autosomal dominant craniometaphyseal dysplasia

Autosomal Dominant Craniometaphyseal Dysplasia (AD-CMD) Overview

Autosomal dominant craniometaphyseal dysplasia (AD-CMD) is a rare genetic disorder characterized by the progressive thickening and increased mineral density of craniofacial bones. This condition is inherited in an autosomal dominant manner, meaning that only one copy of the mutated gene is required to express the disease.

Key Features:

• Inheritance Pattern: AD-CMD is inherited in an autosomal dominant pattern, where a single copy of the mutated gene is sufficient to cause the condition.
• Craniofacial Bone Abnormalities: The disorder is characterized by progressive thickening and increased mineral density of craniofacial bones, leading to various facial deformities.
• Rare Disorder: AD-CMD is a very rare disorder, with its incidence unknown.

Causes:

• Genetic Mutation: Mutations in the ANKH gene are known to cause autosomal dominant craniometaphyseal dysplasia (AD-CMD).

References:

• [1] by E Reichenberger · 2020 · Cited by 8 — By definition, autosomal dominant craniometaphyseal dysplasia (AD-CMD) is inherited in an autosomal dominant manner.
• [2] Aug 27, 2007 — By definition, autosomal dominant craniometaphyseal dysplasia (AD-CMD) is inherited in an autosomal dominant manner.
• [5] Causes. Mutations in the ANKH gene cause autosomal dominant craniometaphyseal ...
• [9] by E Reichenberger · 2001 · Cited by 217 — Craniometaphyseal dysplasia (CMD) is a rare skeletal disorder characterized by progressive thickening and increased mineral density of craniofacial bones ...

Autosomal dominant craniometaphyseal dysplasia (CMD) is a rare genetic disorder characterized by the overgrowth of bones in the head, arms, and legs. The signs and symptoms of CMD can vary from person to person, but here are some common manifestations:

• Overgrowth of bones: The most distinctive feature of CMD is the abnormal growth of bones in the head, arms, and legs [1]. This can lead to a range of complications, including:
  • Widely spaced eyes (hypertelorism) [6]
  • Distorted facial features [7]
  • Asymmetry of the mandible (jawbone) [8]
• Compression of cranial nerves: The overgrowth of bones in the head can compress the cranial nerves, leading to a range of symptoms, including:
  • Paralysis of the facial muscles (facial nerve palsy) [2][7][9]
  • Hearing loss [4][8]
  • Blindness [2]
• Other complications: CMD can also lead to other complications, such as:
  • Delayed teething [7]
  • Breathing or feeding problems [7]
  • Sclerosis of the skull (hardening of the bones) [1][8]

It's worth noting that the symptoms of CMD can vary in severity and may not be present at birth. In some cases, the condition may only become apparent during childhood or adolescence.

References:

[1] Context 3 [2] Context 2 [4] Context 4 [6] Context 6 [7] Context 7 [8] Context 8 [9] Context 9

Autosomal dominant craniometaphyseal dysplasia (AD-CMD) can be diagnosed through a combination of clinical evaluation, radiographic findings, and genetic testing.

Clinical Evaluation

The diagnosis of AD-CMD is often based on the presence of characteristic clinical features, including:

• Wide nasal bridge
• Paranasal bossing
• Widely spaced eyes with an increase in bizygomatic width
• Prominent mandible
• Delayed development of dentition and failure to erupt teeth [11][13]

Radiographic Findings

X-rays or other imaging studies are often required to confirm the diagnosis of AD-CMD. These may show:

• Diffuse hyperostosis of cranial bones
• Unusually shaped long bones, particularly in the legs [7]
• Abnormalities in the metaphyses and diaphyses of long bones

Genetic Testing

Genetic testing can also help diagnose AD-CMD by identifying mutations in the ANKH gene (605145) on chromosome 5p15. This is a heterozygous mutation, meaning that only one copy of the mutated gene is needed to cause the condition [3].

Diagnostic Tests

The following diagnostic tests may be used to confirm the diagnosis of AD-CMD:

• X-rays or other imaging studies
• Genetic testing (ANKH gene)
• Blood samples and tissue samples for molecular analysis

It's worth noting that a combination of clinical evaluation, radiographic findings, and genetic testing is often required to confirm the diagnosis of AD-CMD.

References: [3] Craniometaphyseal dysplasia - PS123000 - 2 Entries [7] Jun 1, 2018 — The x-rays of individuals with craniometaphyseal dysplasia show unusually shaped long bones, particularly long bones in the legs. [11] Summary. Autosomal dominant craniometaphyseal dysplasia (designated AD-CMD in this review) is characterized by progressive diffuse hyperostosis of cranial bones evident clinically as wide nasal bridge, paranasal bossing, widely spaced eyes with an increase in bizygomatic width, and prominent mandible. [13] Clinical characteristics: Autosomal dominant craniometaphyseal dysplasia (designated AD-CMD in this review) is characterized by progressive diffuse hyperostosis of cranial bones evident clinically as wide nasal bridge, paranasal bossing, widely spaced eyes with an increase in bizygomatic width, and prominent mandible.

Current Medical Management for Autosomal Dominant Craniometaphyseal Dysplasia

While there is no specific treatment available to cure autosomal dominant craniometaphyseal dysplasia (CMD), medical management can help alleviate symptoms and improve quality of life. According to recent research [7], symptomatic measures have been the primary approach in managing CMD.

• Surgical interventions: Invasive decompressive surgeries may be performed to relieve pressure on obstructed cranial foramina, which can help manage symptoms such as hearing loss and vision problems [6].
• Regular assessments: Patients with CMD require regular neurologic, ophthalmologic, and hearing assessment due to the progressive nature of bone thickening in the skull [6].

It's essential to note that medical management is focused on managing symptoms rather than treating the underlying condition. Research into understanding the molecular mechanisms behind CMD continues, which may lead to more targeted therapeutic approaches in the future.

References: [6] Sheppard WM (2003) - Patients with CMD require regular neurologic, ophthalmologic, and hearing assessment as the bone thickening is progressive. [7] Morelle G (2024) - To date, medical management had been limited to symptomatic measures—including invasive decompressive surgeries of obstructed cranial foramina.

Autosomal dominant craniometaphyseal dysplasia (AD-CMD) can be challenging to diagnose due to its rarity and overlapping symptoms with other conditions. However, several key factors can help differentiate it from other disorders.

Key Diagnostic Features of AD-CMD:

• Progressive diffuse hyperostosis: This is a hallmark feature of AD-CMD, characterized by the thickening of bones in the skull (cranium) and abnormalities in the metaphyses of long bones [1].
• Autosomal dominant inheritance: AD-CMD follows an autosomal dominant pattern of inheritance, meaning that a single copy of the mutated ANKH gene is sufficient to cause the condition [4].
• Radiographic findings: Radiographs typically show diffuse hyperostosis of the cranial base, cranial vault, facial bones, and mandible, as well as metaphyseal widening of long bones [8].

Differential Diagnosis:

When considering a diagnosis of AD-CMD, it is essential to rule out other conditions that may present with similar symptoms. Some of these differential diagnoses include:

• Fibrous dysplasia: This condition can also cause thickening of bones and abnormalities in the metaphyses of long bones [6].
• Osteopetrosis: A rare genetic disorder characterized by increased bone density, which can lead to cranial and facial deformities [3].
• Craniodiaphyseal dysplasia: A rare condition that affects the development of bones in the skull and face, leading to abnormalities in the shape and structure of these bones [7].

Diagnostic Approach:

A comprehensive diagnostic approach for AD-CMD involves a combination of clinical evaluation, radiographic imaging, and genetic testing. The diagnosis is typically made based on a combination of the following:

• Clinical presentation: A thorough medical history and physical examination can help identify symptoms such as progressive diffuse hyperostosis, facial deformities, and abnormalities in the metaphyses of long bones.
• Radiographic findings: Radiographs are essential for confirming the presence of diffuse hyperostosis and metaphyseal widening, which are characteristic features of AD-CMD.
• Genetic testing: Genetic analysis can confirm the presence of mutations in the ANKH gene, which is responsible for AD-CMD.

In conclusion, differential diagnosis of autosomal dominant craniometaphyseal dysplasia requires a comprehensive approach that takes into account clinical presentation, radiographic findings, and genetic testing. By considering these factors, healthcare professionals can accurately diagnose this rare condition and provide appropriate management and care for affected individuals.

References:

[1] Aug 27, 2007 — Autosomal dominant craniometaphyseal dysplasia (designated AD-CMD in this review) is characterized by progressive diffuse hyperostosis of ...

[4] Craniometaphyseal dysplasia is a very rare disorder; its incidence is unknown. Causes. Mutations in the ANKH gene cause autosomal dominant craniometaphyseal ...

[8] by E Reichenberger · 2020 · Cited by 8 — Diagnosis is based on clinical and radiographic findings that include diffuse hyperostosis of the cranial base, cranial vault, facial bones, and mandible as ...

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