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Cleidocranial dysplasia
This condition is characterised by abnormal development of bones, especially those in the skull and collarbones, and issues with tooth eruption. It is present from birth and can affect individuals of all ages and backgrounds.
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Overview
Cleidocranial dysplasia (CCD) is a congenital disorder impacting the development of bones and teeth throughout the body [PMID:33608757]. It is typically characterised by distinctive features affecting the skull, collarbones (clavicles), and dentition. The severity of these features can vary significantly between individuals. This condition is rare, affecting approximately 1 in 1,000,000 live births, and is present from birth, meaning affected individuals are born with the condition [PMID:33608757].
A hallmark feature of CCD is the partial or complete absence of the collarbones, which can give individuals increased mobility in their shoulders, allowing them to bring them closer to the midline of the body. Other common features include distinctive skull shapes, fontanelles (soft spots) that remain open longer than usual, and dental abnormalities. While CCD primarily affects skeletal and dental systems, it normally does not impact intelligence or life expectancy.
Symptoms & clinical features
The clinical features of cleidocranial dysplasia primarily involve skeletal and dental abnormalities. A key characteristic is hypoplasia (underdevelopment) or aplasia (absence) of the clavicles (collarbones), which can range from minor shortening to complete absence. This often results in unusually mobile shoulders that can be brought together in front of the chest [PMID:17718063]. The skull may exhibit a broad forehead, larger than average head size (macrocephaly), and delayed closure of the fontanelles (the soft spots on a baby's head).
Dental issues are frequently observed in individuals with CCD. These can include delayed eruption of permanent teeth, retention of baby teeth, and the presence of supernumerary (extra) teeth. Such dental anomalies can lead to malocclusion (misalignment of teeth) and difficulty with chewing. Additionally, some individuals may have a short stature, bone abnormalities in the hands and feet, or other less common skeletal findings [PMID:33608757].
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Affected organs
Cleidocranial dysplasia predominantly affects the skeletal system and teeth. The primary bones involved are the: * **Clavicles (collarbones):** These may be partially formed, underdeveloped, or entirely absent. * **Skull:** Features often include delayed closure of the fontanelles and sutures (fibrous joints connecting the bones of the skull), a prominent forehead, and a flattened bridge of the nose. * **Pelvis:** Pelvic abnormalities can sometimes occur. * **Spine:** Curvature of the spine (scoliosis) may be present in some cases.
Dental structures are also significantly impacted. This includes anomalies of both primary (baby) and permanent teeth, such as delayed eruption, impaction, and additional teeth. The central nervous system is typically not affected, and individuals with CCD usually have normal cognitive development.
Risks & severity
The severity of cleidocranial dysplasia can vary widely, even within the same family. Some individuals may have very mild features that are only discovered incidentally, while others may have more pronounced skeletal and dental issues. The dental complications, such as multiple unerupted teeth or supernumerary teeth, can lead to problems with eating and speech if not managed appropriately.
While CCD is a lifelong condition, it typically does not reduce life expectancy. Potential complications can include recurrent ear and sinus infections, mild hearing loss, and in some cases, osteoporosis (reduced bone density) later in life [PMID:17718063]. Spinal abnormalities, if present, can sometimes lead to issues with mobility. Early diagnosis and appropriate management can help to address many of the potential risks and improve quality of life.
Genetic causes
Cleidocranial dysplasia is caused by pathogenic variants in the *RUNX2* gene. This gene provides instructions for making a protein called runt-related transcription factor 2. The RUNX2 protein is a transcription factor, which means it helps control the activity of other genes. It plays a crucial role in the development and maintenance of bones and teeth [PMID:33608757].
When a pathogenic variant occurs in the *RUNX2* gene, the resulting protein may be non-functional, reduced in amount, or altered in a way that disrupts its normal role in regulating bone and dental development. This disruption leads to the characteristic features observed in individuals with CCD. Most cases of CCD are caused by a deletion or a specific point change in one copy of the *RUNX2* gene.
- RUNX2 RUNX family transcription factor 2The RUNX2 gene is essential for normal bone and tooth development, providing instructions for a protein that acts as a key regulator of bone-forming cell differentiation.
Inheritance pattern
Cleidocranial dysplasia is inherited in an autosomal dominant pattern. This means that a person only needs one altered copy of the *RUNX2* gene in each cell to develop the condition. If a parent has CCD, there is a 50% (1 in 2) chance with each pregnancy that their child will also inherit the altered gene and develop the condition, regardless of the child's sex.
Approximately 60% of cases are inherited from an affected parent, while the remaining 40% result from a new (de novo) pathogenic variant in the *RUNX2* gene that occurs for the first time in an individual with no family history of the condition. In such de novo cases, the parents are unaffected, but the affected individual can then pass the condition on to their children in an autosomal dominant manner.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosis of cleidocranial dysplasia is usually based on a combination of clinical evaluation, characteristic skeletal findings visible on X-rays, and confirmed by genetic testing. Clinical features such as absent or underdeveloped collarbones, typical facial characteristics, and dental anomalies raise suspicion for CCD.
Radiographic imaging (X-rays) is a critical diagnostic tool, revealing features like delayed closure of fontanelles, underdeveloped collarbones, and pelvic abnormalities. Genetic testing, specifically sequencing of the *RUNX2* gene, can confirm the diagnosis by identifying a pathogenic variant. In the UK, genetic testing for suspected cases of cleidocranial dysplasia may be accessed through the NHS Genomic Medicine Service, often following referral from a specialist clinician to a clinical genetics service. This process may be associated with NHS R-codes such as R109 Skeletal Dysplasia - Known Familial and R132 Skeletal Dysplasia - Unspecified.
Management & lifestyle
Management for individuals with cleidocranial dysplasia focuses on addressing specific symptoms and can involve a multidisciplinary team of healthcare professionals. Regular dental care is crucial due to the complex dental issues, often requiring orthodontic treatment, oral surgery to remove supernumerary teeth, and dental implants or dentures [PMID:17718063].
Skeletal issues typically do not require extensive intervention, though monitoring for spinal curvature or hip problems may be recommended. Physiotherapy can help maintain shoulder strength and mobility if the collarbones are severely affected. In the UK, management will typically be coordinated by a paediatrician or a geneticist, who can refer to relevant specialists. Individuals and families can also benefit from genetic counselling to understand the condition, its inheritance, and implications for family planning.
UK care pathway
In the UK, individuals suspected of having cleidocranial dysplasia are typically referred to a clinical genetics service or a paediatrician for assessment. The NHS Genomic Medicine Service provides diagnostic genetic testing capabilities, often guided by specific R-codes relevant to skeletal dysplasias. Genetic counsellors play a vital role in explaining the genetic basis of the condition, inheritance patterns, and reproductive options. This integrated approach ensures comprehensive care and support for affected individuals and their families.
Frequently asked questions
What is the life expectancy for someone with cleidocranial dysplasia?
Cleidocranial dysplasia typically does not affect life expectancy. Individuals with the condition usually have a normal lifespan, though they may require ongoing medical and dental care to manage their symptoms.
Can cleidocranial dysplasia be detected before birth?
In some cases, severe skeletal features like underdeveloped collarbones or open fontanelles might be noted during prenatal ultrasound scans. If a family history of CCD exists, prenatal genetic testing can be an option to confirm the diagnosis before birth.
How does cleidocranial dysplasia affect teeth?
Dental problems are common with CCD, including delayed eruption of permanent teeth, baby teeth that don't fall out, and extra (supernumerary) teeth. These issues often require extensive dental and orthodontic treatment to correct.
Is surgery typically needed for cleidocranial dysplasia?
Surgery is not typically needed for the collarbone issues, as the increased shoulder mobility usually does not cause functional problems. However, oral surgery is often required for dental issues, such as removing extra teeth or assisting with tooth eruption.
Will my child's intellectual development be affected?
No, cleidocranial dysplasia does not typically affect intellectual development. Individuals with the condition usually have normal cognitive abilities.
References
- Franceschi R, Stringari G, Soli F. Newborn with cleidocranial dysplasia. Skeletal radiology. 2022. PMID: 35727340
- Kutilek S, Machytka R, Munzar P. Cleidocranial dysplasia. Sudanese journal of paediatrics. 2019. PMID: 31969747
- Adam MP, Bick S, Mirzaa GM. Cleidocranial Dysplasia Spectrum Disorder. 1993. PMID: 20301686
- Pirinen S. Genetic craniofacial aberrations. Acta odontologica Scandinavica. 1998. PMID: 10066116
- Siddique AW, Ahmed Z, Haider A. Yunis-Varon Syndrome. Journal of Ayub Medical College, Abbottabad : JAMC. 2019. PMID: 31094135
- Jaruga A, Hordyjewska E, Kandzierski G. Cleidocranial dysplasia and RUNX2-clinical phenotype-genotype correlation. Clinical genetics. 2016. PMID: 27272193
- Pan CY, Tseng YC, Lan TH. Craniofacial features of cleidocranial dysplasia. Journal of dental sciences. 2017. PMID: 30895069
- Mundlos S. Cleidocranial dysplasia: clinical and molecular genetics. Journal of medical genetics. 1999. PMID: 10204840