Craniometaphyseal dysplasia, autosomal recessive type

Alternate names

CMDR

Definition

Autosomal recessive craniometaphyseal dysplasia is a genetic skeletal condition characterized by progressive thickening of bones in the skull (cranium) and abnormalities at the ends of long bones in the limbs (metaphyseal dysplasia).

Epidemiology

Craniometaphyseal dysplasia is a very rare disorder; its incidence is unknown.

Cause

• A mutation in the GJA1 gene causes some cases of autosomal recessive craniometaphyseal dysplasia.
• This gene provides instructions for making a protein called connexin 43, which is involved in the development of many tissues in the body, including bone.
• The protein may be involved in bone remodeling.
• It is unclear how a mutation in the GJA1 gene leads to the particular bone abnormalities of craniometaphyseal dysplasia.
• The genetic cause of many cases of autosomal recessive craniometaphyseal dysplasia is unknown. It is likely that other, unidentified genes are involved in this form of the disorder.

Inheritance

Autosomal recessive inheritance, a 25% chance

When caused by mutations in the GJA1 gene, craniometaphyseal dysplasia has an autosomal recessive inheritance pattern, which means both copies of the GJA1 gene in each cell are altered. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the disorder.

Signs and symptoms

• Bone overgrowth in the head causes many of the signs and symptoms of craniometaphyseal dysplasia.
• Affected individuals typically have distinctive facial features such as a wide nasal bridge, a prominent forehead, wide-set eyes (hypertelorism), and a prominent jaw. Excessive new bone formation (hyperostosis) in the jaw can delay teething (dentition) or result in absent teeth.
• Infants with this condition may have breathing or feeding problems caused by narrow nasal passages.
• In severe cases, abnormal bone growth can compress the nerves that emerge from the brain and extend to various areas of the head and neck (cranial nerves). Compression of the cranial nerves can lead to paralyzed facial muscles (facial nerve palsy), blindness, or deafness.
• The x-rays of individuals with craniometaphyseal dysplasia show unusually shaped long bones, particularly the large bones in the legs. The ends of these bones (metaphyses) are wider and appear less dense in people with this condition.
• The symptoms seen in autosomal recessive craniometaphyseal dysplasia are typically more severe than those seen in the autosomal dominant form.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Abnormality of the metaphysis(Abnormality of the wide portion of a long bone)
• Craniofacial hyperostosis(Excessive bone growth of the skull and face)
• Depressed nasal bridge(Depressed bridge of nose)
• [[Hypertelorism](Wide-set eyes)
• Osteopetrosis(Harder, denser, fracture-prone bones)
• Wide nasal bridge(Broad nasal bridge)

30%-79% of people have these symptoms

• Skeletal dysplasia
• Telecanthus(Corners of eye widely separated)

5%-29% of people have these symptoms

• Conductive hearing impairment(Conductive deafness)
• Facial palsy(Bell's palsy)
• Sensorineural hearing impairment
• Visual impairment(Impaired vision)

Diagnosis

• Craniometaphyseal dysplasia is diagnosed based on clinical and radiographic findings that include hyperostosis.
• Some things such as cranial base sclerosis and nasal sinuses obstruction can be seen during the beginning of the child's life.
• In radiographic findings the most common thing that will be found is the narrowing of foramen magnum and the widening of long bones.

Treatment

• Treatment consists primarily of surgery to reduce compression of cranial nerves and the brain stem/spinal cord at the level of the foramen magnum.
• Severely overgrown facial bones can be contoured; however, surgical procedures can be technically difficult and bone regrowth is common.
• Individuals with craniometaphyseal dysplasia should have regular neurologic evaluations, hearing assessments, and ophthalmologic examinations.
• The frequency of these evaluations and assessments should be determined by the individual's history and severity of skeletal changes.

NIH genetic and rare disease info

• NIH info on Craniometaphyseal dysplasia, autosomal recessive type

Craniometaphyseal dysplasia, autosomal recessive type is a rare disease.

Craniometaphyseal dysplasia, autosomal recessive type Resources
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