Recent perspectives on the genetic background of neural tube defects with special regard to iniencephaly

Abstract

Iniencephaly is a rare and mostly lethal type of neural tube defect. The pattern of inheritance of this group of malformations is multifactorial, rendering the identification of the underlying causes. Numerous studies have been conducted to elucidate the genetic basis of human neurulation. Essential signaling pathways of the development of the CNS include the planar cell polarity pathway, which is important for the initiation of neural tube closure, as well as the sonic hedgehog pathway, which regulates the neural plate bending. Genes influencing the different stages of neurulation have been investigated for their eventual role in the development of these malformations. Among the environmental factors, folic acid seems to be the most important modifier of the risk of human neural tube defects. Genes of the folate metabolism pathways have also been investigated to identify mutations resulting in increased risk of neural tube defects. In this review we have attempted to summarize the knowledge on iniencephaly and neural tube defects, with special regard to genetic factors of the etiology.

First trimester three-dimensional ultrasound diagnosis of iniencephaly. A case report with review of literature

“…In ver- tebrates, this pathway plays a key role in establishing and maintaining a coordinated polarized orientation of the cells necessary for numerous developmental procedures, including directional movements during vertebrate gastrulation and neurulation (6,7) . Furthermore, mutations in Hox homeobox family of genes and problems with Pax-1 gene expression could be at the origin of this very unusual malformation (8) . Few cases 2% were associated with a chromosomal anomaly, especially trisomy 18, 13 and mosaicism for a marker chromosome in one.…”

Missing links between genetically inherited molecules in split cord malformation and other anomaly: A bench to bedside approach

“…[ 12 ] Failure of neuroepithelial folding at the DLHP has loss of Grhl3 alone, which defined the distinct lower spinal closure defect. [ 13 ] DLHP formation genes contribute equally to closure 2, and only Grhl gene dosage is limiting. Deletion of Grhl2 and Grhl3 induces rostral and caudal neural tube defects.…”

Neural Tube Defects: Review of Experimental Evidence on Stem Cell Therapy and Newer Treatment Options

“…The exact mechanism of NTDs is not known at present, but a range of mouse mutant models, especially the curly tail (ct) mutant which mimics human malformations in location, pathology and associated abnormalities and loop tail mutant which manifests into craniorachischisis, have greatly enhanced our understanding of NTDs in humans [1,2] . Several excellent reviews from time to time have elaborated the role of different genes in the neurulation process in general as well in folate metabolism pathway [3][4][5][6][7][8] . Extracellular matrix, cell surface glycoproteins, actin-containing microfilaments, growth factors and coor- dinated action of several genes have been implicated in the neurulation process.…”