A 2.84 Mb deletion at 21q22.11 in a patient clinically diagnosed with marden–walker syndrome

Authors

  • María Carmen Carrascosa-Romero,

    Corresponding author
    • Neurología Neonatal. Servicio de Pediatría, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
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  • Javier Suela,

    1. NIMGenetics (New Integrated Medical Genetics), Madrid, Spain
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  • José Manuel Pardal-Fernández,

    1. Neurofisiología. Servicio de Pediatría, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
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  • Eva Bermejo-Sánchez,

    1. Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain
    2. Spanish Collaborative Study of Congenital Malformations (ECEMC), CIAC (Research Center on Congenital Anomalies), Instituto de Salud Carlos III, Madrid, Spain
    3. CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain
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  • Alberto Vidal-Company,

    1. Nefrología pediátrica. Servicio de Pediatría, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
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  • Alexandra MacDonald,

    1. Spanish Collaborative Study of Congenital Malformations (ECEMC), CIAC (Research Center on Congenital Anomalies), Instituto de Salud Carlos III, Madrid, Spain
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  • Roque Tébar-Gil,

    1. Jefe del Servicio de Pediatría, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
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    • deseased.
  • María Luisa Martínez-Fernández,

    1. Spanish Collaborative Study of Congenital Malformations (ECEMC), CIAC (Research Center on Congenital Anomalies), Instituto de Salud Carlos III, Madrid, Spain
    2. CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain
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  • María Luisa Martínez-Frías

    1. Spanish Collaborative Study of Congenital Malformations (ECEMC), CIAC (Research Center on Congenital Anomalies), Instituto de Salud Carlos III, Madrid, Spain
    2. CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain
    3. Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid. Ministerio de Educación, Cultura y Deporte, Madrid, Spain
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  • The authors declare no conflict of interest.

Pediatría. Complejo Hospitalario Universitario de Albacete, Hermanos Falcó 37., Albacete 02006, Spain.

Facultad de Medicina, Director Centro de Investigación Anomalías Congénitas (CIAC), Instituto de Salud Carlos III, Avda. Monforte de Lemos, 5. Pabellón 3-1ª planta, Madrid 28029, Spain.

Abstract

We present a girl with the characteristic clinical picture associated with Marden–Walker syndrome (MWS; OMIM 248700), including mask-like face with blepharophimosis, joint contractures, intellectual disability, a multicystic dysplastic kidney and cerebral dysgenesis. The long-term follow-up allowed us to monitor the evolution of the phenotype in this patient, and among the main findings we highlight the following: demyelination of the pyramidal tract demonstrated by transcranial magnetic stimulation and the involvement of the levator muscles of angle of mouth in fixed facial expression with relative integrity of the rest of the facial expression muscles. A 244 k array comparative genomic hybridization (aCGH) was carried out and showed a de novo interstitial deletion of approximately 2.84 Mb affecting only the cytoband 21q22.11 (genome coordinates chr21:31,874,016–34,711,763). We selected 10 of the most recent published cases with either total or partial deletions of cytoband 21q22.11 that provided good characterization of the genomic size or the genes in the deleted regions. We observed that in nine of the 10 cases the deleted regions included the RUNX1 gene in 21q22.12, which is not affected in the current patient's deletion or in that of Patient 3 from Roberson et al. [2011]. After a comparison of shared deleted genes between cases, and correlation of their potential phenotypes, we concluded that the pattern of defects considered for a diagnosis of MWS may represent part of the phenotypic expression of a partial or total deletion of 21q22.11. © 2013 Wiley Periodicals, Inc.

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