Cleidocranial Dysplasia

Generalized skeletal dysplasia resulting in defects in the development of skull, clavicles, pelvis, and teeth.

Cleidocranial Dysostosis; Scheuthauer-Marie-Sainton Syndrome; Marie-Sainton Syndrome.

More than 500 cases have been reported worldwide. No sexual predilection.

Autosomal dominant. There is a wide variability in expression.

The disorder is caused by mutations in the transcription factor CBFA1 of the runt domain gene family. The responsible gene has been mapped to 6p21. This situation results in generalized dysplasia of bone and dental tissue. Initially it was postulated that the disease affects only the membranous bones (neurocranium, a portion of the clavicle, and some facial bones). However, we now know that cleidocranial dysplasia is a generalized skeletal dysplasia. There is growth retardation and a slight effect on skeletal maturation over time.

Based on the clinical findings of skull, dental, pelvic, and clavicular malformations and confirmed with genetic mapping. Radiographs show persistently open skull sutures and fontanelle with bulging of the calvarium, short fifth finger middle phalanx, and characteristic bone changes.

The disease involves mainly the head and neck (brachycephaly, enlarged calvaria, frontal bossing with wide forehead and hypertelorism, wormian bones, large foramen magnum, hypoplasia or absence of frontal and paranasal sinuses, midfacial hypoplasia, micrognathia, nonunion of mandibular symphysis, high arched palate or cleft palate, delayed eruption of deciduous and permanent teeth, enamel and root hypoplasia, cavities, supernumerary teeth [up to 30 extra teeth have been described], and deafness) and the skeleton (short stature, spina bifida occulta, [unilateral or bilateral] hypoplastic [more often at the acromial than at the sternal end] or aplastic [rare] clavicles with the ability to appose the shoulders, narrow, bell-shaped thorax with short, oblique ribs, cervical ribs, small scapula with dysplastic acromial facets and supraspinatus fossae, hypoplastic pubic bones with widened symphysis pubis, hip dislocation, generalized joint laxity, brachydactyly, excessive length of metacarpal and metatarsal II (and V) bones secondary to extra epiphyses, short middle phalanx of the fifth fingers, cup-shaped and hypoplastic distal phalanges with onychodysplasia). Respiratory distress occurs frequently.

Because of the facial malformations and the abnormal and fragile teeth, the airway must be examined closely with regard to difficult management. Assessment of respiratory function (clinical examination, chest radiographs and/or computed tomography scanning, pulmonary function tests, arterial blood gas analysis) is required secondary to the usually narrow thorax, which results in decreased compliance and respiratory distress in early infancy. Cor pulmonale has not been described in this condition, but the potential for increased right ventricular pressure should be kept in mind.

Patients may have difficult airway management and be at risk for postoperative respiratory distress in the presence of reduced pulmonary reserves. Maintain spontaneous ventilation until the airway has been secured. Care with positioning is essential because of joint laxity and the tendency for dislocations. Keep spinal and vertebral anomalies in mind if considering central neuraxial blockade. Abnormal clavicles may make central venous access difficult (more so for subclavian than for internal jugular vein approach).

Avoid neuromuscular blockers until the airway has been secured. Patients may have a reduced respiratory reserve if the thorax is significantly affected. Respiratory depressants should be used with care.

Yunis-Varon Syndrome: Autosomal recessive inherited syndrome associated with generalized skeletal dysplasia and other features such as cardiac anomalies (tetralogy of Fallot, cardiomyopathy) and severe neurologic impairment (profound developmental delay, agenesis of the corpus callosum, arrhinencephaly). Death in the neonatal period is frequent.

Pyknodysostosis: Inherited syndrome characterized by congenital osteosclerosis, short stature, frontal and occipital bossing, short wide hands, and multiple other anomalies.