Cleidocranial Dysplasia Causes

What is Cleidocranial Dysplasia?

The word ‘cleido’ refers to collarbone or clavicles, ‘cranial’ refers to the skull bones or cranium, and ‘dysplasia’ means abnormal growth. Thus, it is a condition characterized by the abnormal growth of collarbones and skull. Other names for this disorder include Cleidocranial Dysostosis, Dento-Osseous Dysplasia, and Maria- Sainton Syndrome.

Cleidocranial Dysplasia is an extremely rare disease seen in one in a million cases of live births. So far, only about a thousand recorded cases have been studied in the medical literature. The symptoms of the medical condition vary from being extremely severe to very mild. The babies with mild symptoms are often not diagnosed at birth if the symptoms are mild and no obvious defects are visible at birth.

What Causes Cleidocranial Dysplasia?

Cleidocranial Dysplasia is a genetic disorder caused by a mutation in the RUNX2 gene.  The RUNX2 gene encodes for the protein required for the development of teeth, bones, and cartilage. As this protein also regulates several other genes instrumental in the building of bones and development of teeth, it is called a ‘master switch’ protein.

Mutation in the RUNX2 gene causes reduction or complete elimination of this master switch protein resulting in the abnormal development of bones, teeth and cartilage leading to cleidocranial dysplasia. Although mutation in the RUNX2 gene is the main cause of this condition, there is no mutation seen in the RUNX2 gene in 30% patients with cleidocranial dysplasia. The cause of the disorder is unknown in these cases.

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Understanding the Genetic Inheritance Pattern

Cleidocranial Dysplasia is passed on by an autosomal dominant pattern which means that a single copy of the altered gene from both parents results in the condition. However, it is also possible for the patient to have only one parent with the defective gene and still get affected by the condition. As it is genetically inherited, changes in maternal nutrition or lifestyle cannot prevent this disease. Genetic counselling of parents with the condition is important.

When only one parent has the mutated gene, the patient will often end up with a mild form of the condition which may go undiagnosed. On the other hand, spontaneous mutations in the gene may occur leading to cleidocranial dysplasia even if both parents are not carriers of the mutation. Those with a family history of the condition must undergo genetic testing to know what to expect.

Related Disorders

There are other disorders with symptoms similar to cleidocranial dysplasia. Many of them are also autosomal recessive genetic disorders with more than one symptom in common. All these conditions should be considered and compared before a formal diagnosis is made. Here we discuss four of them.

Mandibuloacral Dysplasia – A rare disorder characterized by limited joint movement, slow growth of the jaw, discernible spaces between the skull bones, atrophic skin, underdeveloped fingers and collarbone. There may be a defect in the hip, causing thigh bones to jut out at an angle to the side of the body leading to a condition known as coxa valga.

Pyknodysostosis – Another rare genetic disorder which affects males and females equally. It is characterized by delayed suturing of the skull bones, high density of bones, short stature, underdeveloped fingers and jaw. The chin is often receding and a number of dental problems may also be seen. The skeletal system also displays many abnormalities.

Osteogenesis Imperfecta – This rare disease tends to run in families as an autosomal dominant trait.  The disorder is characterized by issues in the connective tissue as well as very fragile bones. The patient has brittle bones that often get fractured with the minimal application of force or trauma. The severity of the disorder can vary significantly from a mild disorder to an extremely severe version which has a number of related complications.

Hajdu-Cheney Syndrome – Another rare connective tissue disorder that runs in families. The fibrous tissue that supports joints and other body parts is known as connective tissue. In this disease, the patient is often seen with ulcerating lesions on the hands and feet. Acroosteolysis, or the softening and destruction of bones also occurs. The teeth, bones, and joints may show signs of abnormalities in this condition.

Sources

Further Reading

Last Updated: Oct 11, 2022

Cashmere Lashkari

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Cashmere Lashkari

Cashmere graduated from Nowrosjee Wadia College, Pune with distinction in English Honours with Psychology. She went on to gain two post graduations in Public Relations and Human Resource Training and Development. She has worked as a content writer for nearly two decades. Occasionally she conducts workshops for students and adults on persona enhancement, stress management, and law of attraction.

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