels high enough to cause teratogenicity with fluconazole being one drug that has been implicated in the pathogenesis of ABS. This autosomal recessive inherited defect has been mapped to chromosome 7q.11.23. The role of mutations in the Fibroblast Growth Factor Receptor 2 (FGFR-2) gene, which has been mapped to chromosome 10q26.13 and was initially suspected to be the cause of this disorder, is now considered to be responsible for the autosomal recessive inherited variant of ABS without anomalies of the steroidogenesis or the genitals. The anomalies in steroid biosynthesis seem to be at least in part responsible for the genital anomalies found in female patients.
Based on the clinical findings of trapezoidocephaly and multiple skeletal fusions. The craniofacial anomalies may result in severe upper airway obstruction that can lead to death secondary to respiratory failure already in the first days or weeks of life in approximately 50% of cases. The overall early mortality has been reported to be as high as 80%.
Multiple malformations predominately involve the head with craniosynostosis (typically coronal), brachy- or trapezoidocephaly, large anterior fontanelle, frontal bossing, shallow orbits, severe midface hypoplasia, small bulbous nose with anteverted nares and low nasal bridge, choanal atresia, ...