Cleidocranial Dysplasia

 Cleidocranial Dysplasia

DISEASE OVERVIEW

Cleidocranial dysplasia is a rare genetic disorder characterized by abnormal bone formation commonly affecting the skull, teeth and long bones. As a result, short stature, distinctive facial features and narrow, sloping shoulders caused by abnormally developed or absent collarbones (clavicles) may be present in affected individuals. Major features may include premature closing of the soft spot on the head (coronal), delayed closure of the space between the bones of the skull (fontanels), narrow and abnormally shaped pelvic and pubic bones and abnormalities in development of the chest (thoracic region). If not diagnosed at birth, clinical presentation of remarkable features may be most notable in early childhood or adolescence. Additionally, a high arched palate, failure of the lower jaw joints to unite, delayed eruption of teeth and fingers that are irregular in length may also be present. Cleidocranial dysplasia is inherited as an autosomal dominant genetic condition. Approximately 1,000 cases of this disorder have been reported in the medical literature.

SIGNS & SYMPTOMS

Because affected individuals can present with an array of features related to cleidocranial dysplasia, it is not always diagnosed at birth. The most prominent feature of cleidocranial dysplasia is the absence of collarbones or narrow, drooping shoulders caused by complete or partial absence of the collarbones. There may be abnormalities of the muscles in the area of the collarbones associated with an irregularly wide range of shoulder movement in affected individuals with collarbone abnormalities. Another prominent feature is atypical skull formation or skull abnormalities, which may include a premature closure of the two soft spots on the head (fontanels) and the fibrous joints where bones of the skull meet (sutures) causing abnormal development of the skull. Distinct facial features typically include a prominent forehead, unusually wide face, prominent chin, small upper jaw (maxillary hypoplasia) and bulging of the skull cap. Most individuals with cleidocranial dysplasia have some but not necessarily all features listed above and are diagnosed between birth and adolescence as the child develops and abnormalities may become more noticeable over time (irregular growth of long bones or pelvis, atypical facial feature development, abnormal tooth or jaw formation, etc.).

Other bone abnormalities that have been found in some patients with cleidocranial dysplasia may be: a wide pelvic joint, delayed growth of the pubic bone, a hip defect in which the thigh bone angles towards the center of the body (coxa vara), failure of the lower jaw bones to unite, a defect of the hip that causes the thigh bone to angle out to the side of the body (coxa valga), curvature of the spine (scoliosis), a small shoulder blade and/or curvature of the upper legs so that the knees appear unusually close together (genu valgum).

Dental abnormalities may include: a delay in tooth eruption, incomplete development or absence of teeth, underdeveloped enamel and/or extra teeth. Cysts may form around the unerupted or displaced teeth in some people. A high-arch palate or a condition in which there is a hole in the roof of the mouth (cleft palate) may be present.

Individuals with cleidocranial dysplasia have an increased risk for recurrent ear and sinus infections, upper respiratory complications and hearing loss.

CAUSES

Cleidocranial dysplasia is caused by changes (mutations or pathogenic variants) in the RUNX2 gene (originally called the CBFA1 gene). This gene codes for a protein that affects bone development and the proliferation of healthy osteoblasts. Osteoblasts are the specific cell type that make up bones and contribute to proper bone formation in the body. RUNX2 is a transcription factor or regulator of osteoblast generation in the body termed osteogenesis. About 20-30% of individuals with cleidocranial dysplasia do not have a pathogenic variant in the RUNX2 gene. This suggests that there are other genetic causes of this condition.

Cleidocranial dysplasia is a rare disorder that is usually inherited as an autosomal dominant genetic condition. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a changed (mutated) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.

DISORDERS WITH SIMILAR SYMPTOMS

Symptoms of the following disorders can be similar to those of cleidocranial dysplasia. Comparisons may be useful for a differential diagnosis:

Mandibuloacral dysplasia is a rare disorder that may be characterized by a limitation in joint movement, slowed growth of the jaw, atrophic skin, underdeveloped fingers, a wide space between the bones of the skull, limited joint movement, absent or underdeveloped collarbone and/or a hip defect in which the thigh bone angles out to the side of the body (coxa valga). Mandibuloacral dysplasia is thought to affect males and females equally. Although these features may overlap with those present in individuals with cleidocranial dysplasia, mandibuloacral dysplasia is inherited in an autosomal recessive manner.

Pyknodysostosis is a very rare genetic disorder that may be characterized by a delay in closure of the skull bones, short stature, an increase in the density of the bones, an underdeveloped jaw and abnormalities of the fingers. A small receding chin, dental abnormalities and short arms and legs may also be present. This disorder affects males and females equally and is inherited in an autosomal recessive manner.

Osteogenesis imperfecta (OI) is a group of rare disorders affecting the connective tissue and characterized by extremely fragile bones that break or fracture easily (brittle bones), often without apparent cause. Connective tissue is strong fibrous tissue that supports and joins other body tissues and parts. The specific symptoms and physical findings associated with OI vary greatly from person to person. The severity of OI varies even among individuals in the same family. OI may be a mild disorder or may result in severe complications. In most cases, osteogenesis imperfecta is inherited as an autosomal dominant condition.

Hajdu-Cheney syndrome is a rare connective tissue disorder. The most distinctive feature of individuals with this disorder is the appearance of ulcerating lesions on the palms of the hands and soles of the feet accompanied by softening and destruction of bones (acroosteolysis). Abnormal development of bones, joints and teeth also occurs. A decrease in bone mass and changes in the skull and jawbone are also features of this syndrome. The majority of cases are of unknown cause, but multiple cases have been reported in families which suggests autosomal dominant genetic inheritance.

Treatment

There is no cure for cleidocranial dysplasia. However, certain symptoms and features may be treated as they become apparent. Head gear in the form of a baby helmet may be worn after birth to protect the skull bones until they close. If dental abnormalities are present, appropriate dental care should be provided such as attending to tooth deformation or mandibular abnormalities possibly with surgical intervention. If a cleft palate is present, surgery may also be performed to close or block the opening to improve quality of life. Hearing evaluations should be performed at birth and throughout childhood since hearing complications may be present in individuals with cleidocranial dysplasia.

Affected individuals have an increased risk for sleep apnea, sinus infections and ear infections due to delayed craniofacial development and should be assessed for symptoms that may require treatment as needed. Overall bone density should also be monitored over time and treatment provided if indicated. Speech and language may need to be assessed by a speech pathologist.

Genetic counseling is recommended for patients and their families. Other treatments are dependent on symptoms and supportive as needed due to the variety of effects this condition can have on the body as mentioned above.

TYPE OF DOCTOR AND DEPARTMENT: Orthopaedics SPECIALIST CAN DIAGNOSE THIS DISEASE.