IMPAD1 mutations in two Catel-Manzke like patients

Authors

  • Mathilde Nizon,

    1. Département de génétique, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Hôpital Necker-Enfants Malades, Paris, France
    Search for more papers by this author
  • Yasemin Alanay,

    1. Pediatric Genetics Unit, Hacettepe University, Ihsan Dogramaci Children's Hospital, Ankara, Turkey
    2. Pediatric Genetics, Department of Pediatrics, Acibadem University, School of Medicine, Istanbul, Turkey
    Search for more papers by this author
  • Beyhan Tuysuz,

    1. Division of Genetics, Department of Pediatrics, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey
    Search for more papers by this author
  • Pelin Ozlem Simsek Kiper,

    1. Pediatric Genetics Unit, Hacettepe University, Ihsan Dogramaci Children's Hospital, Ankara, Turkey
    Search for more papers by this author
  • David Geneviève,

    1. Department of Medical Genetics, CHRU Montpellier, Montpellier 1 University, Montpellier, France
    Search for more papers by this author
  • David Sillence,

    1. Department of Genetic Medicine, University of Sydney, New South Wales, Australia
    Search for more papers by this author
  • Celine Huber,

    1. Département de génétique, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Hôpital Necker-Enfants Malades, Paris, France
    Search for more papers by this author
  • Arnold Munnich,

    1. Département de génétique, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Hôpital Necker-Enfants Malades, Paris, France
    Search for more papers by this author
  • Prof. Valérie Cormier-Daire

    Corresponding author
    1. Département de génétique, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Hôpital Necker-Enfants Malades, Paris, France
    • Département de Génétique, INSERM U781, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France.
    Search for more papers by this author

  • The authors declare no conflict of interest.

  • How to Cite this Article: Nizon M, Alanay Y, Tuysuz B, Kiper POS, Geneviève D, Sillence D, Huber C, Munnich A, Cormier-Daire V. 2012. IMPAD1 mutations in two Catel–Manzke like patients. Am J Med Genet Part A. 158A:2183–2187.

Abstract

Catel–Manzke syndrome is characterized by hyperphalangism with bilateral deviation of the index fingers and micrognathia with or without cleft palate. Some atypical patients present with additional malformations. No molecular basis is yet available. Most patients have an unremarkable family history but autosomal recessive inheritance has been recently suggested in a consanguineous family with recurrence in sibs. Catel–Manzke syndrome has overlapping features with Desbuquois dysplasia type 1 due to CANT1 (calcium-activated nucleotidase 1) mutations and also with “chondrodysplasia with joint dislocations, gPAPP type” due to IMPAD1 (Inositol Monophosphatase Domain containing 1) mutations recently reported in four patients, all characterized by short stature, joint dislocations, brachydactyly and cleft palate. The aim of our study was to screen CANT1 and IMPAD1 in Catel–Manzke patients. Three patients were diagnosed as classical Catel–Manzke syndrome and two as Catel–Manzke like patients, based on the presence of additional features. We identified two homozygous loss-of-function IMPAD1 mutations in the two Catel–Manzke like patients (p.Arg187X and p.Ser108ArgfsX48). The phenotype was characterized by severe growth retardation with short and abnormal extremities, cleft palate with micrognathia and knee hyperlaxity. Radiographs of hands and feet revealed numerous accessory bones with abnormally shaped phalanges and carpal synostosis. Based on this report, we concluded that IMPAD1 should be screened for patients with Catel–Manzke and additional features. © 2012 Wiley Periodicals, Inc.

Ancillary