title: A 2.84 Mb deletion at 21q22.11 in a patient clinically diagnosed with Marden-Walker syndrome.
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.
authors.affiliation: Neurología Neonatal, Servicio de Pediatría, Complejo Hospitalario Universitario de Albacete, Albacete, Spain. mccarrascosa@sescam.jccm.es
authors.forename: María Carmen
authors.initials: MC
authors.lastname: Carrascosa-Romero
authors.forename: Javier
authors.initials: J
authors.lastname: Suela
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Pardal-Fernández
authors.forename: Eva
authors.initials: E
authors.lastname: Bermejo-Sánchez
authors.forename: Alberto
authors.initials: A
authors.lastname: Vidal-Company
authors.forename: Alexandra
authors.initials: A
authors.lastname: MacDonald
authors.forename: Roque
authors.initials: R
authors.lastname: Tébar-Gil
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Martínez-Fernández
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Martínez-Frías
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D054119:Arachnodactyly / Q000175:diagnosis / Q000235:genetics*; D016569:Blepharophimosis / Q000175:diagnosis / Q000235:genetics*; D001921:Brain / Q000473:pathology; D002648:Child; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D055028:Comparative Genomic Hybridization; D003240:Connective Tissue Diseases / Q000175:diagnosis / Q000235:genetics*; D003286:Contracture / Q000175:diagnosis / Q000235:genetics*; D019066:Facies; D005260:Female; D006801:Humans; D010641:Phenotype
keywords: Chromosome 21, intellectual disability; array-CGH, Marden-Walker syndrome; arthrogryposis multiplex congenita; microdeletion 21q22.11