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At a glance

A bone disorder characterized by marked hyperostosis of the craniofacial bones and diaphyseal expansion of the tubular bones resulting in significant clinical complications.

Synonym

Schäfer-Stein-Oshman Syndrome.

Incidence

Approximately 20 cases have been described in the literature.

Genetic inheritance

Both autosomal dominant and recessive forms, but most cases are sporadic. In some cases the parents were consanguineous. In autosomal dominant inherited Craniodiaphyseal Dysplasia (CDD), the defect is caused by inactivating mutations in the SOST (Sclerostin) gene, which has been mapped to chromosome 17q21.31. Sclerostin is mainly expressed by osteocytes and seems to play a crucial role in the skeletal response to mechanical stress and the regulation of bone remodeling. Binding of sclerostin to the cell surface receptors on osteoblasts will lead to inhibition of osteoblastic bone formation. Pharmacological inhibition of sclerostin stimulates bone formation, reduces bone resorption, and results in increased bone mineral density. In fact, drugs with these properties are currently trialed for treatment of osteoporosis. Thus, the mutations in the SOST-gene most likely lead to uncontrolled/uninhibited osteoblastic activity and bone formation.

Diagnosis

Based on the clinical features and confirmed by the radiological findings.

Clinical aspects

The most distinctive features include short stature and massive and progressive thickening and sclerosis of the skull, maxilla, mandible, clavicles, and ribs. The head circumference is increased and gross mandibular hyperplasia relative to the maxilla with limited mouth opening from severely restricted temporomandibular joint mobility will be challenging for the anesthesia team. Osteosclerosis and hyperostosis of skull and facial bones are so severe that the term “leontiasis ossea” (craniofacial bony deformity with lion-like appearance) has been used to describe the facial appearance. Aside from the aforementioned anomalies, facial dysmorphism is further characterized by prominent zygomatic bones and osseous expansion of the facial center, exophthalmos, profound hypertelorism, strabismus, nystagmus, facial hyperostosis resulting in overgrown nasal bridge, small upturned tip of the nose, abnormal dentition, facial nerve palsy, and facial muscle atrophy and weakness. Along the skull base, the bone depositions cause progressive stenosis of the craniofacial foramina and lead to cranial neuropathies with progressive deterioration of vision (nonreactive pupils and papilledema have been described) and hearing (eventually ending in blindness and deafness, respectively), obstruction of jugular venous outflow, chronic epiphora secondary to nasolacrimal duct obstruction, chronic nasal obstruction secondary to choanal stenosis (that may lead to respiratory distress in infancy), and obliteration of the diploic spaces, the middle ear cavities, and the paranasal sinuses. Other significant findings may include progressive hydrocephalus with increased intracranial pressure (ICP), episodic early morning or chronic headaches and herniation of the cerebellar tonsils through a small foramen magnum (brainstem compression), cervical syringomyelia, and restricted cervical spine (especially atlantoaxial) mobility. Flexion of the neck may be further limited by the bulky mandible pressing against the chest, ...

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