Three patients with oculo‐auriculo‐vertebral spectrum and microdeletion 22q11.2

Abstract

We report on three unrelated patients with the 22q11.2 microdeletion syndrome (del22q11) who have phenotypic anomalies compatible with oculo-auriculo-vertebral spectrum (OAVS). Hemifacial microsomia, unilateral microtia, hearing loss, congenital heart/aortic arch arteries defects, and feeding difficulties were present in all three patients. Additional anomalies occasionally diagnosed included coloboma of the upper eyelid, microphthalmia, cerebral malformation, palatal anomalies, neonatal hypocalcemia, developmental delay, and laryngomalacia. Several clinical features characteristic of OAVS have been described in patients with del22q11 from the literature, including ear anomalies, hearing loss, cervical vertebral malformations, conotruncal cardiac defects, renal malformations, feeding and respiratory difficulties. Atretic ear with facial asymmetry has been previously described in one patient. Thus, clinical expression of hemifacial microsomia and microtia resembling OAVS should now be included within the wide phenotypic expression of del22q11. The occurrence of this manifestation in del22q11 is currently low. Nevertheless, patients with hemifacial microsomia and microtia associated with clinical features typically associated with del22q11 should now have for specific cytogenetic testing.

Atypical 581-kb 22q11.21 Deletion in a Patient with Oculo-Auriculo-Vertebral Spectrum Phenotype

“…However, several chromosomal rearrangements involving the 22q11.21 region have been found in patients with OAVS [Herman et al, 1988;Pridjian et al, 1995;Hathout et al, 1998;Derbent et al, 2003;Jackson et al, 2007;Xu et al, 2008;Digilio et al, 2009;Lafay-Cousin et al, 2009;Rosa et al, 2010;Tan et al, 2011;Quintero-Rivera and Martinez-Agosto, 2013;Torti et al, 2013;dos Santos et al, 2014;Beleza-Meireles et al, 2015], pointing to this region as a genomic candidate locus for the syndrome.…”

“…Several chromosomal abnormalities have also been found in association with OAVS, suggesting different chromosomal candidate regions [Rooryck et al, 2010;Brun et al, 2012;Ballesta-Martínez et al, 2013;BelezaMeireles et al, 2014]. However, chromosome 22 anomalies have been most frequently reported in patients with OAVS, particularly distal 22q deletions [Herman et al, 1988;Kobrynski et al, 1993;Balci et al, 2006;Xu et al, 2008;Digilio et al, 2009;Tan et al, 2011;Quintero-Rivera and Martinez-Agosto, 2013;Torti et al, 2013;dos Santos et al, 2014;Beleza-Meireles et al, 2015].…”

Copy number variations in 375 patients with oesophageal atresia and/or tracheoesophageal fistula

“…9,10 In addition to their well-established role in the development of congenital anatomical malformations in general, 11 CNVs contribute to disease aetiology in several genetic syndromes. These include those having OA/TOF as part of their phenotypic spectrum such as Feingold syndrome, 12 22q11 deletion syndrome, 13 CHARGE syndrome 14 and mandibulofacial dysostosis. 15 Furthermore, de novo disease-causing CNVs have been described in patients with non-syndromic OA/TOF and the VACTERL association.…”

Genome-Wide Scanning Reveals Complex Etiology of Oculo-Auriculo-Vertebral Spectrum

“…In addition, a few patients showing clinical overlap with OAVS had mutations in sal-like 1 (SALL1) (Kohlhase et al 1999;Keegan et al 2001;Kosaki et al 2007) or Treacher Collins-Franceschetti syndrome 1 (TCOF1) (Su et al 2007), the genes responsible for most cases of Townes-Brocks syndrome [OMIM 107480] and Treacher Collins syndrome [OMIM 154500], respectively, which are also associated with first and second branchial arch anomalies. Even though cytogenetic alterations have been associated with many cases of OAVS, most of the chromosomal aberrations are patient-specific, except that chromosome 5p (Choong et al 2003;Descartes 2006;Josifova et al 2004;Ala-Mello et al 2008) and 22q (Balci et al 2006;Xu et al 2008;Derbent et al 2003;Digilio et al 2009) have been implicated in a number of cases.…”