Osteopathia striata with cranial sclerosis owing to WTX gene defect

Bram Perdu, Fenna De Freitas, Suzanne Frints, Meyke Schouten, Connie Schrander-Stumpel, Mafalda Barbosa, Jorge Pinto-Basto, Margarida Reis-Lima, Marie-Christine De Vernejoul, Kristin Becker, Mary-Louise Freckmann, Kathlijn Keymolen, Eric Haan, Ravi Savarirayan, Rainer Koenig, Bernhard Zabel, Filip Vanhoenacker, Wim Van Hul

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    60 Citations (Scopus)


    Osteopathia striata with cranial sclerosis (OSCS) is an X-linked dominant condition marked by linear striations mainly affecting the metaphyseal region of the long bones and pelvis in combination with cranial sclerosis. Recently, the disease-causing gene was identified as the WTX gene (FAM123B), an inhibitor of WNT signaling. A correlation was suggested between the position of the mutation and male lethality. We performed genotype and phenotype studies using 18 patients from eight families with possible WTX gene defects and expanded the clinical spectrum of the affected females. All investigated families diagnosed with OSCS had WTX gene defects. One family had a WTX gene deletion; three of four point mutations were novel. The earlier reported WTX c.1072C>T was detected in four sporadic patients and appears to be a hotspot for mutations. Based on the nature of the mutation present in a surviving male patient, our data do not support the hypothesis raised by Jenkins et al. (2009) regarding a genotype-phenotype correlation for male lethality. The finding of a gene involved in WNT signaling as the cause of this sclerosing bone phenotype is not unexpected, but further functional studies are needed to explain the specific features. The WTX gene is mutated in different types of cancer, and it remains to be explained why osteopathia striata patients appear not to have an increased risk of cancer.

    Original languageEnglish
    Pages (from-to)82-90
    Number of pages9
    JournalJournal of Bone and Mineral Research
    Issue number1
    Publication statusPublished - Jan 2010


    • Genotype
    • Osteopathia striata with cranial sclerosis
    • Phenotype
    • WTX


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