Mosaic 18q21.2 deletions including the TCF4 gene: A clinical report

Authors

  • Massimiliano Rossi,

    Corresponding author
    1. Centre de référence des anomalies du développement, Service de Cytogénétique Constitutionnelle, Hospices Civils de Lyon, Bron, France
    • Centre de Référence des Anomalies du Développement, Service de Cytogénétique Constitutionnelle, Hospices Civils de Lyon, 59 boulevard Pinel, 69677, Bron Cedex, France.
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  • Audrey Labalme,

    1. Centre de référence des anomalies du développement, Service de Cytogénétique Constitutionnelle, Hospices Civils de Lyon, Bron, France
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  • Marie-Pierre Cordier,

    1. Centre de référence des anomalies du développement, Service de Cytogénétique Constitutionnelle, Hospices Civils de Lyon, Bron, France
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  • Marianne Till,

    1. Centre de référence des anomalies du développement, Service de Cytogénétique Constitutionnelle, Hospices Civils de Lyon, Bron, France
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  • Gaëlle Blanchard,

    1. Centre de référence national des déficiences intellectuelles de causes rares, Service de Neuropédiatrie, Hospices Civils de Lyon, Bron, France
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  • Remi Dubois,

    1. Service de Chirurgie Pédiatrique, Hospices Civils de Lyon, Bron, France
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  • Laurent Guibaud,

    1. Service d'Imagerie Pédiatrique et Foetale, Hospices Civils de Lyon, Bron, France
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  • Sophie Heissat,

    1. Service de Gastroentérologie, Hépatologie et Nutrition Pédiatrique, Hospices Civils de Lyon, Bron, France
    2. Université de Lyon 1, Villeurbanne, France
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  • Etienne Javouhey,

    1. Service de Réanimation Pédiatrique, Hospices Civils de Lyon, Bron, France
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  • Alain Lachaux,

    1. Service de Gastroentérologie, Hépatologie et Nutrition Pédiatrique, Hospices Civils de Lyon, Bron, France
    2. Université de Lyon 1, Villeurbanne, France
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  • Pierre-Yves Mure,

    1. Service de Chirurgie Pédiatrique, Hospices Civils de Lyon, Bron, France
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  • Dorothée Ville,

    1. Centre de référence national des déficiences intellectuelles de causes rares, Service de Neuropédiatrie, Hospices Civils de Lyon, Bron, France
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  • Patrick Edery,

    1. Centre de référence des anomalies du développement, Service de Cytogénétique Constitutionnelle, Hospices Civils de Lyon, Bron, France
    2. Université de Lyon 1, Villeurbanne, France
    3. INSERM, U1028; CNRS, UMR5292; TIGER Team, Lyon, France
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  • Damien Sanlaville

    1. Centre de référence des anomalies du développement, Service de Cytogénétique Constitutionnelle, Hospices Civils de Lyon, Bron, France
    2. Université de Lyon 1, Villeurbanne, France
    3. INSERM, U1028; CNRS, UMR5292; TIGER Team, Lyon, France
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  • How to Cite this Article: Rossi M, Labalme A, Cordier M-P, Till M, Blanchard G, Dubois R, Guibaud L, Heissat S, Javouhey E, Lachaux A, Mure P-Y, Ville D, Edery P, Sanlaville D. 2012. Mosaic 18q21.2 deletions including the TCF4 gene: A clinical report. Am J Med Genet Part A 158A: 3174–3181.

Abstract

Pitt–Hopkins syndrome (PTHS) is characterized by distinctive facial dysmorphism, profound intellectual disability, and the possible occurrence of epilepsy and breathing anomalies. It is caused by haploinsufficiency of the TCF4 gene. No significant difference in clinical severity has been reported to date between PTHS patients carrying 18q21 deletions including the TCF4 gene, and those harboring TCF4 point mutations, suggesting a lack of genotype/phenotype correlation. Moreover, the size of 18q21 deletions including the TCF4 gene does not appear to have a significant effect on the phenotypic severity, suggesting that TCF4 haploinsufficiency is the most important prognostic factor in 18q deletions. We describe two unrelated patients presenting with clinical features reminiscent of PTHS and carrying mosaic interstitial 18q21 deletions characterized by array comparative genomic hybridization. One of the patients presented the lowest level of mosaic 18q21 deletion reported to date (5–10%). Our report and a review of the literature show that the mosaic status does not appear to have a significant effect on the clinical severity of 18q21 deletions, which are associated with a poor neurological outcome, whereas a mosaic TCF4 point mutation can result in a significantly milder phenotype. Malformations of internal organs are currently considered to be rare in PTHS. The patients described here had visceral anomalies, suggesting that a full morphological assessment, including heart and abdominal ultrasound scans, should be performed systematically in PTHS patients. © 2012 Wiley Periodicals, Inc.

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