Cleidocranial Dysplasia

Cleidocranial dysostosis is a rare condition involving dysplasia, or abnormal development, of specific bones in the body.  Cleidocranial dysostosis (cleidocranial dysplasia) is very rare, occurring in approximately 1 in 1,000,000 individuals.  The condition is characterized by a large, open fontanelle (soft spot in the skull), underdevelopment of the facial bones, abnormal teeth, and hypoplasia (underdevelopment) of the clavicles. CCD is also known as cleidocranial dystosis or Marie-Sainton Syndrome, and occurs in approximate 1 in 1 million individuals.

Signs and Symptoms of Cleidocranial Dysplasia

Individuals with CCD typically have a normal life expectancy and normal intelligence, but many physical features characterize the condition. Symptoms can vary greatly, even within the same family. Typically, individuals with CCD exhibit some combination of skeletal, facial, and dental abnormalities.

• Skeletal features of CCD

  • Delayed closure of the skull bones (typically in adulthood rather than as a child)
  • Underdeveloped or absent collarbones resulting in narrow, sloping shoulders
  • Premature closure of the coronal suture
  • Scoliosis
  • Short stature (usually 3 – 6 inches shorter than other family members)
  • Short forearms
  • Short, tapered fingers and broad thumbs
  • Abnormal shape of the pelvic bone
  • Flat feet
  • Knock knees

• Facial characteristics of CCD

  • Wide nasal bridge
  • Wide-spaced eyes (hypertelorism)
  • Protruding jaw
  • Protruding brow

• Dental abnormalities of CCD

  • Delayed loss of baby teeth
  • Delayed eruption of adult teeth
  • Deformed or unusually shaped  teeth
  • Crooked or misaligned teeth (malocclusions)
  • Extra teeth

Causes of Cleidocranial Dysplasia

Cleidocranial dysostosis is caused by a mutation in the gene RUNX2, or runt-related transcription factor.  This gene is important in the differentiation and development of osteoblasts (cells that make bone), and in development of the skeleton.  Cleidocranial dysostosis is inherited in an autosomal dominant manner, meaning that only one copy of the gene is necessary to develop the disease.  This means that a parent with cleidocranial dysostosis has a 50% chance that their child will have the disease.  Alternatively, the mutation may occur sporadically, without inheriting the abnormal gene from a parent.

What is affected in patients with cleidocranial dysostosis?

Patients with cleidocranial dysostosis may have a number of developmental anomalies related to hypoplasia of specific bones.  In the skull, the anterior fontanelle (soft spot) is frequently large at birth, and may remain open even through adulthood.  This leads to a broad forehead and a persistent bony gap.  The mid-face, or upper jaw, may be hypoplastic, or underdeveloped.  Patients frequently have dental anomalies, such as delayed eruption of secondary or “grown-up” teeth, lack of shedding of primary or “baby” teeth, dental crowding, and supernumary (extra) teeth.  The clavicles, or collarbones, are frequently hypoplastic, leading to sloping shoulders which can often touch each other at the midline.  There may be hand abnormalities, such as brachydactyly (short fingers) and short, broad thumbs.  Patients may develop other skeletal anomalies, such as pes planus (flat feet) or scoliosis.  Patients may have recurrent sinus infections, and approximately 1/3 develop hearing loss.  Intelligence and development tend to be normal.  Patients tend to be shorter than their unaffected siblings.

Complications Associated with Cleidocranial Dysplasia

The various bone and dental deformities associated with CCD can cause complications for individuals with this condition.

• Decreased bone density leading to osteoporosis
• Hearing loss
• Recurrent ear and sinus infections
• Mild delay in development of motor skills, such as crawling or walking
• Loose joints
• Chewing and eating problems due to dental abnormalities
• High rate of caesarean sections for women, due to an abnormally shaped pelvis

Diagnosis of Cleidocranial Dysplasia

Diagnosis of cleidocranial dysostosis is based on physical examination, supported by radiographic findings (x-rays and CT scans) and genetic testing. The condition can be diagnosed before or after birth. DNA may be taken from the fetus for testing. This is typically only done for high-risk pregnancies, when one parent has CCD. It may also be diagnosed using ultrasound to look for specific features of the condition. After birth, CCD is diagnosed using x-ray and physical exam. A blood test to specifically look at the DNA of the RUNX2 gene can also confirm the diagnosis.

Treatment for Cleidocranial Dysplasia

Fortunately, there have been many advances and improvements in treatments for CCD. Children with CCD can live fulfilling lives, with support and treatment to manage the various symptoms and complications. Management of the orofacial manifestations of CCD can be challenging and requires careful planning and execution by a team of oral and craniofacial surgeons, as well as specialized dentists and orthodontists. Successful treatment is based on early detection and intervention, but typically continues until growth has stopped.  Some common treatments include:

• Dental surgery and orthodontic treatments to improve appearance and the ability to chew
• Timely treatment and medication for recurrent ear and sinus infections
• Protective helmets to prevent head injuries in children with large openings between the skull bones
• Calcium and Vitamin D supplements for osteoporosis
• Craniofacial surgery for features such as hypertelorism

Treatment of patients with cleidocranial dysostosis requires a multidisciplinary approach, with team members including dentists, orthodontists, craniofacial surgeons, otolaryngologists (ear nose and throat doctors), orthopedic surgeons, and geneticists.  After presumptive diagnosis, imaging (xrays) are performed of the entire skeleton.  The patient is referred to a geneticist for evaluation and counseling.  Patients receive audiologic (hearing) evaluations, and ear evaluations by the ENT team.

During childhood, the patient is treated by the dental and orthodontics teams for management of the supernumerary (extra) teeth and assisting the permanent teeth in erupting (growing) and positioning.  Patients are assessed regularly by the ENT team, and tympanostomy tubes (ear tubes) are placed when necessary.  Bone density is followed, and patients are treated with calcium and vitamin D.  Some patients, later in childhood, may benefit from orthognathic (jaw) surgery and treatment of the skull defect.  Because of the underdeveloped upper jaw, patients are monitored for breathing disturbances, particularly when sleeping, and treated when needed.

Please contact the Craniofacial Team of Texas if you would like to schedule an appointment.

If you would like more information about this craniofacial anomaly, please contact the Craniofacial Team of Texas by calling 512-377-1142 or toll free 877-612-7069 to schedule an appointment or complete an online appointment request.