Última actualización:
June 28, 2019
Años publicados: 1989, 1997, 2005, 2019
NORD gratefully acknowledges Rachel Logan, NORD Editorial Intern from the Emory University Genetic Counseling Training Program and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, for assistance in the preparation of this report.
Summary
Craniometaphyseal dysplasia (CMD) is a rare disorder that involves the way the bones in the head, arms, and legs grow. The skull is made up of about 20 bones that grow and get larger as people grow. For persons with CMD, the bones of the skull grow too much and push into each other. When these bones push against each other, the pressure causes the symptoms of CMD. The bones of the head can also be unusually hard (sclerosis). CMD can cause mild changes in the shape of the face and head. MCD can also cause more serious symptoms such as hearing loss and blindness. Because of this, it is important that individuals with CMD see medical professionals that are knowledgeable about CMD and can watch for these symptoms.
CMD also causes the long bones in the legs and arms to be shaped differently. Persons with CMD can have unique facial features. Intelligence and quality of life are usually normal. CMD is often first noticed within the first few weeks of life and the symptoms are life-long. CMD is genetic and can be seen in multiple family members.
CMD is often first noticed within the first few weeks of life. The early symptoms of CMD are difficulty eating and breathing.
Persons with CMD have unique facial features. These can include widely-spaced eyes (hypertelorism), wide portion of the nose between the eyes (wide nasal bridge), and large lower jaw (mandible). The increased pressure caused by facial bone growth can cause the eyes to stick out further (proptosis). The head can also be unusually long in shape (dolichocephaly).
Hardening and increased growth of the bone that holds the teeth can cause teeth to come in late or not at all.
CMD can cause the air passages in the nose to be small. This can make it difficult for mucus to pass through, causing swelling in the nose and sinuses. This swelling can cause difficulty breathing.
Persons with CMD can develop different-shaped long bones in the arms and legs. These bones can be broad in the middle or “club-shaped” (metaphyseal dysplasia). The different-shaped bones are best seen on an x-ray and may not be noticeable by looking at a person.
If the pressure on the face and head is not reduced, some of the more severe symptoms of CMD can develop. The inability to move the muscles of the face can be caused by pressure on the nerves that connect to these muscles (cranial nerves). Hearing loss or deafness can be caused by pressure on the nerves that connect to the ears (sensorineural hearing loss) or pressure on the inside of the ear (conductive hearing loss). Blindness can be caused by pressure on the nerves that connect to the eye. Not all persons with CMD will have these features and they can often be prevented with surgery.
Individuals with CMD who do not have major complications can have a normal lifespan and a good quality of life.
CMD is a genetic condition caused by changes (mutations) in the genes ANKH or GJA1. The function of ANKH is to move a chemical called pyrophosphate in the body. The function of GJA1 is to create a passage for chemicals in the body between cells.
CMD can follow an autosomal recessive or autosomal dominant pattern of inheritance.
Recessive genetic disorders occur when an individual inherits an abnormal gene from each parent. In the recessive form, individuals have two non-working copies of the GJA1 gene. If an individual receives one normal gene and one abnormal gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the abnormal gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. In dominant form, persons have one working copy of ANKH gene and one non-working copy of the ANKH gene. The abnormal gene can be inherited from either parent or can be the result of a changed (mutated) gene in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
The dominant form of CMD is more common and tends to be milder than the recessive form. Persons with the recessive form can have a reduced life expectancy due to complications of pressure on the brain and spine.
CMD is a very rare disorder. Males and females are affected equally. Little is known about how many people have CMD.
A diagnosis of CMD can be made by an examination by a doctor familiar with craniofacial disorders. X-rays or other imaging are often required to diagnose and treat CMD. Genetic testing can also help diagnose CMD.
Treatment
The care team of individuals with CMD can include
– clinical genetics (care for genetic disorders)
– otolaryngology (care for the ears, nose, and throat)
– ophthalmology (care for the eye)
– neurology (care for the brain and nerves)
– endocrinology (care for growth of the bones)
– dentistry (care for the teeth)
– audiology (care for hearing)
There is no single treatment for CMD. Individual symptoms of CMD are treated as they arise.
Early surgical treatment to relieve pressure in the head and change the shape of the face bones may help reduce some of the complications of CMD.
Genetic counseling to determine the genetic cause and risk for other relatives may be helpful for persons with CMD and their families.
UConn Craniometaphyseal Dysplasia Research Study
https://health.uconn.edu/reichenberger-lab/craniometaphyseal-dysplasia-study/
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Martin K, Nathwani S, Bunyan R. Craniometaphyseal Dysplasia: A review and novel oral manifestation. J Oral Biol Craniofac Res. 2017;7(2):134-136.
Hu Y, Chen IP, de Almeida S, et al. A novel autosomal recessive GJA1 missense mutation linked to Craniometaphyseal dysplasia. PLoS One. 2013;8(8):e73576.
Kim SR, Han YS. Craniometaphyseal dysplasia. Arch Plast Surg. 2013;40(2):157-159.
INTERNET
O’Niell MJF and McKusick VA. Craniometaphyseal Dysplasia, Autosomal Dominant; CMDD. OMIM. https://www.omim.org/entry/123000. November 12, 2012. Accessed March 4, 2019.
O’Niell MJF and McKusick VA. Craniometaphyseal Dysplasia, Autosomal Recessive; CMDR. OMIM. https://www.omim.org/entry/218400. July 5, 2016. Accessed March 4, 2019.
Reichenberger E, Chen IP. Craniometaphyseal Dysplasia, Autosomal Dominant. 2007 Aug 27 [Updated 2015 Jan 15]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1461/
Accessed March 4, 2019.
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Aprende más https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
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