Neural tube defects

lower limbs and other major organ malformations.4 Complex dysraphic states due to aberrant integration of the notochord include split cord malformation (SCM) or diastematomyelia: a congenital spinal anomaly in which there is longitudinal splitting of the spinal cord.5,6 Causes of NTDs are multifactorial and defects in several different genes can underlie the genetic basis of this disease.1 However, inheritance is commonly polygenic with strong influencing environmental factors with strong implication of genes that regulate folate one-carbon metabolism and planar cell polarity. In Saudi Arabia and several other countries, consanguinity was suggested to contribute to the high incidence of NTDs.7 A higher proportion (20%) of syndromic NTDs, often associated with chromosomal anomalies, has also been documented compared with <10% elsewhere.7 The average incidence of NTDs is 1/1000 births, with a marked geographic variation and declining incidence in developed countries over recent decades. However, it remains high in the less-developed countries in Africa, Latin America, the Middle East, Asia, and the Far East (>1 to 11/1000 births).2 Recognized risk factors associated with NTDs include folate deficiency, maternal diabetes, obesity, maternal exposure to certain teratogens such as valproic acid and carbamazepine taken by mothers who have epilepsy, lead and tetrachloroethylene-contaminated drinking water, in utero exposure to arsenic, pesticides, mycotoxins, and fungus contaminants of maize, heat exposure, influenza, certain parental occupations, and low socioeconomic status.2 Most open NTDs are readily apparent at birth. Closed NTDs can present early with a cutaneous marker N tube defects (NTDs) constitute one of the most common malformations of human structure with a major public health burden (0.5-2/1000 pregnancies worldwide).1-3 They remain a preventable cause of still birth, neonatal and infant death, or significant lifelong handicaps. The underlying pathology is the consequence of a defect in the neurulation process very early in pregnancy, between 21 and 28 days after conception, leading to failure of the neural folds to fuse in the midline and form the neural tube.1 Secondary abnormal development of the mesoderm, responsible for forming the skeletal and muscular structures that cover the underlying neural structures, follows resulting in dysraphism, which indicates persistent continuity between the posterior neural ectoderm and cutaneous ectoderm. Based on embryological considerations and the presence or absence of exposed neural tissue, NTDs are classified as open or closed types. Cranial dysraphism (failure of cranial neural tube closure) includes anencephaly and encephaloceles, whereas spinal dysraphism (due to failure of caudal neuropore closure) is divided into open spinal dysraphisms (myelomeningocele, myelocele, hemimyelocele, and hemimyelomeningocele) and closed spinal dysraphisms. The latter can be associated with subcutaneous mass and includes lipomas with dural defect and meningocele. Complex dysraphic states are disorders characterized by aberrant formation or integration of the notochord, which is the inductor of the neural ectoderm and constitutes the foundation of the axial skeleton.1 These include caudal regression syndrome, which ranges from agenesis of the coccyx to absence of the sacral, lumbar, and lower thoracic vertebrae; to sirenomelia (or mermaid syndrome) characterized by fusion of the