Table 3.

Other Craniotubular Hyperostoses to Consider in the Differential Diagnosis of SOST-Related Sclerosing Bone Dysplasias

GeneDisorderMOIFeatures of Disorder
Overlapping w/SOST-related sclerosing bone dysplasiasDistinguishing from SOST-related sclerosing bone dysplasias
LRP4 LRP4-related sclerosteosis (OMIM 614305)AD
AR
  • Hyperostosis of long bones & skull
  • Facial deformity
  • Cranial nerve impingement & hearing loss
  • Tall stature
Normal or ↑ serum sclerostin concentration
LRP5 Endosteal hyperostosis, Worth type (OMIM 144750)AD
  • Hyperostosis of long bones & skull
  • Cranial nerve impingement & hearing loss
  • Enlargement of mandible
  • Smooth or bony swellings of palate (taurus palatinum)
  • Milder phenotype
  • Normal height
  • No syndactyly
SOST 1SOST-related craniodiaphyseal dysplasiaAD
  • Hyperostosis of skull
  • Facial deformity w/hypertelorism
  • Cranial nerve impingement & hearing loss
  • Severe progressive sclerosing bone dysplasia w/maximal involvement of craniofacial skeleton
  • Long bones, ribs, & pelvis less affected
  • Short stature
  • No syndactyly
SP7 2SP7-related craniodiaphyseal dysplasiaAR
  • Facial dysmorphism
  • Severe hyperostosis of calvarium, skull base, & mandible
  • Short stature & lean body habitus
  • Broad clavicles & ribs, scoliosis, & diaphyseal expansion of long bones
  • 1 of 2 persons reported had recurrent fractures.
TGFB1 3TGFB1-related Camurati-Engelmann diaphyseal dysplasia (See Camurati-Engelmann Disease.)AD
  • Hyperostosis of long bones
  • Frontal bossing, enlargement of mandible, proptosis, & cranial nerve impingement later in life in those w/severe disease
  • Proximal muscle weakness
  • Severe limb pain
  • Joint contractures
  • No syndactyly

AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance

1.

Craniodiaphyseal dysplasia is possibly heterogeneous. Heterozygous pathogenic variants in SOST have been demonstrated in two unrelated affected children [Kim et al 2011] (see Genetically Related Disorders).

2.
3.

Diagnosis of Camurati-Engelmann disease (CED) is established in a proband with the characteristic radiographic findings or (if radiographic findings are inconclusive) a heterozygous pathogenic variant in TGFB1 identified by molecular genetic testing.

From: SOST-Related Sclerosing Bone Dysplasias

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