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Cleidocranial dysplasia

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Alternate names

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


Cleidocranial dysplasia (CCD) affects the development of the bones, skull, and teeth.

Mouth showing many over-retained deciduous teeth and some missing teeth.
Cleidocranial dysplasia teeth.jpg
Cleidocranial dysplasia face and shoulders.gif


Cleidocranial dysplasia occurs in approximately 1 per million individuals worldwide. It is likely underdiagnosed because many affected individuals have mild signs and symptoms.


  • Cleidocranial dysplasia is usually caused by mutations in the RUNX2 gene.
  • This gene provides instructions for making a protein that is involved in the development and maintenance of teeth, bones, and cartilage.
  • Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development.
  • Most cartilage is later converted to bone (a process called ossification), except for the cartilage that continues to cover and protect the ends of bones and is present in the nose, airways, and external ears.
  • The RUNX2 protein is a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. Researchers believe that the RUNX2 protein acts as a "master switch," regulating a number of other genes involved in the development of cells that build bones (osteoblasts) and in the development of teeth.

Gene mutations

  • The RUNX2 gene mutations that cause cleidocranial dysplasia reduce or eliminate the activity of the protein produced from one copy of the RUNX2 gene in each cell, decreasing the total amount of functional RUNX2 protein.
  • This shortage of functional RUNX2 protein interferes with the normal development of bones, cartilage, and teeth, resulting in the signs and symptoms of cleidocranial dysplasia.
  • In rare cases, individuals with a deletion of genetic material that includes RUNX2 and other nearby genes may experience additional features, such as developmental delay, resulting from the loss of these genes.
  • In about 30 percent of individuals with cleidocranial dysplasia, no mutation in the RUNX2 gene has been found. The cause of the condition in these individuals is unknown.


Autosomal dominant pattern, a 50/50 chance.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Some affected individuals inherit the mutation from one affected parent. Often the parent is mildly affected, and in some cases had not previously been recognized as having the disorder. Other cases result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.

Signs and 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:

  • 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.


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][1].

Clinical findings

  • Abnormally large, wide-open fontanelles at birth that may remain open throughout life. The wide-open metopic suture results in separation of the frontal bones by a metopic groove. The forehead is broad and flat; the cranium is brachycephalic.
  • Frontal and parietal bossing and mid-face retrusion
  • Narrow, sloping shoulders that can be opposed at the midline due to clavicular hypoplasia or aplasia
  • Abnormal dentition including delayed eruption of secondary dentition, failure to shed the primary teeth, variable numbers of supernumerary teeth along with dental crowding, and malocclusion
  • Hand abnormalities including brachydactyly, tapering fingers, and short, broad thumbs
  • Short stature (typically moderate)
  • Normal intellect in individuals with classic CCD spectrum disorder

Radiographic findings Cranium

  • Wide-open sutures, patent fontanelles, presence of wormian bones (small sutural bones)
  • Delayed ossification of the skull
  • Poor or absent pneumatization of the paranasal, frontal, and mastoid sinuses
  • Impacted, crowded teeth; supernumerary teeth


  • Cone-shaped thorax with narrow upper thoracic diameter
  • Typically bilateral (but not necessarily symmetric) clavicular abnormalities ranging from complete absence to hypoplastic or discontinuous clavicles. The lateral portions are more affected than the medial aspects of the clavicles .
  • Hypoplastic scapulae
  • Pelvis
  • Delayed ossification of the pubic bone with wide pubic symphysis
  • Hypoplasia of the iliac wings
  • Widening of the sacroiliac joints
  • Elongated femoral head with short femoral neck and elongated epiphyses ("chef-hat" appearance)
  • Coxa vara


  • Pseudoepiphyses of the metacarpal and metatarsal bones, which may result in a characteristic lengthening of the second metacarpal
  • Hypoplastic distal phalanges
  • Deformed and short middle phalanges of the third, fourth, and fifth digits with cone-shaped epiphyses


  • If the cranial vault defect is significant, the head needs protection from blunt trauma; helmets may be used for high-risk activities. [2][2].
  • Surgical cosmesis for depressed forehead or lengthening of hypoplastic clavicles can be considered.
  • If bone density is below normal, treatment with calcium and vitamin D supplementation is considered.
  • Dental procedures to address retention of deciduous dentition, presence of supernumerary teeth, and non-eruption of the permanent dentition.
  • Such procedures may include prosthetic replacements, removal of the supernumerary teeth followed by surgical repositioning of the permanent teeth, and a combination of surgical and orthodontic measures for actively erupting and aligning the impacted permanent teeth.
  • Speech therapy may be required during periods of dental treatment.
  • Aggressive treatment of sinus and middle ear infections; consideration of tympanostomy tubes for recurrent middle ear infections.


  1. Machol K, Mendoza-Londono R, Lee B. Cleidocranial Dysplasia Spectrum Disorder. 2006 Jan 3 [Updated 2017 Nov 16]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from:
  2. Machol K, Mendoza-Londono R, Lee B. Cleidocranial Dysplasia Spectrum Disorder. 2006 Jan 3 [Updated 2017 Nov 16]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from:

NIH genetic and rare disease info

Cleidocranial dysplasia is a rare disease.


WikiMD Resources - Cleidocranial dysplasia

Latest research (Pubmed)


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