22q11.2 microduplication syndrome with associated esophageal atresia/tracheo‐esophageal fistula and vascular ring

Abstract

Key Clinical MessageThis case report describes a patient with a 22q11.2 duplication. His features, which include VACTERL association with an esophageal atresia/tracheo‐esophageal fistula and a vascular ring, expand the previously described phenotype for this duplication.

22q11.2 Microduplication: An Enigmatic Genetic Disorder

“…The "second hit" theory suggested recently for concomitant chromosomal imbalances, such as microdeletions, additional duplications, missense mutations, and reciprocal translocation, may add to the severity of the cognitive disorders. 6,8,9 In our patient, a proximal duplication was detected but there were no other concomitant genotypic anomalies. It is possible that the phenotypic anomalies are totally unrelated to the microduplication, but this does bear some similarity to DG/VCFS spectrum.…”

“…[16][17][18][19][20][21] There are reports of variable cognitive deficits, which are generally mild. 1,2,6,8,9,22 This case illustrates the considerable challenges in interpreting copy number variations. A review of the phenotype of microduplications involving similar LCRs did not establish any clear genotype correlation.…”

“…In cases of congenital anomalies without a clear genetic diagnosis, there is an increasing use of whole genome sequencing, exome analysis, or microarray, as the standard screening, and many more of these duplications are likely to be detected and concomitant anomalies are also picked up. 6,8,9,26 However, this enigmatic genetic disorder with its diverse phenotypic presentations and variable expressivity still confounds many clinicians. It is, therefore, extremely important that the entire range and diverse presentations are captured and these reports will eventually delineate the full spectrum of the phenotype, so as to aid prospective parents in counseling and help in providing adequate prenatal care and support.…”

“…1 There are some reports of esophageal atresia and VACTERL association. [9][10][11] The other anomalies are quite varied and include ocular anomalies, microcephaly, cleft lip, thyroid hemiagenesis, and subtle dysmorphic facial features. 8,[12][13][14][15] In addition, an increasing number of recent studies have shown a higher incidence of autism spectrum and psychiatric disorders in those with this microduplication but, surprisingly, it has also been shown to provide some protection against schizophrenia.…”

DiGeorge syndrome chromosome region deletion and duplication: Prenatal genotype‐phenotype variability in fetal ultrasound and MRI

“…Particularly interesting, these case reports also involved the Hirschsprung disease and intestinal malrotation . Moreover, Nguyen et al published a case report of VACTERL association in a 22q11.2 microduplication syndrome with associated esophageal atresia/tracheo‐esophageal fistula and vascular ring and found a distal 22q11.23 microduplication, spanning a 1.41‐Mb (arr22q11.23(23,652,517–25,066,472)X3) . This is of special interest, as one of our cases with a 1.4 Mb duplication in the exact same region at 22q11.23 or arr (hg19)22q.11.23(23,834,850‐24,992,002)x3 presented with duodenal atresia, raising a novel genotype‐phenotype relation for duplication of SMARCB1 and fetal gastrointestinal tract malformations.…”