Atypical microdeletion 22q11.2 in a patient with tetralogy of Fallot

Abstract

The 22q11.2 microdeletion syndrome (22q11.2 DGS) is characterized by an extreme intrafamilial and interfamilial variability. The main clinical features are congenital heart defects, palatal abnormalities, learning disability, facial dysmorphisms and immune deficiency. In 85-90% of cases, the 22q11.2 DGS is caused by a heterozygous *3-Mb deletion, including the TBX1 gene, considered one of the major genes responsible for heart defects. Individuals with atypical deletions with at least one breakpoint outside low copy repeats have been reported. Our patient is a child presenting tetralogy of Fallot (TOF) with an atypical 22q11.2 deletion proximal to the critical DiGeorge region. The rearrangement was inherited from the healthy mother and spanned *642-970 kb, encompassing DGCR6 and PRODH, two novel possible candidate genes for conotruncal heart defects.

Different Types of Deletions Created by Low-Copy Repeats Sequences Location in 22q11.2 Deletion Syndrome: Genotype–Phenotype Correlation

“…Usually they include congenital heart defect (conotruncal malformations), developmental delay/intellectual disability (DD/ID), behavioral disorders, palatal abnormalities (velopharyngeal incompetence, cleft palate and bifid uvula), characteristic face, hypocalcemia and immune deficiency. Most proximal deletions are de novo [ 5 , 16 , 17 ].…”

“…The main candidate gene for heart defects is TBX1 located in the LCR A–B interval [ 33 ]. Other genes in this region that were considered as contributing to the development of cardiac anomalies were: PRODH , DGCR6 and DGCR8 [ 16 , 34 ]. In a large study of congenital heart defects in 22q11.2DS, comprising 1053 cases, it is suggested that although the LCR A–B region was considered the critical region for the 22q11.2 phenotype and especially for heart defects, the presence of congenital cardiac defects in patients with LCR B–D and LCR C–D deletions (20–30% of cases) highlights the importance of the LCR C–D region in normal cardiac development, and proposes haploinsufficiency of the CRKL gene as the main factor involved in conotruncal heart defects [ 35 ].…”

Prenatal phenotype of 22q11 micro-duplications: A systematic review and report on 12 new cases

“…Cardiovascular malformations were a prominent anomaly among the foetuses we reported (40%), including atrial and/or ventricular septal defects, Fallot tetralogy and valvular anomalies. Many genes have been suspected to be responsible for the CHD observed among 22q11.2 CNV carriers (CRKL, TBX1, MAPK1, HIRA, CECR1, DGCR6, DGCR8, HIC2 and PRODH, (Carli et al 2021;Morrow et al 2018)) and HIRA, TBX1 and CECR1 were incriminated among CHD patients who were carriers of 22q11 duplications of various sizes in both the prenatal and postnatal periods (Carli et al 2021). Except for CECR1 and MAPK1, all of these genes are located in the typical 22q11.2 interval.…”

SOSPCNN: Structurally Optimized Stochastic Pooling Convolutional Neural Network for Tetralogy of Fallot Recognition

“…Tetralogy of Fallot (TOF) is a congenital defect that influences normal blood flow through the heart [1]. It is made up of 4 defects of the heart and its blood vessels [2]: (a) ventricular septal defect, (b) overriding aorta, (c) right ventricular outflow tract stenosis, and (d) right ventricular hypertrophy.…”