The male phenotype in osteopathia striata congenita with cranial sclerosis

Sarah K. Holman, Phil Daniel, Zandra A. Jenkins, Rachel L. Herron, Tim Morgan, Ravi Savarirayan, C. W. Chow, Axel Bohring, Annette Mosel, Didier Lacombe, Bernhard Steiner, Thomas Schmitt-Mechelke, Barbara Schroter, Annick Raas-Rothschild, Sixto Garcia Miñaur, Mary Porteous, Michael Parker, Oliver Quarrell, Dagmar Tapon, Valérie Cormier-DaireSahar Mansour, Ruth Nash, Laurence A. Bindoff, Torunn Fiskerstrand, Stephen P. Robertson

Research output: Contribution to journalArticlepeer-review


Osteopathia striata with cranial sclerosis (OSCS) is an X-linked disease caused by truncating mutations in WTX. Females exhibit sclerotic striations on the long bones, cranial sclerosis, and craniofacial dysmorphism. Males with OSCS have significant skeletal sclerosis, do not have striations but do display a more severe phenotype commonly associated with gross structural malformations, patterning defects, and significant pre- and postnatal lethality. The recent description of mutations in WTX underlying OSCS has led to the identification of a milder, survivable phenotype in males. Individuals with this presentation can have, in addition to skeletal sclerosis, Hirschsprung disease, joint contractures, cardiomyopathy, and neuromuscular anomalies. A diagnosis of OSCS should be considered in males with macrocephaly, skeletal sclerosis that is most marked in the cranium and the absence of metaphyseal striations. The observation of striations in males may be indicative of a WTX mutation in a mosaic state supporting the contention that this sign in females is indicative of the differential lyonization of cells in the osteoblastic lineage.

Original languageEnglish
Pages (from-to)2397-2408
Number of pages12
JournalAmerican Journal of Medical Genetics, Part A
Issue number10
StatePublished - Oct 2011
Externally publishedYes


  • Osteopathia striata with cranial sclerosis
  • Skeletal dysplasia
  • WTX


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