A review of genetic factors underlying craniorachischisis and omphalocele: Inspired by a unique trisomy 18 case.

Abstract

Very few cases of craniorachischisis (CRN) with concomitant omphalocele (OMP) in the setting of trisomy 18 are reported in literature. Solitary midline closure defects are estimated to be more prevalent in trisomy 18 compared to the general population. Neurulation defect comparisons include anencephaly 0-2% versus 0.0206%, spina bifida 1-3% versus 0.0350%, and encephalocele 0-2% versus 0.0082% [Parker et al. (2010); Birth Defects Research. Part A: Clinical and Molecular Teratology, 88:1008-1016; Springett et al. (2015); American Journal of Medical Genetics. Part A, 167A:3062-3069]. The solitary anterior malformation OMP has been reported as high as 6% with trisomy 18 [Springett et al. (2015); American Journal of Medical Genetics. Part A, 167A:3062-3069]. We report the third published case of CRN with concomitant OMP observed in a likely trisomy 18 fetus that screened positive by noninvasive prenatal screening. Furthermore, we review and analyze the current literature to augment understanding of the genetic basis for anterior and posterior closure defects such as CRN and OMP. Although the current genetic lexicon lacks any definitive association with the simultaneous defects presented, previous research elucidated various genes related to anterior or posterior closure interruption individually. By consolidating current research, the authors advance knowledge of interconnected genetic pathology and direct future genetic mapping efforts.