Velopharyngeal insufficiency: high detection rate of genetic abnormalities if associated with additional features

• Published in: Archives of disease in childhood Vol. 99; no. 1; pp. 52 - 57
• Main Authors: Ockeloen, Charlotte W, Simpson, Jennifer, Urquhart, Jill, Davies, Julie, Bowden, Melanie, Patrick, Kathryn, Dore, Jonathan, Clayton-Smith, Jill
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group 01-01-2014; BMJ Publishing Group Ltd; BMJ Publishing Group LTD
• Subjects: Attention deficit hyperactivity disorder; Autism; Autism Spectrum Disorders; Biological and medical sciences; Child; Chromosome Deletion; Chromosomes; Chromosomes, Human, Pair 22 - genetics; Comparative Genomic Hybridization; Complications and side effects; Congenital Impairments; Delayed Speech; Development and progression; Diagnostic tests; DNA Copy Number Variations; Female; General aspects; Genes; Genetic abnormalities; Genetic aspects; Genetics; Hospitals; Humans; In Situ Hybridization, Fluorescence; Language; Learning disabilities; Learning Problems; Literature reviews; Male; Medical sciences; Miscellaneous; Motor Development; Non tumoral diseases; Otorhinolaryngology. Stomatology; Patient outcomes; Patients; Prevention and actions; Public health. Hygiene; Public health. Hygiene-occupational medicine; Referral; Risk factors; Speech; Speech Disorders - etiology; Speech Therapy; Studies; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Velopharyngeal insufficiency; Velopharyngeal Insufficiency - complications; Velopharyngeal Insufficiency - genetics; Netherlands; Human; Pediatrics; Epidemiology; Communication disorder; Association; ENT disease; Genetics; Pharynx disease; Speech articulation disorder; Anomaly; Diagnosis; Detection; Child; Velopharyngeal insufficiency; Public health; Syndrome
• ISSN: 0003-9888; 1468-2044
• DOI: 10.1136/archdischild-2013-304484

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.