Cleidocranial Dysplasia Spectrum Disorder

Excerpt

Clinical characteristics: Cleidocranial dysplasia (CCD) spectrum disorder is a skeletal dysplasia that represents a clinical continuum ranging from classic CCD (triad of delayed closure of the cranial sutures, hypoplastic or aplastic clavicles, and dental abnormalities), to mild CCD, to isolated dental anomalies without other skeletal features. Individuals with classic CCD spectrum disorder typically have abnormally large, wide-open fontanelles at birth that may remain open throughout life. Clavicular hypoplasia can result in narrow, sloping shoulders that can be opposed at the midline. Moderate short stature may be observed, with most affected individuals being shorter than their unaffected sibs. Dental anomalies may include delayed eruption of secondary dentition, failure to shed the primary teeth, and supernumerary teeth. Individuals with CCD spectrum disorder are at increased risk of developing recurrent sinus infections, recurrent ear infections leading to conductive hearing loss, and upper airway obstruction. Intelligence is typically normal.

Diagnosis/testing: The diagnosis of CCD spectrum disorder is established in an individual with typical clinical and radiographic findings and/or a heterozygous pathogenic variant in RUNX2 identified by molecular genetic testing.

Management: Treatment of manifestations: If the cranial vault defect is significant, the head needs protection from blunt trauma; helmets may be used for high-risk activities. Surgical cosmesis for depressed forehead or lengthening of hypoplastic clavicles can be considered. Careful planning of anesthetic management due to craniofacial and dental abnormalities. Consultation with an otolaryngologist to assist in securing the airway. Consideration of alternative anesthetic approaches, including neuraxial block, taking into account possible spine abnormalities. If bone density is below normal, treatment with calcium and vitamin D supplementation. Dental procedures to address retention of primary dentition, presence of supernumerary teeth, and non-eruption of secondary dentition. Such procedures may include prosthetic replacements, removal of the supernumerary teeth followed by surgical repositioning of the secondary teeth, and a combination of surgical and orthodontic measures for actively erupting and aligning the impacted secondary teeth. Speech therapy as needed. Aggressive treatment of sinus and middle ear infections; consideration of tympanostomy tubes for recurrent middle ear infections; regular immunizations including influenza. Sleep study in those with manifestations of obstructive sleep apnea; surgical intervention may be required for upper airway obstruction.

Surveillance: Monitor children for orthopedic complications, dental abnormalities, sinus and ear infections, upper airway obstruction, hearing loss, and speech issues. DXA scan to assess bone mineral density beginning in early adolescence and every five to ten years thereafter.

Agents/circumstances to avoid: Helmets and protective devices should be worn when participating in high-risk activities.

Pregnancy management: Monitor affected women during pregnancy for cephalopelvic disproportion.

Genetic counseling: CCD spectrum disorder is inherited in an autosomal dominant manner. The proportion of individuals with CCD spectrum disorder caused by a de novo pathogenic variant is high. Each child of an individual with CCD spectrum disorder has a 50% chance of inheriting the RUNX2 pathogenic variant. Once the RUNX2 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing for CCD spectrum disorder are possible.