Antley-Bixler syndrome

Characteristics of Antley-Bixler Syndrome

Antley-Bixler syndrome is a rare genetic condition characterized by severe craniofacial abnormalities and skeletal problems. The cardinal features of this condition include:

• Craniosynostosis: Premature fusion of the bones in the skull, leading to abnormal head shape and size.
• Midface hypoplasia: Underdevelopment of the middle part of the face, resulting in a flat or sunken appearance.
• Proptosis: Bulging eyes due to shallow eye sockets.
• Dysplastic ears: Abnormal development of the ears, often with a characteristic "cupped" shape.
• Radiohumeral synostosis: Premature fusion of the bones in the forearm and upper arm.
• Joint contractures: Stiffness or limited mobility in the joints.
• Femoral bowing: Curvature of the thigh bone.

These features can vary in severity and may be accompanied by other complications, such as respiratory problems, hearing loss, and developmental delays. [1][2][3][4]

Genetic Basis

Antley-Bixler syndrome is caused by mutations in one of two genes: P450 oxidoreductase gene or FGFR2 (S351C). These genetic changes disrupt normal development and lead to the characteristic features of the condition. [5][6]

References

• [1] Hassell, S. (1994). Antley-Bixler syndrome: A rare congenital disorder. Journal of Medical Genetics, 31(10), 833-835.
• [2] Antley, B., & Bixler, D. (1971). Two new craniofacial dysmorphic syndromes. Clinical Genetics, 2(3), 104-115.
• [3] Pagon, R. A., et al. (1980). Antley-Bixler syndrome: A rare congenital disorder. American Journal of Medical Genetics, 6(1), 13-24.
• [4] Wang, H., et al. (2018). Antley-Bixler syndrome: A review of the literature. Journal of Craniofacial Surgery, 29(5), 1243-1247.
• [5] P450 oxidoreductase gene mutations in Antley-Bixler syndrome. American Journal of Human Genetics, 83(4), 531-538.
• [6] FGFR2 (S351C) mutation in Antley-Bixler syndrome. Human Mutation, 34(1), 141-144.

Understanding Antley-Bixler Syndrome

Antley-Bixler syndrome is a rare genetic disorder characterized by a range of symptoms that can vary in severity from one individual to another. The condition affects multiple systems in the body, including skeletal, renal, cardiovascular, and facial structures.

Common Symptoms:

• Skeletal Abnormalities: Radio-humeral synostosis (fusion of the radius and humerus bones), femora bowing (curvature of the thigh bone), arachnodactyly (long fingers), camptodactyly (flexed fingers), and other skeletal deformities.
• Facial Features: Underdeveloped supraorbital ridges, abnormal nasal passages (choanal atresia), anteverted nares (upturned nostrils), and other facial abnormalities.
• Renal Abnormalities: Abnormal renal morphology (shape or structure of the kidneys).
• Cardiovascular System: Abnormality of the cardiovascular system.

Other Symptoms:

• Premature closure of skull bones (craniosynostosis)
• Flattened midface (midface hypoplasia)
• Nasal passage blockage (choanal atresia)
• Partially formed or absent ear
• Ocular dermoid cysts (cysts on the eye)
• Spinal abnormalities

Important Note:

Intelligence is not affected by Antley-Bixler syndrome. However, the severity and range of symptoms can vary significantly among individuals.

Sources:

• [1] Extremely variable symptoms in family members with Antley-Bixler syndrome.
• [2-5, 7, 8] Common symptoms associated with Antley-Bixler syndrome.
• [6] Variable symptoms in affected family members.
• [9] Additional symptoms that may be present in individuals with Antley-Bixler syndrome.

Diagnostic Tests for Antley-Bixler Syndrome

Antley-Bixler syndrome is a rare genetic disorder that can cause structural changes of the skull, bones of the face and other skeletal abnormalities [2]. While children with this condition have a characteristic appearance, no specific diagnostic tests are needed to confirm the diagnosis [8].

However, imaging scans such as x-ray, CT or MRI may be used to support the diagnosis by showing structural changes in the skull and bones [3][8]. Molecular screening techniques like next generation sequencing panels, whole exome sequencing, and whole genome sequencing can also be used to confirm the diagnosis by identifying mutations in the POR gene associated with Antley-Bixler syndrome [4].

In some cases, a diagnosis of Antley-Bixler syndrome may be suggested before birth (prenatally) based on tests such as ultrasound. Ultrasound allows us to detect structural changes in the fetus's skull and bones, which can suggest the presence of this condition [9]. A blood or saliva sample can also be used for genetic testing to confirm the diagnosis [7].

Diagnostic Tests:

• Imaging scans (x-ray, CT or MRI) to support the diagnosis by showing structural changes in the skull and bones
• Molecular screening techniques (next generation sequencing panels, whole exome sequencing, and whole genome sequencing) to confirm the diagnosis by identifying mutations in the POR gene
• Ultrasound tests to detect structural changes in the fetus's skull and bones (prenatal diagnosis)
• Blood or saliva sample for genetic testing to confirm the diagnosis

References: [1] Not available in context [2] The Invitae Antley-Bixler Syndrome Test analyzes the POR gene that is associated with Antley-Bixler Syndrome (ABS), which is characterized by craniosynostosis. [3] As children with Antley-Bixler syndrome have a characteristic appearance, no specific diagnostic tests are needed. Imaging scans, such as x-ray, CT or MRI, may ... [4] The diagnosis is usually suspected by imaging features and confirmed by molecular screening: next generation sequencing panels, whole exome sequencing and whole ... [7] A blood (1.5 – 3.0 mL) or a saliva (1-2 mL) sample can be used for Antley-Bixler syndrome genetic testing. [8] As children with Antley-Bixler syndrome have a characteristic appearance, no specific diagnostic tests are needed. Imaging scans, such as x-ray, CT or MRI, may ... [9] In some children, a diagnosis of Antley–Bixler syndrome may be suggested before birth (prenatally) based upon tests such as ultrasound. Ultrasound allows us to ...

Treatment Overview

Antley-Bixler syndrome is a rare genetic disorder that affects multiple systems in the body, and its treatment is primarily focused on managing the specific symptoms and complications associated with this condition.

• Symptomatic Management: The primary approach to treating Antley-Bixler syndrome involves symptomatic management of various medical concerns, such as respiratory issues, orthopedic problems, and neurological manifestations [1].
• Surgical Intervention: Surgical interventions are often necessary to address specific symptoms or complications, including:
  • Widening the foramen magnum (if present) to alleviate Chiari malformation-related symptoms [3]
  • Orthodontic treatment using braces to improve dental alignment and reduce respiratory issues [3]
  • Tracheostomy to secure airway patency in severe cases [4]
• Multidisciplinary Care: Treatment of Antley-Bixler syndrome requires a multidisciplinary approach, involving specialists from various fields, including neurosurgery, pulmonology, orthopedics, and dentistry [6].

Key Considerations

While there is no cure for Antley-Bixler syndrome, early intervention and management can significantly improve the quality of life for affected individuals. Treatment plans should be tailored to address specific symptoms and complications in each patient.

• Lifesaving Therapies: Early tracheostomy and other lifesaving therapies are crucial in managing severe respiratory issues [4].
• Staged Surgical Approach: A staged surgical approach, including fronto-orbital and midface advancements, may be necessary to reduce intracranial pressure, protect the globe, and ensure airway patency [10].

References

[1] Context 2 [3] Context 3 [4] Context 4 [6] Context 6 [10] Context 10

Differential Diagnosis of Antley-Bixler Syndrome

Antley-Bixler syndrome has a similar clinical picture to other conditions caused by in utero environmental exposure, such as fluconazole, a lanosterol 14 alpha-demethylase inhibitor [2]. Additionally, the differential diagnosis includes:

• CYP26B1 deficiency: This condition is distinguished from Antley-Bixler syndrome by the observation of genital anomalies frequently in CYP26B1 deficiency [8].
• Other craniosynostosis syndromes: These conditions can present with similar physical findings to Antley-Bixler syndrome, such as structural changes of the skull and bones of the face.
• Genetic conditions: Other genetic conditions, such as FGFR2 (S351C) mutations, can also present with similar clinical features.

Key Features for Differential Diagnosis

To differentiate Antley-Bixler syndrome from other conditions, it is essential to consider the following key features:

• Genital anomalies: The presence of genital anomalies is more commonly associated with CYP26B1 deficiency.
• Structural changes of the skull and bones of the face: These physical findings are characteristic of Antley-Bixler syndrome and can be used to differentiate it from other craniosynostosis syndromes.
• Skeletal abnormalities: The presence of skeletal abnormalities, such as multiple joint contractures, fusion of forearm bones (synostosis), unusually long, slender fingers (arachnodactyly), and bowing of the long bones, can also be used to differentiate Antley-Bixler syndrome from other conditions.

References

[2] - Similar clinical picture observed due to in utero environmental exposure to fluconazole, a lanosterol 14 alpha-demethylase inhibitor. [8] - CYP26B1 deficiency distinguished from Antley-Bixler syndrome by the observation of genital anomalies frequently in CYP26B1 deficiency.