Clinical and mutational spectrum of Mowat-Wilson Syndrome

Christiane Zweier, Christian T. Thiel, Andreas Dufke, Yanick J. Crow, Peter Meinecke, Mohnish Suri, Sirpa Ala-Mello, Frits Beemer, Sergio Bernasconi, Paolo Bianchi, Andrea Bier, Koen Devriendt, Boyan Dimitrov, Helen Firth, Renata C. Gallagher, Livia Garavelli, Gabriele Gillessen-Kaesbach, Louanne Hudgins, Helena Kääriäinen, Susan KarstensIan Krantz, Anca Mannhardt, Livija Medne, Jürgen Mücke, Maria Kibaek, Lotte Nylandsted Krogh, Maarit Peippo, Olaf Rittinger, Solveig Schulz, Susan L. Schelley, I. Karen Temple, Nick R. Dennis, Marjo S. Van Der Knaap, Patricia Wheeler, Baruch Yerushalmi, Martin Zenker, Heide Seidel, A. Lachmeijer, Trine Prescott, Cornelia Kraus, R. Brian Lowry, Anita Rauch

    Research output: Contribution to journalArticlepeer-review


    Mowat-Wilson Syndrome is a recently delineated mental retardation syndrome usually associated with multiple malformations and a recognizable facial phenotype caused by defects of the transcriptional repressor ZFHX1B. To address the question of clinical and mutational variability, we analysed a large number of patients with suspected Mowat-Wilson Syndrome (MWS). Without prior knowledge of their mutational status, 70 patients were classified into "typical MWS", "ambiguous" and "atypical" groups according to their facial phenotype. Using FISH, qPCR and sequencing, ZFHX1B deletions, splice site or truncating mutations were detected in all 28 patients classified as typical MWS. No ZFHX1B defect was apparent in the remaining 15 cases with ambiguous facial features or in the 27 atypical patients. Genotype-phenotype analysis confirmed that ZFHX1B deletions and stop mutations result in a recognizable facial dysmorphism with associated severe mental retardation and variable malformations such as Hirschsprung disease and congenital heart defects. Our findings indicate that structural eye anomalies such as microphthalmia should be considered as part of the MWS spectrum. We also show that agenesis of the corpus callosum and urogenital anomalies (especially hypospadias) are significant positive predictors of a ZFHX1B defect. Based on our observation of affected siblings and the number of MWS cases previously reported, we suggest a recurrence risk of around 1%. The lack of missense mutations in MWS and MWS-like patients suggests there may be other, as yet unrecognized phenotypes, associated with missense mutations of this transcription factor. © 2005 Elsevier SAS. All rights reserved.
    Original languageEnglish
    Pages (from-to)97-111
    Number of pages14
    JournalEuropean journal of medical genetics
    Issue number2
    Publication statusPublished - Apr 2005


    • Corpus callosum
    • HSCR
    • Hypospadias
    • Mental retardation
    • Microphthalmia
    • Mowat-Wilson
    • Parental mosaicism
    • ZFHX1B


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