Incidence and significance of 22q11.2 hemizygosity in patients with interrupted aortic arch

Abstract

Interruption of the aortic arch (IAA) is a severe malformation of the heart with known association to DiGeorge syndrome (DGS) and 22q11.2 hemizygosity. The aim of this study was to establish incidence and significance of 22q11.2 hemizygosity in an unbiased sample of patients with IAA. All 15 children with IAA who were referred to our hospital in a 3-year period were tested by chromosome and fluorescence in situ hybridization (FISH) analysis with the probes D22S75, Tuplel, and cHKAD26 and by a set of 10 simple tandem repeat polymorphic (STRP) markers. In nine of 11 children with IAA type B, 22q11.2 hemizygosity was demonstrated by FISH and STRP analysis, but in none of the four children with type A. In all but one child, deletion size was approximately 3 Mb. The girl with the smaller deletion of approximately 1.5 Mb differed because of an Ullrich-Turner syndrome-like phenotype and severe T-cell defect. Additionally, in one patient with phenotypic signs of DGS, a small deletion distal to the known DGS region containing the marker D22S308 was suspected by STRP analysis. One deletion was shown to be inherited from a healthy father and one IAA type A recurred in a sib. T-cell anomalies were evident in eight of the nine children with classical deletion, five of whom suffered also from hypoparathyroidism. With respect to cause and clinical course, IAA type A and B were shown to represent different entities. This study showed that variable symptoms of 22q11.2 hemizygosity may cluster.

Anatomic patterns of conotruncal defects associated with deletion 22q11

“…[32][33][34][35][36][37][38] In children with IAA type A (after the left subclavian artery), deletion 22q11 was never observed in our series 32 but was occasionally reported by others. 36 When IAA type B is associated with deletion 22q11, the infundibular septum is commonly hypoplastic or absent and is deviated posteriorly and to the left; the VSD results in a subarterial position doubly committed with the pulmonary and aortic valves. 32,38 Ventricular septal defect (15 cases) Additional CVMs were detected also in patients with VSD and deletion 22q11.…”

Detailed analysis of 22q11.2 with a high density MLPA probe set

“…MLPA proved to be a relatively inexpensive assay with high sensitivity and specificity. However, there have been reports from several laboratories about variant deletions and duplications that are neither detected by chromosomal analysis with FISH using the N25 or TUPLE1/HIRA diagnostic probes nor the currently available MLPA kit for DGS/VCFS Rauch et al, 1998;O'Donnell et al, 1997;Kurahashi et al, 1997]. Therefore, in collaboration with MRC Holland we have developed a MLPA-HD kit for the 22q11 region.…”

A rare association of interrupted aortic arch type C and microdeletion 22q11.2

“…Some authors have recommended deletion screening of all patients with IAA, truncus arteriosus and tetralogy of Fallot [8], while others share the opinion that IAA type B is the only conotruncal defect that "per se" deserves screening for 22q11.2 deletion, independently from clinical phenotype [4,13]. On the other hand, it has been suggested that 22q11.2 deletion testing should be performed only in patients in which heart defects are associated with "classic" or "subtle" clinical anomalies falling within the phenotypic spectrum of 22q11.2 deletion [4].…”