Antley-Bixler syndrome

Antley-Bixler syndrome (ABS) is a rare congenital disorder characterized by craniosynostosis (premature fusion of skull bones), radiohumeral synostosis (fusion of the forearm bones at the elbow), bowing of the thighbones (femoral bowing), midface hypoplasia, and other skeletal anomalies. The condition affects multiple body systems, most prominently the skeletal system, craniofacial structures, and in some cases the urogenital and endocrine systems. Key clinical features include a distinctive facial appearance with a flattened midface, depressed nasal bridge, proptosis (bulging eyes), choanal atresia or stenosis (narrowing or blockage of the nasal passages), joint contractures, long bone fractures, and arachnodactyly (long, slender fingers). Antley-Bixler syndrome has two recognized genetic forms. One form is caused by autosomal dominant gain-of-function mutations in the FGFR2 gene (fibroblast growth factor receptor 2), which primarily affects skeletal development without significant genital anomalies or steroidogenic defects. The second form is autosomal recessive and is caused by loss-of-function mutations in the POR gene (cytochrome P450 oxidoreductase), which encodes an enzyme essential for steroid biosynthesis. Patients with POR mutations often present with ambiguous genitalia or disordered sex development in addition to the skeletal features, due to impaired steroidogenesis. Some cases historically attributed to Antley-Bixler syndrome have also been associated with maternal fluconazole exposure during pregnancy. Treatment is supportive and multidisciplinary. Surgical intervention may be required for craniosynostosis to relieve intracranial pressure, for choanal atresia to establish adequate airway patency, and for skeletal deformities. Patients with POR deficiency may require hormone replacement therapy, particularly cortisol supplementation during physiological stress. Long-term management involves orthopedic care, developmental monitoring, and endocrine follow-up as needed. Prognosis varies depending on the severity of the malformations, with some severely affected neonates experiencing life-threatening respiratory complications.

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