Antley-Bixler syndrome

Two distinct molecular forms with overlapping phenotype:

• POR-related Antley-Bixler (autosomal recessive): POR (P450 oxidoreductase). Causes both the skeletal phenotype AND the disordered steroidogenesis (genital ambiguity, maternal virilization in pregnancy).
• FGFR2-related Antley-Bixler (autosomal dominant): FGFR2 missense mutations. Skeletal phenotype only; steroidogenesis is normal.

The molecular distinction matters for endocrine workup and recurrence risk.

• Craniosynostosis: most often coronal, producing brachycephaly/trapezoidocephaly
• Midface hypoplasia with severe airway compromise; choanal atresia common
• Radiohumeral synostosis: elbows fixed in flexion (pathognomonic combo with craniosynostosis)
• Femoral bowing and other long-bone bowing
• Genital anomalies in POR form: under-virilized 46,XY males or virilized 46,XX females; maternal virilization during pregnancy
• Disordered steroidogenesis in POR form: combined 17α-hydroxylase/17,20-lyase + 21-hydroxylase deficiency picture

• Clinical: craniosynostosis + radiohumeral synostosis is highly characteristic
• 3D CT skull and skeletal survey
• Steroid profile (urinary steroids, ACTH stimulation) to distinguish POR from FGFR2 form
• Sequencing of POR and FGFR2

• Pfeiffer syndrome: craniosynostosis + broad thumbs/toes, no radiohumeral synostosis, FGFR1/2
• Crouzon syndrome: craniosynostosis + midface hypoplasia, normal limbs
• Apert syndrome: craniosynostosis + syndactyly; no radiohumeral fusion

• Airway: the major early-life concern; tracheostomy may be needed for choanal atresia and midface obstruction
• Cranial vault reconstruction in infancy
• Endocrine (POR form): hydrocortisone replacement; sex assignment counseling
• Orthopedic: elbow contracture management
• Neurosurgery + craniofacial team as a multidisciplinary unit
• Genetic counseling depends on molecular form (POR = AR, ~25% recurrence; FGFR2 = AD, often de novo)