Rare Pulmonology News

Disease Profile

Cleidocranial dysplasia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

1-9 / 1 000 000

US Estimated

Europe Estimated

Age of onset

Neonatal

ICD-10

Q74.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

CLCD; Cleidocranial dysostosis; Dysplasia cleidocranial;

Categories

Congenital and Genetic Diseases; Mouth Diseases; Musculoskeletal Diseases

Summary

Cleidocranial dysplasia (CCD) affects the development of the bones, skull, and teeth. Signs and symptoms include underdeveloped or absent collarbones (clavicles), dental abnormalities, and delayed closing of the spaces between the skull bones (fontanels). Other symptoms may include decreased bone density (osteopenia), hearing loss, bone abnormalities of the hands, and recurrent sinus and ear infections. People with CCD may develop curvature of the spine (scoliosis), osteoporosis, and may be shorter than average. CCD occurs due to a RUNX2 gene that is not working correctly and is inherited in an autosomal dominant pattern. Diagnosis is based on the symptoms, clinical exam, imaging studies, and genetic testings. Treatment is focused on managing the symptoms, and may include dental procedures and surgery.[1][2][3][4][5]

Symptoms

The following list includes the most common signs and symptoms in people with cleidocranial dysplasia. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Signs and symptoms may include:[1][2][4]

  • Delayed closure of the skull bones (open fontanelles)
  • Underdevelopment of the collarbones (clavicles)
  • Bone abnormalities in the hands
  • Abnormal teeth
  • Decreased bone density (osteopenia, osteoporosis)

Additional symptoms may include curvature of the spine, delayed growth, and hearing loss. People with cleidocranial dysplasia typically have average intelligence.

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.

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
T

Cause

Cleidocranial dysplasia (CCD) occurs when the RUNX2 gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[1][3]

Diagnosis

Cleidocranial dysplasia (CCD) is diagnosed based on the symptoms, a clinical exam, imaging studies and the results of genetic testing. Imaging studies may include a skeletal survey (series of X-rays of the bones of the skeleton) and dental x-rays.[1][4]

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 of cleidocranial dysplasia (CCD) is focused on managing the symptoms. Most people with CCD need dental and orthodontic care due to various dental abnormalities. Surgery may be needed to correct more severe skeletal (bone) abnormalities.[1][5]

    Specialists involved in the care of someone with cleidocranial dysplasia may include: 

    • Craniofacial surgeon
    • Dentist
    • Orthodontist
    • Endocrinologist
    • Otolaryngologist (ENT doctor)
    • Orthopedist

    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

      Social Networking Websites

        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

        • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
        • Genetics Home Reference (GHR) contains information on Cleidocranial dysplasia. 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.
          • 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.

            References

            1. Machol K, Mendoza-Londono R, Lee B. Cleidocranial Dysplasia Spectrum Disorder. GeneReviews. Updated Nov. 16, 2017; https://www.ncbi.nlm.nih.gov/books/NBK1513.
            2. Cooper SC, Flaitz CM, Johnston DA, Lee B, Hecht JT. A natural history of cleidocranial dysplasia. Am J Med Genet. 2001; 104(1):1-6. https://pubmed.ncbi.nlm.nih.gov/1174602.
            3. Dinçsoy Bir F, Dinçkan N, Güven Y, et al. Cleidocranial dysplasia: Clinical, endocrinologic and molecular findings in 15 patients from 11 families. Eur J Med Genet. 2017; 60(3):163-168. https://pubmed.ncbi.nlm.nih.gov/28027977.
            4. Farrow E, Nicot R, Wss A, Laborde A, Ferri J. Cleidocranial Dysplasia: A Review of Clinical, Radiological, Genetic Implications and a Guidelines Proposal. J Craniofac Surg. 2018; 29(2):382-389. https://pubmed.ncbi.nlm.nih.gov/29189406.
            5. Li J, Shen J, Xu J, Weng L, Pan J, Lin J. The Treatment Strategy of Cleidocranial Dysplasia: Combined Orthodontic and Orthognathic Treatment. J Craniofac Surg. 2019; 30(6):1767-1771. https://pubmed.ncbi.nlm.nih.gov/30950953.

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