Nine new twin pairs with esophageal atresia: A review of the literature and performance of a twin study of the disorder

Abstract

The observation of higher concordance rates for MZ compared to DZ twin pairs indicates that genetic factors contribute to isolated EA.

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

“…One de novo CNV (16p13.3 duplication, see Table 1) overlapped two inherited 16p13.3 duplications (see Table 3). We classified the rare CNVs as benign (45), uncertain -likely benign (106) and uncertain (7). Interestingly, we could classify nine CNVs as uncertain-likely pathogenic and two as pathogenic.…”

“…4,5 A confirmed genetic syndrome or a chromosomal anomalyincluding aneuploidies as trisomy 13, 18 and 21 -can be identified in 6-10% of patients, 6 and there is a strong suspicion that genetic factors are involved in the remainder. A genetic background is further suggested by reports of families with multiple affected individuals, higher concordance rates in monozygotic twins compared with dizygotic twins, 7 higher recurrence risk for siblings and children of affected individuals and OA/TOF as a component features in numerous known chromosomal aberrations and monogenic syndromes. 8 Reports describing disease-causing copy number variations (CNVs) in patients with OA/TOF are rare.…”

Respiratory Care of Infants and Children with Congenital Tracheo-Oesophageal Fistula and Oesophageal Atresia

“…Other contributing factors, including environmental exposures, may also be important. 12 Studies of mouse and rat models and also tissue from humans with OA/TOF have implicated a defect in the Sonic Hedgehog ( Shh ) signalling pathway and its downstream effectors (including FOXf1 ), which contribute to epithelial/mesenchymal signalling. 13 Recently, a microdeletion that encompasses the FOX transcription gene cluster at 16q24.1, which affects foregut and lung development, has been implicated, 13 and other genes specific to defined genetic syndromes have also been identified.…”

“…12,27 Survival rates are lower in patients with multiple congenital anomalies, especially those with trisomies, who often have multiple major comorbidities. Treatment consists of TOF ligation.…”

Isolated esophageal atresia in both premature twins

“…It is known from the literature that the risk of esophageal atresia in such pregnancies is 2-3 times higher [6]. In the group of patients with isolated EA and birth weight >1500 g the survival rate is almost 100%.…”