Antley–Bixler syndrome

A rare genetic disorder affecting bone and cartilage development

Antley–Bixler syndrome is a rare genetic disorder characterized by skeletal malformations and other systemic abnormalities. It is primarily associated with autosomal recessive inheritance patterns, although some cases may arise from autosomal dominant mutations. The syndrome is named after Dr. Ray M. Antley and Dr. David Bixler, who first described the condition.

Clinical Features

Antley–Bixler syndrome presents with a variety of clinical features, which can vary in severity among affected individuals. Common characteristics include:

• Craniosynostosis: Premature fusion of the skull bones, leading to an abnormal head shape.
• Midface hypoplasia: Underdevelopment of the midfacial region, often resulting in a flattened appearance.
• Radiohumeral synostosis: Fusion of the radius and humerus bones in the arm, limiting movement.
• Femoral bowing: Abnormal curvature of the femur, or thigh bone.
• Joint contractures: Stiffness and limited range of motion in the joints.
• Genital abnormalities: Ambiguous genitalia or underdeveloped genital structures.

Genetics

Antley–Bixler syndrome is most commonly associated with mutations in the FGFR2 gene, which encodes the fibroblast growth factor receptor 2. This gene plays a crucial role in bone development and growth. Mutations in the POR gene, which is involved in steroidogenesis and drug metabolism, have also been implicated in some cases.

Diagram of autosomal recessive inheritance pattern

The condition can be inherited in an autosomal recessive manner, meaning that an affected individual must inherit two copies of the mutated gene, one from each parent. In some cases, autosomal dominant inheritance has been observed, where a single copy of the mutated gene can cause the disorder.

Diagnosis

Diagnosis of Antley–Bixler syndrome is based on clinical evaluation, family history, and genetic testing. Imaging studies, such as X-rays and CT scans, are used to assess skeletal abnormalities. Genetic testing can confirm mutations in the FGFR2 or POR genes.

Management

Management of Antley–Bixler syndrome is multidisciplinary, involving specialists in orthopedics, genetics, endocrinology, and plastic surgery. Treatment focuses on addressing specific symptoms and may include:

• Surgical correction of craniosynostosis and other skeletal deformities.
• Hormonal therapy for endocrine abnormalities.
• Physical therapy to improve joint mobility and muscle strength.

Prognosis

The prognosis for individuals with Antley–Bixler syndrome varies depending on the severity of the symptoms and the presence of associated complications. Early intervention and comprehensive management can improve quality of life and functional outcomes.

Related pages

• Craniosynostosis
• Genetic disorders
• Skeletal dysplasia