Distal 13q deletion syndrome in a fetus with esophageal atresia

Chromosome 13

Previous literature has categorized 3 groups of the 13q deletion syndromes: 1) proximal deletions not extending into q32, 2) more distal deletions including at least of part of q32, 3) most distal deletions involving q33-34. Kotani et al. introduce a Japanese female infant with a prenatal diagnosis of 13q deletion syndrome, who had the following clinical manifestations—fetal growth restriction, right microphthalmia, left coloboma, Dandy-Walker malformation (DWM), overlapping fingers, ventral ectopia of the anus, hearing loss, and finally an esophageal atresia without tracheoesophageal fistula. At 48 days old she underwent surgery for her esophageal defect and was later discharged at 7 months old. Microarray analysis revealed a 22.12 Mb deletion at 13q31.3-qter, which is consistent with the most severe form of group 2 deletions. Genes in this genomic region include (among others) GPC5/GPC6, ZIC2/ZIC5, EFBN2, IRS2, COLA1, and COLA2. Haploinsufficiency of ZIC2/ZIC5 is associated with the seen DWN phenotype; haploinsufficiency of EFBN2 is associated with the seen eye malformation and hearing loss. Genes IRS2, COLA1, and COLA2 are also suggested to have a pathological effect on eye development to yield clinical manifestations such as the patient’s right microphthalmia. However, the authors found that the esophageal atresia without fistula was not demonstrated in previously reported cases with 13q deletions, instead they only found two previous cases of 13q deletion with esophageal atresia with fistula. Holistically, the authors’ literature review and the current case all showed partial symptoms of vertebral defects (V), anorectal malformations (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L) (VATER/VACTERL). Interestingly, the current patient did not show any cardiac defects. The authors suggest that there is an association between the rare phenotype of esophageal atresia with the deletion of the 13q31.3-qter region; such patients with both 13q deletion syndrome and esophageal atresia are then suggested to likely show other VATER/VACTERL manifestations. It is also possible that these symptoms are associated with EFBN2 haploinsufficiency. Further accumulation of cases is needed to better elucidate the range of phenotypes for 13q deletion syndrome.