Cleidocranial dysplasia

Title

Other Names:

CLCD; Cleidocranial dysostosis; Dysplasia cleidocranial; CLCD; Cleidocranial dysostosis; Dysplasia cleidocranial; Marie-Sainton disease See More

Categories:

Congenital and Genetic Diseases; Mouth Diseases; Musculoskeletal Diseases

Summary Summary

Cleidocranial dysplasia (CCD) is a condition that primarily affects the development of the bones and teeth. Characteristic features include underdeveloped or absent collarbones (clavicles); dental abnormalities; and delayed closing of the spaces between the skull bones (fontanels). Other features may include decreased bone density (osteopenia), osteoporosis, hearing loss, bone abnormalities of the hands, and recurrent sinus and ear infections. CCD is caused by changes (mutations) in the RUNX2 gene and inheritance is autosomal dominant. It may be inherited from an affected parent or occur due to a new mutation in the RUNX2 gene. Management may include dental procedures, treatment of sinus and ear infections, use of helmets for high-risk activities, and/or surgery for skeletal problems.^[1]^[2]

Last updated: 4/7/2016

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormality of dental enamel	Very frequent (present in 80%-99% of cases)
Carious teeth	Very frequent (present in 80%-99% of cases)
Down-sloping shoulders	Very frequent (present in 80%-99% of cases)
Frontal bossing	Very frequent (present in 80%-99% of cases)
High, narrow palate	Very frequent (present in 80%-99% of cases)
Hypertelorism	Very frequent (present in 80%-99% of cases)
Hypoplasia of the zygomatic bone	Very frequent (present in 80%-99% of cases)
Hypoplastic inferior ilia	Very frequent (present in 80%-99% of cases)
Increased number of teeth	Very frequent (present in 80%-99% of cases)
Large fontanelles	Very frequent (present in 80%-99% of cases)
Micrognathia	Very frequent (present in 80%-99% of cases)
Narrow chest	Very frequent (present in 80%-99% of cases)
Recurrent respiratory infections	Very frequent (present in 80%-99% of cases)
Short clavicles	Very frequent (present in 80%-99% of cases)
Skeletal dysplasia	Very frequent (present in 80%-99% of cases)
Sloping forehead	Very frequent (present in 80%-99% of cases)
Wormian bones	Very frequent (present in 80%-99% of cases)
Abnormality of the metacarpal bones	Frequent (present in 30%-79% of cases)
Abnormality of the ribs	Frequent (present in 30%-79% of cases)
Abnormality of the sacrum	Frequent (present in 30%-79% of cases)
Brachydactyly	Frequent (present in 30%-79% of cases)
Chronic otitis media	Frequent (present in 30%-79% of cases)
Decreased skull ossification	Frequent (present in 30%-79% of cases)
Delayed eruption of teeth	Frequent (present in 30%-79% of cases)
Dimple chin	Frequent (present in 30%-79% of cases)
Hearing impairment	Frequent (present in 30%-79% of cases)
Midface retrusion	Frequent (present in 30%-79% of cases)
Open bite	Frequent (present in 30%-79% of cases)
Osteoporosis	Frequent (present in 30%-79% of cases)
Short face	Frequent (present in 30%-79% of cases)
Sinusitis	Frequent (present in 30%-79% of cases)
Spina bifida occulta	Frequent (present in 30%-79% of cases)
Abnormality of epiphysis morphology	Occasional (present in 5%-29% of cases)
Abnormality of the thumb	Occasional (present in 5%-29% of cases)
Brachycephaly	Occasional (present in 5%-29% of cases)
Broad forehead	Occasional (present in 5%-29% of cases)
Clinodactyly of the 5th finger	Occasional (present in 5%-29% of cases)
Coxa vara	Occasional (present in 5%-29% of cases)
Dystrophic fingernails	Occasional (present in 5%-29% of cases)
Dystrophic toenail	Occasional (present in 5%-29% of cases)
Genu valgum	Occasional (present in 5%-29% of cases)
Glossoptosis	Occasional (present in 5%-29% of cases)
Hypoplastic scapulae	Occasional (present in 5%-29% of cases)
Macrocephaly	Occasional (present in 5%-29% of cases)
Recurrent fractures	Occasional (present in 5%-29% of cases)
Scoliosis	Occasional (present in 5%-29% of cases)
Sleep apnea	Occasional (present in 5%-29% of cases)
Tapered finger	Occasional (present in 5%-29% of cases)
Abnormal facility in opposing the shoulders	-
Absent frontal sinuses	-
Absent paranasal sinuses	-
Aplastic clavicles	-
Autosomal dominant inheritance	-
Cervical ribs	-
Cone-shaped epiphyses of the phalanges of the hand	-
Delayed eruption of permanent teeth	-
Delayed eruption of primary teeth	-
Delayed pubic bone ossification	-
High palate	-
Hypoplasia of dental enamel	-
Hypoplastic frontal sinuses	-
Hypoplastic iliac wing	-
Increased bone mineral density	-
Increased susceptibility to fractures	-
Kyphosis	-
Large foramen magnum	-
Long second metacarpal	-
Malar flattening	-
Moderately short stature	-
Narrow palate	-
Neonatal respiratory distress	-
Parietal bossing	-
Persistent open anterior fontanelle	-
Short femoral neck	-
Short middle phalanx of the 2nd finger	-
Short middle phalanx of the 5th finger	-
Short ribs	-
Spondylolisthesis	-
Spondylolysis	-
Syringomyelia	-
Wide pubic symphysis	-

Last updated: 9/1/2017

Cause Cause

Cleidocranial dysplasia (CCD) is typically caused by changes (mutations) in the RUNX2 gene. This gene gives the body instructions to make a protein used in the development and maintenance of bone and cartilage.^[2]

Researchers believe that the RUNX2 protein acts like a "switch" that regulates other genes involved in the development of cells that build bones (osteoblasts). Mutations in the RUNX2 gene result in a shortage of normal protein, which in turn affects normal bone and cartilage development.^[2]

In some cases, no mutation or genetic abnormalities affecting the RUNX2 gene are found. The cause of the condition in these cases is currently unknown.^[1]

Last updated: 4/7/2016

Inheritance Inheritance

Cleidocranial dysplasia is inherited in an autosomal dominant manner.^[2]^[1] This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition.

In some cases, an affected person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation.

When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.

There is nothing a parent can do before, during, or after a pregnancy to cause cleidocranial dysplasia in a child.

Last updated: 4/7/2016

Diagnosis Diagnosis

A person with features of cleidocranial dysplasia (CCD) or any other skeletal dysplasia should be referred to an orthopedist. If the doctor suspects a diagnosis of CCD, a skeletal survey (series of X-rays) should be ordered. The skeletal survey should include specific X-rays of the skull and thorax (chest); pelvis; lumbar spine (lower back); and long bones, hands, and feet.

Genetic testing of the RUNX2 gene, the only gene known to cause CCD, can be considered to confirm the diagnosis. This is particularly if the signs and symptoms found in the physical exam and X-rays do not meet the diagnostic criteria.

People with uncommon features of CCD and developmental delay may have another type of genetic testing called chromosomal microarray (CMA) to look for small missing pieces of chromosomes (microdeletions) or small extra pieces (microduplications) that involve the RUNX2 gene. If CMA does not confirm the diagnosis and CCD is still strongly suspected, a karyotype (organized chromosome picture) may still be considered to look for rearrangements of genetic material.

During a pregnancy, a fetus at risk can be tested for CCD if the genetic cause of the condition has already been identified in a family member. This is called prenatal diagnosis. This can be done by testing the DNA of fetal cells obtained by amniocentesis (in the 2nd trimester) or chorionic villus sampling (in the 1st trimester).

CCD may also be diagnosed in a pregnancy by an ultrasound of the fetus of an affected parent. CCD may be apparent on ultrasound as early as 14 weeks' gestation. The most common features seen on ultrasound are abnormal collarbones (clavicles), which are either very short, partially absent, or totally absent.^[1]

A number of other conditions share some characteristics with CCD. You can read about these conditions and their features on the GeneReviews website by clicking here.

Last updated: 7/26/2016

People with questions about a possible diagnosis of cleidocranial dysplasia (CCD) and are interested in genetic testing should first meet with an orthopedist and/or a professional who specializes in genetics (medical geneticist or genetic counselor). These specialists, either alone or working together, can:

perform a thorough physical exam,
evaluate the medical and family history,
order laboratory or imaging studies,
address questions and concerns,
facilitate genetic testing if appropriate and desired, and
assess recurrence risks to other family members.

A number of other conditions share some characteristics with CCD, and a specialist can help determine whether genetic testing for CCD, or possibly a different skeletal dysplasia, would be most informative.

The Genetic Testing Registry (GTR) provides information about the genetic tests for CCD and the laboratories that offer testing. However, 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.

To find a medical professional who specializes in genetics in your area, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Last updated: 7/27/2016

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.
Orphanet lists international laboratories offering diagnostic testing for this condition.

Treatment Treatment

There is no specific treatment for cleidocranial dysplasia (CCD), and management is based on each person's symptoms. Most people with CCD need dental care due to various dental abnormalities. If bone density is below normal, supplements of calcium and vitamin D may be needed, and preventive treatment for osteoporosis may be started at a young age. Those with frequent ear infections may need ear tubes. Severe defects of the cranial vault (space in the skull occupied by the brain) should be protected by wearing helmets during high-risk activities. Surgery may be needed to correct any of various skeletal (bone) abnormalities.^[1]

Last updated: 4/7/2016

Management Guidelines

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.

Do you have updated information on this condition? Let us know.

Research Research

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 U.S. National Institutes of Health, through the National Library of Medicine, developed ClinicalTrials.gov to provide patients, family members, and members of the public with current information on clinical research studies. There is a study titled Evaluation and Treatment of Skeletal Diseases which may be of interest to you.
Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition.

Patient Registry

International Skeletal Dysplasia Registry
UCLA-OHRC
Attn: Alisa Zargaryan
615 Charles E. Young Drive
South, Room 410
Los Angeles, CA 90095-7358
Telephone: 310-825-8998
E-mail: AZargaryan@mednet.ucla.edu
Web site: http://ortho.ucla.edu/isdr

Greenberg Center for Skeletal Dysplasias
Johns Hopkins University
Institute of Genetic Medicine
600 North Wolfe Street
Blalock 1008
Baltimore, MD 21287
Telephone: 410-614-0977
E-mail: deedee@jhmi.edu
Website: http://www.hopkinsmedicine.org/institute-genetic-medicine/patient-care/genetics-clinic/about/greenberg-center-skeletal-dysplasia/

Organizations Organizations

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

Ameriface
PO Box 751112
Las Vegas, NV 89136
Toll-free: 888-486-1209
Telephone: 702-769-9264
E-mail: info@ameriface.org
Website: http://www.ameriface.org
Children's Craniofacial Association
13140 Coit Road Suite 517
Dallas, TX 75240
Toll-free: 800-535-3643
Telephone: 214-570-9099
Fax: 214-570-8811
E-mail: contactCCA@ccakids.com
Website: http://www.ccakids.com/
European Skeletal Dysplasia Network
Wellcome Trust Centre for Cell-Matrix Research
Faculty of Life Sciences
University of Manchester
Michael Smith Building
Oxford Road
Manchester M13 9PT
United Kingdom
Telephone: 0161 276 3202
Fax: 0161 276 4058
E-mail: info@esdn.org
Website: http://www.esdn.org/eug/Home
FACES: The National Craniofacial Association
PO Box 11082
Chattanooga, TN 37401
Toll-free: 800-332-2373
Telephone: 423-266-1632
E-mail: faces@faces-cranio.org
Website: http://www.faces-cranio.org/

Social Networking Websites

Visit the following Facebook groups or pages related to Cleidocranial dysplasia:
Cleidocranial dysplasia (CCD) Family Support Group
Parents with children with Cleidocranial Dysplasia

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

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 Cleidocranial dysplasia. This website is maintained by the National Library of Medicine.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
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

MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
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 Cleidocranial dysplasia. Click on the link to view a sample search on this topic.

News & Events News & Events

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017
Young Investigator Initiative Career Development and Grant Mentoring Program
June 21, 2016

NCATS Co-Sponsored Conferences

18th International RUNX Workshop Sunday, August 14, 2011 - Wednesday, August 17, 2011
Location: Eleanor Roosevelt College, University of California, San Diego, La Jolla, CA
Description: Based on the long-standing interactive and inter-disciplinary traditions of the 17 previous RUNX workshops, the organizers anticipate that the 18th International RUNX Workshop will offer excellent opportunities for the cross-pollination of ideas and the development of new collaborations in this rapidly expanding field.

Contact: Dr. Yvonne Douglas-Tabor(301) 496-1785

Co-funding Institute(s): National Cancer Institute, Office of Rare Diseases Research
- Agenda ( - 139KB)

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

I am 60 years old, and have not been diagnosed with this. However I have lived in the dark with many of the symptoms. I live in constant pain, and numerous doctors over the years could not tell me what is wrong with me. My question is how and where can I get genetic testing? It's too late for any help for me, however my daughter is about to have her first child, and I am worried my granddaughter may have the RUN2 gene. See answer
My 25-year-old son has cleidocranial dysplasia. His condition is mild, but he has endured treatments for hearing loss and orthodontic conditions. We were told at the time of his diagnosis that his children would have a 50/50 chance of inheriting this condition. Is that still the case? Are there any treatments or therapies to prevent him from passing this on?
See answer
My daughter and I have cleidocranial dysplasia. Can you help us with information on treatment of our disease?
See answer