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Velopharyngeal insufficiency: high detection rate of genetic abnormalities if associated with additional features
  1. Charlotte W Ockeloen1,
  2. Jennifer Simpson2,
  3. Jill Urquhart3,
  4. Julie Davies4,
  5. Melanie Bowden4,
  6. Kathryn Patrick4,
  7. Jonathan Dore3,
  8. Jill Clayton-Smith3
  1. 1Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands
  2. 2University of Manchester Medical School, Manchester, UK
  3. 3Manchester Centre For Genomic Medicine, St. Mary's Hospital, Manchester Academic Health Sciences Centre, Manchester, UK
  4. 4North West North Wales Isle of Man Cleft Network, Royal Manchester Children's Hospital, Manchester, UK
  1. Correspondence to Dr Charlotte W Ockeloen, Department of Human Genetics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands; charlotte.ockeloen{at}radboudumc.nl

Abstract

Objective To review the clinical and molecular-genetic characteristics of 34 children who were referred to the clinical genetics department with a presenting diagnosis of definite or suspected velopharyngeal insufficiency (VPI, defined as the inability to close off the nasal from the oral cavity during speech) or hyponasal/hypernasal speech. All the patients referred also had additional anomalies and did not therefore comprise the whole VPI population.

Methods Patients were clinically investigated by a clinical geneticist. Fluorescent in situ hybridisation for chromosome 22q11 deletion and/or array comparative genomic hybridisation (array CGH) analysis was performed in all cases. A literature review was performed using the Pubmed online database.

Results Microdeletions or microduplications were identified in half of the patients. Six patients (∼18% of total) carried a chromosome 22q11 microdeletion, one patient had a chromosome 22q11 microduplication, and four patients had microdeletions in other chromosomes that were considered likely to be associated with the phenotype. One patient had KBG syndrome. Thus, an underlying genetic abnormality was found in approximately one-third (35%) of our patients. An additional seven patients harboured copy number variations that were considered benign or of unknown significance.

Conclusions We present an overview of patients with VPI or hyponasal/hypernasal speech with additional anomalies and their clinical and genetic findings. In one-third of these patients, an underlying genetic abnormality was identified. This has important implications for family counselling and medical follow-up. Furthermore, we recommend array CGH testing in all patients with VPI and associated anomalies because of the high percentage of copy number variants identified in these patients.

  • Genetics
  • Velopharyngeal insufficiency
  • Syndrome

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