Cleidocranial Dysplasia: Definition, Causes, Symptoms, Diagnosis and Treatment

It is a condition that mainly affects the development of bones and teeth.

It is a genetic disorder caused by the mutation of a gene

Causes of cleidocranial dysplasia

Cleidocranial dysplasia is usually caused by mutations in the RUNX2 gene that contains instructions for the production of a protein involved in the development and maintenance of teeth, bones, and cartilage.

Most of the cartilage later turns into bone, through a process called ossification, with the exception of the cartilage that continues to cover and protect the ends of the bones and is present in the nose, airways, and outer ears.

Researchers believe that the RUNX2 protein acts as a “master switch,” regulating a number of other genes involved in the development of bone-forming cells ( osteoblasts ) and the development of teeth.

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 decrease interferes with the normal development of bones, cartilage, and teeth.

In rare cases, individuals with a deletion of genetic material that includes RUNX2 and other nearby genes may experience additional characteristics, such as developmental delay, as a result of the loss of these genes.

Cleidocranial dysplasia is transmitted in an autosomal dominant pattern, meaning that a single copy of the altered gene from both parents results in the condition.

But cases have also been detected in which the patient has only one parent with the defective gene and is affected by cleidocranial dysplasia.

When only one parent has the mutated gene, the patient will often end up with a mild form of the condition that may go undiagnosed.

On the other hand, spontaneous mutations in the gene leading to cleidocranial dysplasia can occur, even if both parents are not carriers of the mutation.

Those individuals with a family history of the disease should undergo genetic testing to know what to expect.

Symptoms of cleidocranial dysplasia

The signs and symptoms of cleidocranial dysplasia can vary widely in severity, even within the same family.

People with cleidocranial dysplasia usually have underdeveloped or absent clavicles.

As a result, their shoulders are narrow and sloping, they can be unusually joined together in front of the body, and in some cases they can be made to meet in the middle of the body.

Late maturation of the skull is also characteristic of this condition, including delayed closure of growth lines where the skull bones meet (sutures) and larger-than-normal spaces (fontanelles) between the skull bones that are noticeable as “Soft.”

Fontanelles normally close in early childhood, but they can remain open throughout life in people with this disorder.

Some people with cleidocranial dysplasia have extra pieces of bone called Wormian bones inside the sutures.

Affected individuals are usually smaller than other members of the same family at the same age.

They also have short tapered fingers and broad thumbs, flat feet, bowed legs or knees, short shoulder blades (scapulae), and an abnormal curvature of the spine (scoliosis).

Typical facial features include a short, broad skull (brachycephaly), the presence of a prominent forehead, wide-open eyes (hypertelorism), a flat nose, and a small upper jaw.

People with cleidocranial dysplasia often have decreased bone density (osteopenia) and can develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture, at a relatively young age.

Dental abnormalities are very common in cleidocranial dysplasia and can include delayed loss of primary (baby) teeth and late appearance of secondary (adult) teeth.

An unusual shape, peg-shaped teeth, misalignment of the teeth, extra teeth and jaws with malocclusion and sometimes accompanied by cysts in the gums are observed.

Other possible complications can include an increased risk of ear infections, sinusitis, upper respiratory tract infections, and even hearing loss due to fluid build-up in the middle ear, you may also suffer from vision problems.

Some children may have mild delays in the development of their motor skills, such as crawling and walking, but their intelligence is not affected.

Diagnosis

Cleidocranial dysplasia can be diagnosed before or after the baby is born.

Before birth, the diagnosis is made through an analysis of DNA extracted from the fetus. This can be achieved in one of the following ways:

  • By amniocentesis after the 15th week of pregnancy.
  • By chorionic villus sampling between week 11 and 14 of pregnancy.

These methods are used for high-risk pregnancies, for example, if the parents have another child diagnosed with cleidocranial dysplasia or if one of the parents has cleidocranial dysplasia.

To be eligible for this test, you must know the mutations in the gene responsible for causing cleidocranial dysplasia in the family.

This means that genetic testing (a blood test) should be performed on the person and family with cleidocranial dysplasia.

Cleidocranial dysplasia can be diagnosed before birth using ultrasound to look for features of the disease.

The diagnosis of cleidocranial dysplasia, when made after birth, is based on x-ray results and a physical exam.

A diagnosis of cleidocranial dysplasia can be confirmed by a DNA test of the RUNX2 genes (a blood test).

Treatment of cleidocranial dysplasia

Children with cleidocranial dysplasia can lead satisfactory lives if they receive thoughtful and informed care from their parents and doctors.

The treatment of cleidocranial dysplasia is based on early detection and management of symptoms and complications. People with cleidocranial dysplasia have a normal life expectancy.

Treatment of dental problems

Early referral to a dental clinic familiar with cleidocranial dysplasia allows for timely planning of necessary procedures. The goal of treatment is:

  • Improve the appearance of the teeth.
  • Improve chewing ability

This can be accomplished through a combination of dental procedures that may include surgery.

Speech therapy

Speech therapy is sometimes necessary during the dental treatment process.

Treatment of recurrent infections

Sinus and ear infections need prompt treatment with proper medication.

Head injury prevention

If the individual has large openings between the skull bones (fontanelles), the head must be protected from blunt trauma. The child should wear helmets during high-risk activities such as biking, rollerblading, and playing baseball.

Calcium and vitamin D supplements

If the individual has low bone density (osteoporosis), the doctor may suggest calcium and vitamin D supplements to strengthen the bones.

Follow-up of pregnant women

Pregnant women with cleidocranial dysplasia should be carefully monitored, including sometimes a cesarean section is necessary for delivery.