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

Cleidocranial dysplasia


Other Names:
CLCD; Cleidocranial dysostosis; Dysplasia cleidocranial; CLCD; Cleidocranial dysostosis; Dysplasia cleidocranial; Marie-Sainton disease See More
Categories:
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

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 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
Respiratory distress
Breathing difficulties
Difficulty breathing
[ more ] 		0002098
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
Showing of 85 |
Last updated: 7/1/2020
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
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
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.
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

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

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 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

  • 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)
     

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

Social Networking Websites

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.

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.

  1. Mendoza-Londono R & Lee B. Cleidocranial dysplasia. GeneReviews. 2013; http://www.ncbi.nlm.nih.gov/books/NBK1513/.
  2. Cleidocranial dysplasia. Genetics Home Reference. January 2008; http://ghr.nlm.nih.gov/condition=cleidocranialdysplasia.