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

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	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormality of dental enamel	Abnormal tooth enamel Enamel abnormalities Enamel abnormality [ more ]	0000682
Carious teeth	Dental cavities Tooth cavities Tooth decay [ more ]	0000670
Down-sloping shoulders	Rounded shoulders Rounded, sloping shoulders Sloping shoulders [ more ]	0200021
Frontal bossing		0002007
High, narrow palate	Narrow, high-arched roof of mouth Narrow, highly arched roof of mouth [ more ]	0002705
Hypertelorism	Wide-set eyes Widely spaced eyes [ more ]	0000316
Hypoplasia of the zygomatic bone	Cheekbone underdevelopment Decreased size of cheekbone Underdevelopment of cheekbone [ more ]	0010669
Hypoplastic inferior ilia		0008821
Increased number of teeth	Extra teeth Increased tooth count Supplemental teeth [ more ]	0011069
Large fontanelles	Wide fontanelles	0000239
Micrognathia	Little lower jaw Small jaw Small lower jaw [ more ]	0000347
Narrow chest	Low chest circumference Narrow shoulders [ more ]	0000774
Recurrent respiratory infections	Frequent respiratory infections Multiple respiratory infections respiratory infections, recurrent Susceptibility to respiratory infections [ more ]	0002205
Short clavicles	Short collarbone	0000894
Short stature	Decreased body height Small stature [ more ]	0004322
Skeletal dysplasia		0002652
Sloping forehead	Inclined forehead Receding forehead [ more ]	0000340
Wormian bones	Extra bones within cranial sutures	0002645
30%-79% of people have these symptoms
Abnormal sacrum morphology		0005107
Abnormality of the metacarpal bones	Abnormality of the long bone of hand	0001163
Abnormality of the ribs	Rib abnormalities	0000772
Brachydactyly	Short fingers or toes	0001156
Chronic otitis media	Chronic infections of the middle ear	0000389
Decreased skull ossification	Decreased bone formation of skull	0004331
Delayed eruption of teeth	Delayed eruption Delayed teeth eruption Delayed tooth eruption Eruption, delayed Late eruption of teeth Late tooth eruption [ more ]	0000684
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
Dimple chin	Chin butt Chin dent Chin dimple Chin skin dimple Indentation of chin [ more ]	0010751
Hearing impairment	Deafness Hearing defect [ more ]	0000365
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
Midface retrusion	Decreased size of midface Midface deficiency Underdevelopment of midface [ more ]	0011800
Open bite	Absence of overlap of upper and lower teeth Open bite between upper and lower teeth [ more ]	0010807
Osteoporosis		0000939
Short face	Decreased height of face Decreased length of face Vertical shortening of face [ more ]	0011219
Sinusitis	Sinus inflammation	0000246
Spina bifida occulta		0003298
5%-29% of people have these symptoms
Abnormal thumb morphology	Abnormality of the thumb Abnormality of the thumbs Thumb deformity [ more ]	0001172
Abnormality of epiphysis morphology	Abnormal shape of end part of bone	0005930
Brachycephaly	Short and broad skull	0000248
Broad forehead	Increased width of the forehead Wide forehead [ more ]	0000337
Cleft palate	Cleft roof of mouth	0000175
Clinodactyly of the 5th finger	Permanent curving of the pinkie finger	0004209
Coxa vara		0002812
Dystrophic fingernails	Poor fingernail formation	0008391
Dystrophic toenail	Poor toenail formation	0001810
Genu valgum	Knock knees	0002857
Glossoptosis	Retraction of the tongue	0000162
Hypoplastic scapulae	Small shoulder blade	0000882
Macrocephaly	Increased size of skull Large head Large head circumference [ more ]	0000256
Recurrent fractures	Increased fracture rate Increased fractures Multiple fractures Multiple spontaneous fractures Varying degree of multiple fractures [ more ]	0002757
Scoliosis	Abnormal curving of the spine	0002650
Sleep apnea	Pauses in breathing while sleeping	0010535
Tapered finger	Tapered fingertips Tapering fingers [ more ]	0001182
Percent of people who have these symptoms is not available through HPO
Abnormal facility in opposing the shoulders		0005259
Absent frontal sinuses		0002688
Absent paranasal sinuses	Missing paranasal sinuses	0002689
Aplastic clavicle	Absent collarbone	0006660
Autosomal dominant inheritance		0000006
Cervical ribs		0000891
Cone-shaped epiphyses of the phalanges of the hand	Cone-shaped end part of finger bones	0010230
Delayed eruption of permanent teeth	Delayed eruption of adult teeth	0000696
Delayed eruption of primary teeth	Delayed eruption of baby teeth Delayed eruption of milk teeth Late eruption of baby teeth Late eruption of milk teeth [ more ]	0000680
Delayed pubic bone ossification		0008788
Hypoplasia of dental enamel	Underdeveloped teeth enamel	0006297
Hypoplastic frontal sinuses		0002738
Hypoplastic iliac wing		0002866
Increased bone mineral density	Increased bone density	0011001
Increased susceptibility to fractures	Abnormal susceptibility to fractures Bone fragility Frequent broken bones Increased bone fragility Increased tendency to fractures [ more ]	0002659
Kyphosis	Hunched back Round back [ more ]	0002808
Large foramen magnum	Big foramen magnum	0002700
Long second metacarpal	Long 2nd long bone of hand	0006040
Malar flattening	Zygomatic flattening	0000272
Moderately short stature	Moderate short stature	0008848
Neonatal respiratory distress	Infantile respiratory distress Newborn respiratory distress Respiratory distress, neonatal [ more ]	0002643
Parietal bossing		0000242
Persistent open anterior fontanelle		0004474
Short femoral neck	Short neck of thighbone	0100864
Short middle phalanx of the 2nd finger	Short middle bone of index finger	0009577
Short middle phalanx of the 5th finger	Short middle bone of the little finger Short middle bone of the pinkie finger Short middle bone of the pinky finger [ more ]	0004220
Short ribs		0000773
Spondylolisthesis	Displacement of one backbone compared to another Slipped backbone [ more ]	0003302
Spondylolysis		0003304
Syringomyelia	Fluid-filled cyst in spinal cord	0003396
Thickened calvaria	Increased thickness of skull cap Thickened skull cap [ more ]	0002684
Wide pubic symphysis		0003183

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 10/1/2019

Do you have updated information on this disease? We want to hear from you.

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

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

Find a Specialist Find a Specialist

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

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 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.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include mandibuloacral dysplasia, Crane-Heise syndrome, Yunis-Varon syndrome, pycnodysostosis, CDAGS syndrome, and hypophosphatasia. Visit the Orphanet disease page for more information.

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.

European Skeletal Dysplasia Network
Institute of Genetic Medicine
Newcastle University
International Centre for Life
Central Parkway
New Castle upon Tyne
Manchester M13 9PT
NE1 3BZ, United Kingdom
E-mail: info@esdn.org
Website: http://www.esdn.org/eug/Home

Patient Registry

A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Cleidocranial dysplasia. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

Registries for Cleidocranial dysplasia:
International Skeletal Dysplasia Registry (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: 1-800-535-3643
Telephone: +1-214-570-9099
Fax: +1-214-570-8811
E-mail: contactCCA@ccakids.com
Website: https://ccakids.org/
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/
Little People of America, Inc.
617 Broadway #518
Sonoma, CA 95476
Toll-free: 1-888-572-2001
Telephone: +1-714-368-3689
Fax: +1-707-721-1896
E-mail: info@lpaonline.org
Website: https://www.lpaonline.org/

Social Networking Websites

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

Do you know of an organization? We want to hear from you.

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

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.
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.

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