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At a glance

A severe bone fragility disorder with frequent fractures that is associated with craniosynostosis, hydrocephalus, ocular proptosis, and dysmorphic facial features. Radiographs show osteogenesis imperfecta-like skeletal features.

Incidence

Five cases have been described (and two fetuses).

Genetic inheritance

Autosomal dominant inheritance, but de novo mutations have also been found. Cole-Carpenter Syndrome (CCS) 1 is caused by missense mutations in the P4HB (Procollagen-Proline, 2-Oxoglutarate-4-Dioxygenase, Beta Subunit) gene, which has been mapped to chromosome 17q25.3. Autosomal recessive inherited CCS 2 (described in one boy and two fetuses only) is caused by mutations in the SEC24D (SEC24-Homolog D) gene, which is located on chromosome 4q26. Other than prominent skull ossification defects that are absent in CCS 1, the two types are very similar.

Diagnosis

Based on the clinical and radiological findings. Molecular genetic testing is available.

Clinical aspects

These patients appear normal at birth, but multiple fractures of the long bones are noted soon thereafter, followed by extensive demineralization with recurrent diaphyseal fractures of the weight-bearing bones already before the first birthday. Short stature, progressive kyphoscoliosis, vertebral compression fractures, pectus excavatum, severe osteopenia, and deformation of the extremities and cystic bone changes may develop early. Similar to severe ☞Osteogenesis Imperfecta, radiographic examination of the distal femora may reveal “popcorn epiphyses,” referring to the x-ray-appearance of what seems to be disintegrated growth plates. Facial abnormalities may include facial structural asymmetry, craniosynostosis of the coronal and frontal sutures with rapidly progressive, communicating hydrocephalus, enlarged fontanelle with widening of coronal, sagittal, and lambdoid sutures and multiple wormian bones due to ossification defects (CCS 2), development of marked frontal and temporal bossing, dysplastic ears, downslanting palpebral fissures, hypertelorism, short mid-face, shallow orbits with ocular proptosis, blue sclerae, severe midface hypoplasia, micrognathia, and dental anomalies (small teeth with hypoplastic enamel). Normal neurologic development has been reported, but abnormal crying (high-pitched voice), and gait and generalized hypotonia are common. Hydrops fetalis has been described in one case. Serum levels of calcium, phosphorus, alkaline phosphatase, parathyroid hormone, free thyroxine, and free triiodothyronine are typically normal.

Precautions before anesthesia

Assess for signs of difficult airway management and increased intracranial pressure (ICP). Inquire about fractures and forces involved. Preoperative blood work should include a complete blood count and serum levels of electrolytes including calcium.

Anesthetic considerations

With the aforementioned craniofacial anomalies, airway management should be expected to be difficult, thus maintaining spontaneous ventilation is recommended until the airway has been secured. Alternative airway management options should be immediately available (eg, supraglottic airway device, fiberoptic bronchoscope) and adherence to an established difficult airway algorithm is advised. A surgeon familiar with surgical airway management and the necessary equipment should easily be available in the operating room. Alternatively, an awake (or asleep) fiberoptic intubation ...

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