Antley-Bixler syndrome with disordered steroidogenesis

What is Antley-Bixler Syndrome with Disordered Steroidogenesis?

Antley-Bixler syndrome with disordered steroidogenesis, also known as ABS1, is a rare genetic disorder characterized by skeletal malformations, genital anomalies, and hormonal imbalances. This condition is caused by mutations in the cytochrome P450 oxidoreductase gene, which plays a crucial role in the production of various hormones.

Key Features:

• Skeletal abnormalities, such as craniofacial deformities and radiohumeral synostosis (fusion of the radius and humerus bones)
• Genital anomalies, including ambiguous or undescended testes in males and vaginal atresia or other reproductive tract abnormalities in females
• Hormonal imbalances leading to cortisol deficiency, altered sex steroid synthesis, and infertility
• Severe cases may also present with Antley-Bixler syndrome-like features, such as midface hypoplasia and joint contractures

Causes and Prevalence:

ABS1 is a rare condition, and its exact prevalence is unknown. It is caused by homozygous or compound heterozygous mutations in the cytochrome P450 oxidoreductase gene. The disorder can be inherited in an autosomal recessive pattern.

Symptoms and Diagnosis:

The symptoms of ABS1 can vary widely among affected individuals, but may include:

• Skeletal deformities
• Genital anomalies
• Hormonal imbalances leading to cortisol deficiency and infertility
• Developmental delays or intellectual disability

Diagnosis is typically made through a combination of clinical evaluation, genetic testing (including sequencing of the cytochrome P450 oxidoreductase gene), and hormonal analysis.

Treatment and Management:

There is no cure for ABS1. Treatment focuses on managing the symptoms and complications associated with this condition. This may include:

• Hormone replacement therapy to address cortisol deficiency and other hormonal imbalances
• Surgical correction of skeletal deformities and genital anomalies
• Physical therapy to improve mobility and manage joint contractures

Prognosis:

The prognosis for individuals with ABS1 varies depending on the severity of their symptoms and the effectiveness of treatment. In general, affected individuals may experience significant morbidity and mortality due to complications associated with this condition.

References:

[4] Cortisol deficiency is usually partial, with some baseline cortisol production but failure to mount an adequate response to stress [4]. [14] The severe form of cytochrome P450

Based on the available information, it appears that Antley-Bixler syndrome (ABS) can present with a wide range of signs and symptoms, including:

• Skeletal abnormalities: Premature closure of skull bones (craniosynostosis), flattened midface (midface hypoplasia), nasal passage blockage (choanal atresia), and other skeletal anomalies [3].
• Genital differences: Hormonal changes in affected males and females can lead to the development of genital differences, as well as infertility [7].
• Other features: Midface hypoplasia, choanal stenosis or atresia, multiple joint contractures, visceral abnormalities, and obstructive sleep apnea are also commonly seen in ABS patients [6][8][9].

In addition to these physical symptoms, individuals with ABS may also experience hormonal changes that can affect their reproductive health. For example:

• Primary amenorrhea: Women with ABS may experience a failure to begin menstruation by age 16 (primary amenorrhea) [10].
• Infertility: Both males and females with ABS may experience infertility due to hormonal imbalances [7].

It's worth noting that the severity of these symptoms can vary widely among individuals with ABS, and some people may only experience mild cases. However, in general, ABS is a complex condition that requires comprehensive medical evaluation and management.

References:

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Diagnostic Tests for Antley-Bixler Syndrome with Disordered Steroidogenesis

Antley-Bixler syndrome with disordered steroidogenesis is a rare genetic disorder that affects the production of steroids in the body. Diagnostic tests are essential to confirm the diagnosis and rule out other conditions.

• Genetic Testing: Genetic testing is the primary diagnostic tool for Antley-Bixler syndrome with disordered steroidogenesis. It involves analyzing DNA samples from blood or saliva to identify mutations in the POR gene, which encodes cytochrome P450 oxidoreductase (CPR) [10][12].
• Sequence Analysis: Sequence analysis of the entire coding region is a type of genetic testing that can detect mutations in the POR gene [14].
• Next-Generation Sequencing (NGS): NGS, also known as massively parallel sequencing (MPS), is another type of genetic testing that can identify mutations in the POR gene [14].

Other Diagnostic Tests

In addition to genetic testing, other diagnostic tests may be conducted to confirm the diagnosis and assess the severity of the condition. These include:

• Imaging Procedures: Imaging procedures such as X-rays, CT scans, or MRI scans may be used to evaluate skeletal abnormalities and other physical characteristics associated with Antley-Bixler syndrome [12].
• Blood Tests: Blood tests can help determine the levels of steroids in the body and identify any hormonal imbalances [7].

Clinical Genetic Testing

Several clinical genetic testing options are available for Antley-Bixler syndrome with disordered steroidogenesis, including:

• Invitae Clinical Genetic Test: This test is offered by Invitae and covers conditions associated with Antley-Bixler syndrome, including genital anomalies and disordered steroidogenesis [2].
• Intergen Clinical Genetic Test: This test is offered by Intergen and includes genetic testing for Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis [5][8].

It's essential to consult a healthcare professional or a genetic counselor to discuss the diagnostic tests and determine the best course of action for each individual case.

Treatment Options for Antley-Bixler Syndrome with Disordered Steroidogenesis

Antley-Bixler syndrome (ABS) is a rare genetic disorder characterized by craniosynostosis, skeletal malformations, and disordered steroidogenesis. Individuals with ABS may experience various symptoms, including cortisol deficiency, genital anomalies, and other endocrine disorders.

Medication Management

For children with ABS who have genital anomalies and disordered steroidogenesis, medication changes are often necessary to manage the condition effectively [6]. Treatment typically involves a multidisciplinary approach, including early neurosurgical, pulmonary, and orthopedic management [5].

• Hydrocortisone: This medication is commonly used to treat cortisol deficiency in individuals with ABS. A case study reported that a patient with ABS caused by mutations in FGFR2 was treated with hydrocortisone and fludrocortisone [9].
• Fludrocortisone: This medication is also used to manage cortisol deficiency in individuals with ABS.

Surgical Intervention

In addition to medication management, surgical intervention may be necessary to treat the craniosynostosis and skeletal malformations associated with ABS. Treatment typically includes surgery to correct these abnormalities [8].

• Early neurosurgical management: Early surgical intervention is often necessary to prevent further complications and improve outcomes.
• Pulmonary and orthopedic management: Individuals with ABS may also require pulmonary and orthopedic management to address any related respiratory or musculoskeletal issues.

References

[5] - Treatment is symptomatic, and includes early neurosurgical as well as pulmonary and orthopedic management. This disorder is associated with a high risk of ... [6] - For children who have Antley-Bixler syndrome (ABS) with genital anomalies and disordered steroidogenesis, it is best to discuss medication changes with your ... [8] - In individuals with Antley–Bixler syndrome, treatment typically includes surgery. [9] - by H Woo · 2016 · Cited by 8 — We report here two cases of ABS caused by mutations in FGFR2 and POR . ... This patient has been treated with hydrocortisone and fludrocortisone.

Differential Diagnosis of Antley-Bixler Syndrome with Disordered Steroidogenesis

Antley-Bixler syndrome (ABS) is a rare genetic disorder characterized by craniosynostosis, skeletal malformations, and disordered steroidogenesis. When ABS is caused by changes to the POR gene, it is considered a disorder of steroidogenesis. In such cases, differential diagnosis with other conditions that present similar clinical features is essential.

Similar Clinical Picture

A similar clinical picture can be observed due to in utero environmental exposure to fluconazole, a lanosterol 14 alpha-demethylase inhibitor [6]. This condition can mimic the symptoms of ABS with disordered steroidogenesis. Therefore, it is crucial to consider this possibility when diagnosing ABS.

Other Conditions

Other conditions that may present similar clinical features include:

• Campomelic syndrome (see 114290): Although the differential diagnosis included campomelic syndrome, the exact relationship between these two conditions and ABS with disordered steroidogenesis is not well established [10].
• Other disorders of steroidogenesis: Deficient activities of multiple steroidogenic enzymes have been reported without and with Antley-Bixler syndrome (ABS), but mutations of specific genes are not specified [5].

Key Points

• ABS with disordered steroidogenesis caused by changes to the POR gene is a disorder of steroidogenesis.
• A similar clinical picture can be observed due to in utero environmental exposure to fluconazole.
• Other conditions, such as campomelic syndrome and other disorders of steroidogenesis, may present similar clinical features.

References

[5] CE Flück · 2004 · Cited by 532 — Deficient activities of multiple steroidogenic enzymes have been reported without and with Antley-Bixler syndrome (ABS), but mutations of specific genes are not specified. [6] A form of Antley-Bixler syndrome with normal steroidogenesis is a distinct disorder caused by mutation in the FGFR2 gene, but environmental exposure to fluconazole can mimic the symptoms of ABS with disordered steroidogenesis. [10] A form of Antley-Bixler syndrome that includes disordered steroidogenesis ... Although the differential diagnosis included campomelic syndrome (see 114290) ...