National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Craniometaphyseal dysplasia, autosomal dominant


Other Names:
CMDD; CMD; CMDJ; CMDD; CMD; CMDJ; Craniometaphyseal dysplasia Jackson type See More
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Autosomal dominant 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).[1][2] The overgrowth of bones in the head can lead to distinctive facial features and delayed tooth eruption, as well as compression of the cranial nerves.[1] If untreated, compression of the cranial nerves can be disabling.[2] The condition is caused by mutations in the ANKH gene. As the name suggests, it is inherited in an autosomal dominant manner.[1][2] Treatment may include surgery to reduce compression of cranial nerves and recontouring of the facial bones.[2]

 

Last updated: 4/11/2016

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.[1]

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.[1]

The symptoms seen in autosomal recessive craniometaphyseal dysplasia are typically more severe than those seen in the autosomal dominant form.[1]

Last updated: 4/11/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
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HPO ID
80%-99% of people have these symptoms
Abnormality of the metaphysis
Abnormality of the wide portion of a long bone
0000944
Craniofacial hyperostosis
Excessive bone growth of the skull and face
0004493
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root
[ more ] 		0005280
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Osteopetrosis
Harder, denser, fracture-prone bones
0011002
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge
[ more ] 		0000431
30%-79% of people have these symptoms
Skeletal dysplasia 0002652
Telecanthus
Corners of eye widely separated
0000506
5%-29% of people have these symptoms
Conductive hearing impairment
Conductive deafness
Conductive hearing loss
[ more ] 		0000405
Facial palsy
Bell's palsy
0010628
Sensorineural hearing impairment 0000407
Visual impairment
Impaired vision
Loss of eyesight
Poor vision
[ more ] 		0000505
Percent of people who have these symptoms is not available through HPO
Abnormality of pelvic girdle bone morphology
Abnormal shape of pelvic girdle bone
0002644
Abnormality of the nasopharynx 0001739
Abnormality of the vertebral column
Abnormal spine
Abnormal vertebral column
Abnormality of the spine
[ more ] 		0000925
Autosomal dominant inheritance 0000006
Bony paranasal bossing 0004407
Calvarial osteosclerosis 0005450
Club-shaped distal femur
Club-shaped outermost end of thighbone
0006384
Erlenmeyer flask deformity of the femurs
Erlenmeyer flask shaped thighbone
0004975
Macrocephaly
Increased size of skull
Large head
Large head circumference
[ more ] 		0000256
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw
[ more ] 		0000303
Metaphyseal widening
Broad wide portion of long bone
0003016
Misalignment of teeth
Abnormal dental position
Abnormal teeth spacing
Abnormality of alignment of teeth
Abnormality of teeth spacing
Crooked teeth
Malaligned teeth
Malposition of teeth
Malpositioned teeth
[ more ] 		0000692
Mixed hearing impairment
Hearing loss, mixed
Mixed hearing loss
[ more ] 		0000410
Nasal obstruction
Blockage of nose
Nasal blockage
Obstruction of nose
Stuffy nose
[ more ] 		0001742
Sclerosis of skull base
Dense bone of skull base
0002694
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Last updated: 7/1/2020

Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the ANKH gene.[1][2] The ANKH gene provides instructions for making a protein that is present in bone and transports a molecule called pyrophosphate out of cells. Pyrophosphate helps regulate bone formation by preventing mineralization, the process by which minerals such as calcium and phosphorus are deposited in developing bones. The ANKH protein may have other, unknown functions.[1]

Mutations in the ANKH gene that cause autosomal dominant craniometaphyseal dysplasia may decrease the ANKH protein's ability to transport pyrophosphate out of cells. Reduced levels of pyrophosphate can increase bone mineralization, contributing to the bone overgrowth seen in craniometaphyseal dysplasia. Why long bones are shaped differently and only the skull bones become thicker in people with this condition remains unclear.[1]

Last updated: 4/11/2016
Autosomal dominant craniometaphyseal dysplasia is inherited in an autosomal dominant pattern, which means one altered copy of the ANKH gene in each cell is sufficient to cause the disorder. Individuals with autosomal dominant craniometaphyseal dysplasia typically have one parent who also has the condition. Less often, cases result from new mutations in the gene and occur in people with no history of the disorder in their family.[1]
Last updated: 4/11/2016

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
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.[2]
Last updated: 4/11/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Craniometaphyseal dysplasia, autosomal dominant. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Craniometaphyseal dysplasia, autosomal dominant. Click on the link to view a sample search on this topic.

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  1. Craniometaphyseal dysplasia. Genetics Home Reference (GHR). February 2009; https://ghr.nlm.nih.gov/condition/craniometaphyseal-dysplasia.
  2. Reichenberger E, Chen IP. Craniometaphyseal Dysplasia, Autosomal Dominant. GeneReviews. January 15, 2015; http://www.ncbi.nlm.nih.gov/books/NBK1461/.