= Generalized cortical hyperostosis = Endosteal hyperostosis

= extremely uncommon homozygous disorder of intramembranous ossification part of craniotubular hyperostoses; may be related to hyperphosphatasemia

Classification:

1. Van Buchem disease (autosomal recessive)
   [Franciscus Stephanus Petrus (Frans) van Buchem (1897–1979), Dutch internist]
   • facial nerve palsy
2. Truswell-Hansen disease = sclerosteosis (autosomal recessive)
   • progressive facial nerve palsy
   • syndactyly of 2^nd + 3^rd digits with nail dysplasia, tall stature
3. Worth disease (autosomal dominant)
   • flattened forehead
   • elongated mandible, decreased gonial angle
4. Nakamura disease (autosomal dominant)
   • enlargement of mandible + maxilla with sparing of mandibular rami

Genetics: mutations in Wnt signaling pathway of osteoblasts on chromosome 17q12-q21 → inhibition of formation of a complex composed of 4 proteins (axin, adenomatous polyposis coli, glycogen synthase kinase 3, b-catenin) → proliferation and differentiation of osteoblasts → increased bone formation

• facial distortion; paralysis of facial nerve
• recurring headaches + dizziness ← reduced intracranial space + increased intracranial pressure
• auditory + ocular disturbances (in late teens ← foraminal encroachment)
• increased alkaline phosphatase (in 50%)

Location: skull, mandible, clavicles, ribs, long-bone diaphyses

• Long bones
  • symmetrical dense homogeneous endosteal cortical thickening of diaphyses of long bones
  • narrowed medullary canals
• Skull
  • thickening of skull, facial bones, mandible
  • obliteration of diploe
• Spine
  • increased density of the axial skeleton
  • spinous processes thickened + sclerotic

MR:

• herniation of cerebellar tonsils
• subtotal depletion of subarachnoid space
• distention of subarachnoid space along optic nerve sheaths

DDx:

1. Osteopetrosis (sclerosis of all bones, not confined to diaphyses)
2. Generalized hyperostosis with pachydermia (involves entire long bones, considerable pain, skin changes)
3. Hyperphosphatasia (infancy, widened bones but decreased cortical density)
4. Camurati-Engelmann disease (rarely generalized, involves lower limbs)
5. Pyle disease (does not involve middiaphyses)
6. Polyostotic fibrous dysplasia (rarely symmetrically generalized, paranasal sinuses abnormal, skull involvement)