Comprehensive genetic analysis of OEIS complex reveals no evidence for a recurrent microdeletion or duplication

Abstract

Omphalocele-exstrophy of the bladder-imperforate anus-spinal defects (OEIS) complex, or cloacal exstrophy (EC), is a rare constellation of malformations in humans involving the urogenital, gastrointestinal, and skeletal systems, and less commonly the central nervous system. Although OEIS complex is well-recognized in the clinical setting, there remains a significant lack of understanding of this condition at both the developmental and the genetic level. While most cases are sporadic, familial cases have been reported, suggesting that one or more specific genes may play a significant role in this condition. Several developmental mechanisms have been proposed to explain the etiology of OEIS complex, and it is generally considered to be a defect early in caudal mesoderm development and ventral body wall closure. The goal of this study was to identify genetic aberrations in 13 patients with OEIS/EC using a combination of candidate gene analysis and microarray studies. Analysis of 14 candidate genes in combination with either high resolution SNP or oligonucleotide microarray did not reveal any disease-causing mutations, although novel variants were identified in five patients. To our knowledge, this is the most comprehensive genetic analysis of patients with OEIS complex to date. We conclude that OEIS is a complex disorder from an etiological perspective, likely involving a combination of genetic and environmental predispositions. Based on our data, OEIS complex is unlikely to be caused by a recurrent chromosomal aberration.

Penile duplication as genital abnormality in OEIS complex

“…Although case reports for chromosomal abnormalities exist in literature, a microarray based study failed to identify any disease causing mutation in 14 candidate genes (Vlangos, 2011). The authors concluded that OEIS is unlikely to be caused by chromosomal abnormality and is most likely a complex disorder.…”

Misdiagnosis of a cloacal exstrophy variant as urorectal septum malformation in a fetus by ultrasound: A case report

“…The occurrence rate of cloacal exstrophy variants is approximately 1/200,000-1/400,000 (2). No single environmental factor or genetic defect in the etiology of cloacal exstrophy has been identified (3,4). Many affected pregnancies are terminated, while those that reach full term typically result in infant mortality shortly after delivery (5,6).…”

Prenatal findings of omphalocele–exstrophy of the bladder–imperforate anus–spinal defects (OEIS) complex

“…The complex is estimated to occur in 1 of 200 000-400 000 pregnancies. Recent findings suggest that OEIS is a complex disorder from an etiological perspective, likely involving a combination of genetic and environmental predispositions (Vlangos et al 2010). Prenatal counseling of families with a diagnosis of OEIS complex is challenging (Tiblad et al 2008;Wax et al 2009).…”