Cleidocranial dysplasia (referred to as CCD in this review) is a skeletal dysplasia characterized by delayed closure of the cranial sutures, hypoplastic or aplastic clavicles, and multiple dental abnormalities. Manifestations may vary among individuals in the same family. The most prominent clinical findings are abnormally large, wide-open fontanels at birth that may remain open throughout life; mid-face hypoplasia; abnormal dentition, including delayed eruption of secondary dentition, failure to shed the primary teeth, supernumerary teeth with dental crowding, and malocclusion; clavicular hypoplasia resulting in narrow, sloping shoulders that can be apposed at the midline; and hand abnormalities such as brachydactyly, tapering fingers, and short, broad thumbs. Individuals with CCD are shorter than their unaffected sibs and are more likely to have other skeletal/orthopedic problems such as pes planus, genu valgum, and scoliosis. Other medical problems include recurrent sinus infections and other upper-airway complications, recurrent ear infections, high incidence of cesarean section, and mild degree of motor delay in children under age five years.
Diagnosis of CCD is based on clinical and radiographic findings that include imaging of the cranium, thorax, pelvis, and hands. RUNX2 (CBFA1) is the only gene known to be associated with CCD. Molecular genetic testing of the RUNX2 gene detects mutations in 60%-70% of individuals with a clinical diagnosis of CCD. Such testing is available on a clinical basis.
Cleidocranial dysplasia is inherited in an autosomal dominant manner. The proportion of cases caused by a de novo mutation is high. Each child of an individual with CCD has a 50% chance of inheriting the mutation. Prenatal diagnosis for pregnancies at increased risk is possible if the disease-causing mutation in the family is known.