Osteopathia striata with cranial sclerosis (OMIM ##300373) is an X-linked dominant sclerosing bone dysplasia that presents in females with macrocephaly, cleft palate, mild learning disabilities, sclerosis of the long bones and skull, and longitudinal striations visible on radiographs of the long bones, pelvis, and scapulae. In males this entity is usually associated with foetal or neonatal lethality, because of severe heart defects and/or gastrointestinal malformations, and is often accompanied by bilateral fibula aplasia. Recently, the disease-causing gene was identified as the WTX gene (FAM123B). Initially it was suggested that the mutations in the 5' region of the WTX gene are associated with male lethality. Mutation analysis in individuals of two families diagnosed with OSCS revealed two novel WTX mutations. In one family, the affected male is still alive in his teens. These mutations underline the unpredictability of male survival and suggest that WTX mutations should be considered in cases of male cranial sclerosis, even if striations are not present. An overview of all known mutations and their associated characteristics provide a valuable resource for the molecular analysis of OSCS.
© 2010 John Wiley & Sons A/S.