Craniodiaphyseal dysplasia, autosomal dominant (CDD)

(OMIM phenotype number #122860)

Craniodiaphyseal dysplasia is a severe form of bone dysplasia, characterized by massive generalised hyperostosis and sclerosis, primarly involving the facial bones and the skull, leading to severe deformity. Patients with CDD have facial abnormalities in early infancy. During childhood, progressive bony encroachment upon cranial foramina leads to severe neurological impairment. The bone deposition results in progressive stenosis of craniofacial foramina and facial distortion (leonine facies). In particular, infants affected by CDD may have respiratory difficulty owing to nasal obstruction before the characteristic facial appearance has developed. It has been observed heterozygous mutations located in the secretion signal of the SOST gene in two CDD patients and demonstrated that these SOST mutations prevent sclerostin secretion resulting in increased bone formation.

Gene

SOST gene, 17q21.31 (OMIM gene/locus number #605740) (see also VBD)

Phenotype

Leonine facies, increased bone mineral density, hyperostosis, osteosclerosis, obliteration of the sinuses, middle ear cavities, internal acoustic canals, and optic nerve canals, progressive hearing loss, progressive visual loss (cranial nerve compression, especially of II and VIII), cortical sclerosis of facial bones, macrocephaly, prominent mandible, facial diplegia, strabismus, exophthalmus, hypertelorism, papilledema, saddle nose, broad flat nasal bridge, choanal stenosis, increased intracranial pressure, headaches, seizures, mental retardation (however, in the majority of cases developmental progress was normal until hindered by progressive deterioration in vision and hearing), diaphyseal sclerosis, thickened and sclerotic ribs, undertubulation of the long bones of the legs, short stature (growth may be markedly retarded and delayed sexual maturation has been reported), difficulty breathing through the nostrils, and respiratory obstruction.
 

Images

a b
c d

Fig. a,b,c,d. Radiological findings of a case with CDD at the age of 3 years. There are marked thickening and sclerosis of the skull and whole facial bones. The ribs are also thickened and sclerotic. Mild undertubulation of the long bones of leg is noted.

Reproduced from H Genet, Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia, 2011;129:497-502, Kim SJ, Bieganski T, Sohn YB, Kozlowski K, et al., with permission of Springer.


References

  1. Brueton LA, Winter RM. Craniodiaphyseal dysplasia. J Med Genet. 1990 Nov;27(11):701-6.
  2. Kim SJ, Bieganski T, Sohn YB, Kozlowski K, et al. Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia. Hum Genet. 2011 May;129(5):497-502.
  3. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Nov;26(11):2717-8.
  4. http://www.omim.org