What Is Cleidocranial Dysplasia?
Cleidocranial dysplasia is a rare autosomal dominant disorder that affects the bones, skull, and teeth. It is otherwise known as:
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Cleidocranial dysostosis.
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Dento-osseous dysplasia.
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Marie-Santon syndrome.
What Is the Frequency of Cleidocranial Dysplasia?
It is estimated that about 1 in one million people has cleidocranial dysplasia worldwide. It is also likely that some individuals are not diagnosed as they have mild signs and symptoms.
What Is the Cause of Cleidocranial Dysplasia?
A mutation in the RUNX2 gene mainly causes cleidocranial dysplasia. This gene is responsible for developing and maintaining teeth, bones, and cartilage. Hence, there is an interference in the normal development of the bones, cartilage, and teeth, leading to clinical manifestation. Additional features such as developmental delay will also be experienced when there is a deletion in the nearby genes. In about 30 percent of individuals, there is no mutation in the RUNX2 gene. The cause is not known in such individuals.
What Are the Clinical Features of Cleidocranial Dysplasia?
Classic CCD- The most important clinical features of cleidocranial dysplasia include:
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A triad of underdeveloped or absent collarbones (clavicles).
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Dental abnormalities like broad mandible, supernumerary teeth, high arched palate.
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Delayed closure of the spaces between the skull bones (fontanelles). Sometimes, the fontanelles do not close at all.
There can be other associated features which include-
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Dental anomalies like a failure in the eruption of permanent teeth.
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Decreased bone density (osteopenia) can lead to osteoporosis (a condition that can make bones progressively more brittle and prone to fracture).
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Hearing loss.
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Bone abnormalities of the hands.
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Upper airway obstruction.
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Recurrent sinus and ear infections.
Affected individuals are usually shorter than the rest of their family members, have short, tapered fingers, flat feet, abnormal curvature of the spine (scoliosis), and broad thumbs.
Some of the standard facial features include a wide short skull (brachycephaly), a prominent forehead, wide eyes (hypertelorism), a flat nose, and a small upper jaw. Intelligence is usually normal.
What Are the Radiographic Features of Cleidocranial Dysplasia?
The following radiographic features of the skull include-
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Multiple wormian bones (the abnormal bone that develops within the skull).
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Widened sagittal sutures or fontanelles.
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Frontal or parietal bossing.
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Supernumerary, impacted crowded or abnormal teeth.
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Abnormal ear structures that result in hearing loss.
Chest:
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Cone-shaped thorax.
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Hypoplasia or absent clavicles.
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Supernumerary ribs.
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High scapulae.
Pelvis:
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Hypoplasia of iliac bones.
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Absent or delayed ossification of the pubic bone.
Limbs:
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Short or absent fibula.
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Short or absent radius.
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Hypoplastic terminal phalanges.
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Pseudoepiphysis of metacarpals and metatarsal bones.
How to Diagnose Cleidocranial Dysplasia?
The diagnosis is based on the symptoms, clinical examination, imaging studies, and genetic testing for the pathogenic variant in the RUNX2 gene. The above clinical and radiological findings are suggestive of cleidocranial dysplasia. The molecular testing approach includes single-gene testing, karyotype, or the use of a multigene panel.
Classic cleidocranial dysplasia can be diagnosed by ultrasound examination in the fetus of an affected parent as early as 14 weeks of gestation.
To come to a conclusion on the extent of disease and needs in a person diagnosed with cleidocranial dysplasia, the following evaluations are necessary-
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A complete skeletal survey, including hands and feet, is necessary.
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DXA (dual-energy X-ray absorptiometry) scan is suggested for those in early adolescence and older.
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Dental evaluation by a dentist who knows this condition in detail and its management.
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Tests for hearing loss.
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Consultation with a genetic counselor.
How to Manage Cleidocranial Dysplasia?
1) Craniofacial:
Proper evaluation by a craniofacial surgeon and rehabilitation is necessary. In most individuals, the fontanelles close with time, and cranial remodeling is not required. However, if the cranial vault defect is significant, the head should be protected from blunt trauma. Helmets may be advised for high-risk activities.
2) Skeletal:
Calcium and vitamin D supplementation treatment is necessary if the bone density is below normal in the DXA scan.
The affected individual may consider correcting the depressed forehead and lengthening the clavicle for cosmetic reasons.
3) Dental:
The goal is to improve the appearance and provide a proper functioning masticatory mechanism. It can be done by combining surgical and orthodontic measures, including extractions, prosthetic replacements, surgical repositioning of the permanent teeth.
Speech therapy may be required during periods of dental treatment.
4) Upper Airway Obstruction:
A sleep study is indicated when symptoms suggest upper airway obstruction, and surgical intervention is required.
5) Sinus and Middle Ear Infection:
In case of these infections, aggressive and timely treatment is necessary.
6) Endocrinology:
Improvements after growth hormone therapy for short stature have not yet been proven.
7) Prevention of Primary Complications:
Since most of the bone mineral density is achieved in the second and third decades, preventive treatment for osteoporosis should be started at a young age. Early screening for low mineral density and appropriate vitamin D and calcium supplementation is recommended.
8) Prevention of Secondary Complications:
Anesthetic management should be carefully planned as some individuals have difficulty nasal breathing.
9) Evaluation of Relatives at Risk:
It is appropriate to offer genetic counseling to young adults who are affected. Genetic counseling is the process of providing individuals and families with information on the nature, mode of inheritance, and implications of genetic disorders to help them make informed medical and personal decisions.
Conclusion:
Individuals with cleidocranial dysplasia are born with congenital defects due to mutations in the gene that provide instructions for making the proteins involved in the development and maintenance of teeth, bones, and cartilage. The extent of the severity can vary within the same family. Treatment is mainly focused on managing the symptoms, and most people require treatment from different specialties like a craniofacial surgeon, dentist, orthodontist, endocrinologist, otolaryngologist, and orthopedist.