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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.
Features include always present findings: Parietal bossing and Abnormal facility in opposing the shoulders; and very common findings: Short stature, Hypertelorism, Large fontanelles, and High, narrow palate and others. 93 total HPO annotations.
Organ System | Phenotype Count | Example Features |
|---|---|---|
Bones and joints | 13 | Wide sacroiliac joint, Increased susceptibility to fractures, Short femoral neck |
Head and neck | 7 | Cleft palate, High, narrow palate, Narrow palate |
Arms and legs | 7 | Short middle phalanx of the 2nd finger, Short middle phalanx of the 5th finger, Cone-shaped epiphyses of the phalanges of the hand |
Lungs and breathing | 4 | Respiratory distress, Neonatal respiratory distress, Recurrent respiratory infections |
Ears | 3 | Hearing loss (hearing impairment), Chronic otitis media, Hearing abnormality |
Growth and development | 2 | Moderately short stature, Short stature |
Brain and nerves | 1 | Depressed nasal bridge |
Pregnancy and birth | 1 | Neonatal respiratory distress |
Blood and immune system | 1 | Recurrent respiratory infections |
Cleidocranial dysplasia (CCD) spectrum disorder is a skeletal dysplasia representing a clinical continuum ranging from classic CCD (triad of delayed closure of the cranial sutures, hypoplastic or aplastic clavicles, and dental abnormalities), to mild CCD, to isolated dental anomalies without other skeletal features . Most individuals are diagnosed because they have classic features. CCD spectrum disorder affects most prominently those bones derived from intramembranous ossification, such as the cranium and the clavicles, although bones formed through endochondral ossification can also be affected.
Source: GeneReviews — "Cleidocranial Dysplasia Spectrum Disorder"
RUNX2 function has not been fully characterized.
Cleidocranial dysplasia 1 is associated with mutations in the RUNX2 gene on chromosome 6.
Some genotype-phenotype correlations have been established for the dental manifestations seen in CCD spectrum disorder. No clear correlation has been established between genotype and clavicular involvement .
Source: GeneReviews — "Cleidocranial Dysplasia Spectrum Disorder"
Pathogenic variants in RUNX2 have high penetrance. To date, there are no reports of incomplete penetrance.
Source: GeneReviews — "Cleidocranial Dysplasia Spectrum Disorder"
Cleidocranial dysplasia (CCD) spectrum disorder is a skeletal dysplasia that represents a continuum of clinical and radiographic findings ranging from classic CCD (triad of delayed closure of the cranial sutures, hypoplastic or aplastic clavicles, and dental abnormalities), to mild CCD, to isolated dental anomalies without other skeletal features. No formal clinical diagnostic criteria for CCD spectrum disorder have been established.
CCD spectrum disorder should be suspected in probands with the following clinical and radiographic findings.
Clinical findings
Source: GeneReviews — "Cleidocranial Dysplasia Spectrum Disorder"
Other conditions share some characteristics with cleidocranial dysplasia (CCD) spectrum disorder. The fact that similar skeletal elements are affected suggests that some of these conditions may result from mutation of genes (most notably CBFB) that affect the action of RUNX2 on its downstream targets (CBFB forms a heterodimer with RUNX2 to activate transcription of downstream targets). Table 2. Genes of Interest in the Differential Diagnosis of Cleidocranial Dysplasia Spectrum Disorder
Gene/ GeneticMechanism | Disorder | MOI | Craniofacial Dental Features | Skeletal Features | Other Features |
|---|---|---|---|---|---|
ALPL |
Genetic testing for RUNX2 is available. Testing is considered confirmatory for diagnosis.
Biomarker and diagnostic research for cleidocranial dysplasia 1 has been reported in the published literature.
No approved treatments are currently available for cleidocranial dysplasia 1. The disease remains an area of unmet medical need.
No clinical practice guidelines for cleidocranial dysplasia (CCD) spectrum disorder have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with CCD spectrum disorder, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with Cleidocranial Dysplasia Spectrum Disorder
System/Concern | Evaluation | Comment |
|---|---|---|
Dental | Dental eval by dentist familiar w/CCD spectrum disorder its mgmt | — |
Hearing | Audiologic eval | — |
Genetic counseling | By genetics professionals1 | To inform affected persons their families re nature, MOI, implications of CCD spectrum disorder to facilitate medical personal decision making CCD = cleidocranial dysplasia; DXA = dual-energy x-ray absorptiometry; MOI = mode of inheritance 1. |
Treatment of Manifestations in Individuals with Cleidocranial Dysplasia Spectrum Disorder Manifestation/Concern | Treatment | Considerations/Other |
Hypoplastic clavicles | Affected persons may consider lengthening hypoplastic clavicles for cosmetic reasons.1 |
Source: GeneReviews — "Cleidocranial Dysplasia Spectrum Disorder"
To avoid head trauma, helmets and protective devices should be worn when participating in high-risk sports and activities.
Source: GeneReviews — "Cleidocranial Dysplasia Spectrum Disorder"
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
Source: GeneReviews — "Cleidocranial Dysplasia Spectrum Disorder"
1 trial found
To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 5. Recommended Surveillance for Individuals with Cleidocranial Dysplasia Spectrum Disorder
System/Concern | Evaluation | Frequency |
|---|---|---|
Skeletal | Orthopedic assessment for skeletal manifestations (pes planus, genu valgum, scoliosis, recurrent shoulder or elbow dislocations) | At each visit throughout childhood DXA scan to measure bone mineral density (to assess for osteoporosis) |
Dental | Dental eval by dentist familiar w/CCD spectrum disorder its mgmt | Every 6 mos or more frequently as recommended by dentist beginning at age 3 yrs ENT |
Development | Assessment of speech | At each visit during times of dental treatment in those w/recurrent ear infections /or hearing issues DXA = dual-energy x-ray absorptiometry |
Source: GeneReviews — "Cleidocranial Dysplasia Spectrum Disorder"
Phenotype severity distribution: 2 always present features, 19 very common features, 22 common features.
Estimated prevalence: 1-9 in 1,000,000 (Rare).
1 clinical trial registered. Interventions under study include other interventions. Research is primarily sponsored by academic and government institutions.
59 publications have been identified in PubMed for cleidocranial dysplasia 1. Research spans Case Report / Case Series (47%), Basic Science / Preclinical (34%), and Review / Meta-Analysis (10%).
Research Type | Count | % of Total |
|---|---|---|
Patient case studies | 28 | 47% |
Laboratory research | 20 | 34% |
Research summaries | 6 | 10% |
Other research | 1 | 2% |
Testing and diagnosis research | 1 | 2% |
Clinical study results | 1 | 2% |
Disease patterns and progression | 1 | 2% |
New treatment approaches | 1 | 2% |
Thangabalu R (2026). [PMID: 41887811](https://pubmed.ncbi.nlm.nih.gov/41887811/). *Am J Orthod Dentofacial Orthop*. [Other]
Cao Y (2026). [PMID: 41593433](https://pubmed.ncbi.nlm.nih.gov/41593433/). *Hong Kong medical journal = Xianggang yi xue za zhi*. [Case Report / Case Series]
Hoover-Fong J (2026). [PMID: 41504382](https://pubmed.ncbi.nlm.nih.gov/41504382/). *Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research*. [Case Report / Case Series]
Seengar D (2026). [PMID: 41496953](https://pubmed.ncbi.nlm.nih.gov/41496953/). *Annals of medicine and surgery (2012)*. [Clinical Trial Publication]
Hung CY (2026). [PMID: 41645457](https://pubmed.ncbi.nlm.nih.gov/41645457/). *Congenital anomalies*. [Basic Science / Preclinical]
Sobti R (2026). [PMID: 42138615](https://pubmed.ncbi.nlm.nih.gov/42138615/). *Cleft Palate Craniofac J*. [Case Report / Case Series]
Jiang Q (2026). [PMID: 42111267](https://pubmed.ncbi.nlm.nih.gov/42111267/). *Front Cell Dev Biol*. [Basic Science / Preclinical]
Bous R (2026). [PMID: 41201411](https://pubmed.ncbi.nlm.nih.gov/41201411/). *American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics*. [Case Report / Case Series]
Kashiki H (2026). [PMID: 42243079](https://pubmed.ncbi.nlm.nih.gov/42243079/). *Hum Genome Var*. [Basic Science / Preclinical]
Ogata S (2026). [PMID: 42001716](https://pubmed.ncbi.nlm.nih.gov/42001716/). *Biochem Biophys Res Commun*. [Basic Science / Preclinical]
Data assembled from 8 of 12 sources · Last updated Oct 3, 2026, 5:09 PM UTC
Online Mendelian Inheritance in Man
European rare disease database
Genetic and Rare Diseases Info Center
Common questions about cleidocranial dysplasia 1
ARAD2 |
Children w/infantile form may present w/very poorly mineralized cranium widened cranial sutures.; Premature deciduous tooth loss |
Generalized defect of mineralization w/delayed ossification of multiple skeletal elements; Children w/infantile form may present w/short ribs narrow thorax.; Clavicles least affected; Rachitic skeletal changes |
Very low alkaline phosphatase activity in serum tissues; Nephrocalcinosis |
Hypercalcemia CBFB(intragenic pathogenic variants) | CBFB-related CCD (OMIM 620099) | AD | Delayed closure of fontanelle; Delayed/absent eruption of deciduous teeth; Supernumerary teeth | Hypoplastic or absent clavicles, clavicula bipartita; Metacarpal/metatarsal pseudoepiphyses; Delayed ossification of pubic carpal bones; Short distal phalanges | Normal stature |
DD (mild to moderate) CBFB(16q22.1 deletions involving CBFB) | Chromosome 16q22 deletion syndrome (OMIM 614541) | AD | Wide-open fontanelles | Short clavicles3; Short stature; Short distal phalanges; Delayed ossification of skull | Poor weight gain; DD; Congenital heart defect CTSK |
Pycnodysostosis | AR | Failure of closure of cranial sutures w/persistence of open fontanelles | Acro-osteolysis; Osteopetrosis; radio-opacity of all bones due to density of trabecular bone but not cortices; Short stature w/ bone fragility, short terminal phalanges | — | — |
FIG4 | Yunis Varon syndrome (OMIM 216340) | AR | Wide-open fontanelles sutures; Unusual mineralization of skull | Hypoplastic clavicles; Absence/hypoplasia of thumbs, halluces, distal phalanges; Gracile bones | Prenatal growth deficiency; Brain malformations LMNA |
ZMPSTE24 | Mandibuloacral dysplasia (OMIM PS248370) | AR | Delayed closure of cranial sutures; Micrognathia; Early tooth loss | Dysplastic clavicles; Acro-osteodysplasia of fingers toes w/delayed ossification of carpal bones; Progressively stiff joints; Short stature | Alopecia; scalp hair sparse by 3rd decade; Atrophic skin w/ subcutaneous fat |
Skin hyperpigmentation MSX2(intragenic pathogenic variants) | Parietal foramina w/CCD4 | AD | Enlarged parietal foramina; Broad forehead w/frontal bossing | — | — |
Not assoc w/dental abnormalities | Clavicular hypoplasia | MSX2(m... | — | — | — |
Source: GeneReviews — "Cleidocranial Dysplasia Spectrum Disorder"
Osteoporosis | Calcium vitamin D supplementation for those w/bone density below normal on DXA scan | — |
Dental manifestations | Early referral to dental clinic familiar w/CCD allows for timely planning of necessary procedures. | Generally, an aggressive approach to coordinate multiple oral surgeries for removal of primary dentition exposure of permanent dentition is recommended; watchful waiting for spontaneous eruption after initial delay is not effective. |
Speech issues | Speech therapy as needed during periods of dental treatment /or in those w/speech issues related to hearing impairment. | Sinus middle ear infections4 |
Short stature | No treatment recommended | Efficacy of GH therapy in CCD has not been proven.; Possible adverse effects of GH therapy on primary chondrodysplastic growth plate are theoretically possible, as RUNX2 is directly involved in chondrocyte differentiation growth plate maintenance. |
AI-curated news mentioning cleidocranial dysplasia 1
Updated Jun 4, 2026
A novel de novo splice-site variant in the RUNX2 gene has been identified as a cause of cleidocranial dysplasia. This discovery enhances the understanding of the genetic basis of this rare skeletal disorder.