Chromosome 22q11.2 deletion and phenotypic features in 30 patients with conotruncal heart defects

Abstract

This report describes the dysmorphic features and frequency of 22q11.2 deletion (del22q11) in 30 Turkish patients with conotruncal heart defects (CTHDs). Fluorescence in situ hybridization (FISH) analysis revealed deletions in the 22q11.2 region in nine (30%) individuals. The CTHDs in this group were tetralogy of Fallot (four cases), double-outlet right ventricle (DORV) (two cases), transposition of great arteries (two cases), and ventricular septal defect (VSD) associated with other CTHDs (one case). The frequency of del22q11 in the study group was relatively high because many of the patients with dysmorphic findings also had cardiac anomalies involving the pulmonary artery, ductus arteriosus, or the aortic arch and its main branches. Twenty of the 30 patients exhibited several dysmorphic findings. Two of the nine patients with del22q11 exhibited no apparent dysmorphic features other than sacral dimple. Interestingly, one of the patients with del22q11 had a phenotypic appearance similar to that seen in oculo-auriculo-vertebral spectrum (OAVS). This individual had left microtia, atresia of the external meatus, mandibular asymmetry, and peripheral facial nerve paralysis. His mental development was normal and there were no abnormalities on ophthalmological examination. The CTHDs in this patient were situs inversus dextrocardia, DORV, pulmonary stenosis, and VSD. Radiographs of this patient showed platybasia, complete fusion of C2-C3, and posterior fusion of the T1-T2 vertebrae. This particular case indicates that the phenotypic features of del22q11 and OAVS may overlap.

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.…”

Microsomía hemifacial. Revisión de la literatura

“…15 Dentro de las causas genéticas, si bien la mayoría de los casos son esporádicos, en algunos casos se ha observado un componente genético autosómico dominante (asociado al cromosoma 14), 16,17 un componente autosómico recesivo 18 y alteraciones cromosómicas, principalmente en los cromosomas 5 (deleción de 5p), 18 (trisomía) y 22 (deleción de 22q11.2), entre otros. 19,20 Other authors suggest this relationship between lack of migration of cells of the neural crest and HFM because in the absence of these cells there is less vascular endothelial growth factor (VEGF). This growth factor promotes the proliferation of Meckel cartilage, and the absence of VEGF creates a correlation with mandibular hypoplasia.…”

“…15 Within the genetic causes, even though most cases are sporadic, in some cases there has been an autosomal dominant genetic component (associated with chromosome 14), 16,17 an autosomal recessive component, 18 and chromosomal alterations, mainly in chromosomes 5 (5p deletion), 18 (trisomy) and 22 (22q11.2 deletion), among others. 19,20 …”

Dysplastic changes in the peripheral blood of children with microdeletion 22q11.2

“…Approximately 75% of patients with this microdeletion have congenital heart disease (CHD), with conotruncal anomalies and cardiac outflow tract defects being most frequent forms. Clinical studies have revealed that almost all patients with the combination of del22q11.2 and CHD also exhibit one or more phenotypic features of DGS/VCFS, as well as other extracardiac malformations [1][2][3]. A recent study in mice demonstrated 25 genes in the deleted region; however, the role and functions of the genes in the deleted region are not fully understood [4].…”