title: Velopharyngeal insufficiency: high detection rate of genetic abnormalities if associated with additional features.
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.
authors.affiliation: Department of Human Genetics, Radboud university medical center, Nijmegen , The Netherlands.
authors.forename: Charlotte W
authors.initials: CW
authors.lastname: Ockeloen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Simpson
authors.forename: Jill
authors.initials: J
authors.lastname: Urquhart
authors.forename: Julie
authors.initials: J
authors.lastname: Davies
authors.forename: Melanie
authors.initials: M
authors.lastname: Bowden
authors.forename: Kathryn
authors.initials: K
authors.lastname: Patrick
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dore
authors.forename: Jill
authors.initials: J
authors.lastname: Clayton-Smith
mesh_terms: D002648:Child; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D013064:Speech Disorders / Q000209:etiology*; D014681:Velopharyngeal Insufficiency / Q000150:complications / Q000235:genetics*
keywords: Genetics; Syndrome; Velopharyngeal insufficiency