Craniotubular Hyperostoses

Diaphyseal dysplasia is a sclerosing bone dysplasia characterized by progressive hyperostosis primarily affecting the diaphyses of long bones and, rarely, the skull. 

This autosomal dominant disorder is caused by mutations in the TGFB1 gene, which lead to overly active transforming growth factor beta-1 (TGFβ-1), causing increased bone formation (1). The population prevalence is unknown, but > 300 cases have been reported worldwide.

Diaphyseal dysplasia manifests during mid-childhood with bone or muscle pain, weakness, and wasting, typically in the legs. These symptoms usually resolve by age 30 years. Because of hyperostosis of the skull, cranial nerve compression and elevated intracranial pressure occur occasionally. Some patients are severely disabled; others are virtually asymptomatic.

The diagnosis of diaphyseal dysplasia is suspected by the combination of muscular deficits and hyperostoses of the long bones and skull. Typically, plain radiographs are done. The predominant radiographic feature is marked thickening of the periosteal and medullary surfaces of the diaphyseal cortices of the long bones, but findings vary. Medullary canals and external bone contours are irregular. The extremities and axial skeleton usually are spared. Rarely, the skull is involved, with calvarial widening and basal sclerosis.

Glucocorticoids may help relieve bone pain and improve muscle strength (2).

Endosteal hyperostosis is a disorder characterized by excessive bone formation particularly affecting the skull, mandible, clavicles, ribs, and long bones.

This condition is part of the SOST gene–related sclerosing bone dysplasias (1) and is usually inherited in an autosomal recessive manner. SOST mutations that cause endosteal hyperostosis lead to a deficiency of the functional protein sclerostin, which reduces the protein's ability to inhibit bone formation and results in the excessive bone growth observed in affected people. The population prevalence is unknown, but the disorder has been reported in approximately 30 people, primarily in people with Dutch ancestry. In endosteal hyperostosis, genetic lesions seem to affect the normal function of osteoblasts.

Endosteal hyperostosis usually represents a milder phenotype of bony hyperostosis. Overgrowth and distortion of the mandible and brow become evident during mid-childhood. Subsequently, cranial nerves become entrapped, leading to facial palsy and deafness. Life span is not compromised, stature is normal, and bones are not fragile.

Skull radiographs show widening and sclerosis of the calvaria, cranial base, and mandible. Diaphyseal endosteum in the tubular bones is thickened.

Surgical decompression of entrapped nerves may be helpful.

Sclerosteosis is a disorder characterized by excessive bone formation, particularly affecting the skull and mandible, and is often associated with syndactyly of the second and third digits. 

This autosomal recessive disorder is caused by a mutation in the SOST gene, which codes for the protein sclerostin, and is part of the SOST gene–related sclerosing bone dysplasias (1). Approximately 100 cases of sclerosteosis have been reported. Sclerosteosis is most common among Afrikaners of South Africa.

Sclerosteosis usually represents a more severe phenotype of bony hyperostosis. Overgrowth and sclerosis of the skeleton, particularly of the skull, develop during early childhood. Height and weight are often excessive. Initial symptoms and signs of sclerosteosis may include deafness and facial palsy due to cranial nerve entrapment. Distortion of facies, apparent by age 10 years, eventually becomes severe. Cutaneous or bony syndactyly of the second and third digits distinguishes sclerosteosis from other forms of craniotubular hyperostoses.

Sclerosteosis (Head and Facial Features)

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The diagnosis of sclerosteosis is suspected by characteristic skeletal abnormalities, particularly when the patient also has syndactyly. Typically, plain radiographs are performed. Predominant skull radiograph features are gross widening and sclerosis of the calvaria and mandible. Vertebral bodies are spared, although their pedicles are dense. Pelvic bones are sclerotic but have normal contours. Long bones have sclerosed, hyperostotic cortices and undermodeled shafts. A diagnostic genetic test is available.

Sclerosteosis (Radiograph)

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Surgery to relieve intracranial pressure or to decompress entrapped nerves may help. Depending on phenotypic severity, surgical reduction of mandibular overgrowth, maintenance of appropriate dentition, and surgical correction of syndactyly may also be required (2).