Neural Tube Defects, Folate-Sensitive

Alternative Names

  • NTD, Folate-Sensitive
  • Spina Bifida, Folate-Sensitive
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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Congenital malformations of the nervous system

OMIM Number

601634

Mode of Inheritance

? Autosomal recessive

Gene Map Locus

1p36.22, 1q43,5p15.31,14q23.3

Description

The development of the neural tube in the mammalian embryo is a tightly regulated process controlled by multiple genes that can be modulated by environmental perturbations. Etiologic factors frequently associated with neural tube defects include chromosomal abnormalities, single gene defects, maternal diabetes, and anticonvulsant drugs, although it is generally agreed that most neural tube defects are multifactorial in origin. Recent studies have suggested that the risk of having a child with neural tube defect due to a gene and/or nutrient interaction is largely preventable by periconceptional supplements with folic acid.

The pathogenetic mechanisms underlying neural tube defect risk remain poorly understood. Whereas the vast majority of neural tube defects result from a primary failure of the neural tube to properly close. About 80% of embryos surviving up to nine weeks with neural tube defects have been reported to have concurrent chromosomal abnormalities. Interestingly, trisomy has been found to be the most common chromosomal anomaly associated with neural tube defects.

Molecular Genetics

The MTHFR 677 C-T polymorphism decreases enzyme activity and raises the dietary requirement for folic acid to maintain normal remethylation of homocysteine to methionine. Chronic elevation in intracellular homocysteine can lead to an increase in SAH and potent product inhibition of the DNA methyltransferase leading to DNA hypomethylation. DNA hypomethylation during embryogenesis has been proposed to negatively affect chromatin structure and critical regulatory genes required for normal development. There is also evidence that chronic folate/methyl deficiency can lead to chromosome instability, and aberrant chromosome segregation.

Epidemiology in the Arab World

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Other Reports

Arab

Al Talabani et al. (1998) studied the pattern of major congenital malformations in 24,233 consecutive live and stillbirth at the only maternity hospital in Abu Dhabi, between January 1992 and January 1995. A total of 401 babies (16.6/1,000), including 289 Arabs, were seen with major malformation.  In their study, Al Talabani et al. (1998) observed 12 cases with neural tube defects from the United Arab Emirates. Recurrence was not reported in other members of the families. 

Al-Gazali et al. (1999) prospectively studied 9,610 births in the three major hospitals in Al-Ain, United Arab Emirates (UAE) between October 1995 and January 1997. Of the 225 babies with congenital anomalies identified, 31 had central nervous system (CNS) abnormalities (3.2/1000). Neural tube defect was detected  in 11 cases (36%). 

Bahrain

Al-Arrayed (Personal communication, Dubai, 2006) indicated that the average incidence rate of neural tube defects in Bahrain for the years 1991-2000 is 2.68 per 1000 births (1991: 3.3, 1992: 3.2, 1993 and 1994: 2.2, 1995: 2.0, 1996: 2.6, 1997: 2.1, 1998: 3.6, 1999: 3.0, 2000: 2.6, respectively).

Oman

Rajab et al. (1998) carried out a retrospective study to determine the incidence of neural tube defects (NTD) and congenital hydrocephalus (CH) in Oman. National data retrieved from hospital records revealed the incidence of NTD in Oman to be comparatively low (1.25 per 1000).  Rajab et al. (1998) observed a much higher consanguinity rates in families with NTD and CH than in the general population.

Palestine

Dudin (1997) conducted a preliminary study to estimate the incidence of neural tube defect (NTD) among Palestinians living in East Jerusalem and the southern part of the West Bank (600,000 inhabitants). Between 1 January 1986 and 31 December 1993, there were 148 cases of NTD, an incidence of 5.49 per 1000 births. The female to male ratio was 1.5:1. The incidence of NTD increased with maternal age.

In 1997, Zlotogora analyzed 2000 Palestinian Arabic families and found that in 98 families at least one individual had congenital hydrocephalus and/or open neural tube defect. In 76 of the families the neural tube defect and/or the hydrocephalus were non-syndromal. In 47 families at least one individual was affected with an open neural tube defect. 

Saudi Arabia

The overall incidence of neural tube defects (NTDs) over nine years (1997-2005) at a university hospital in Jeddah was reported by Safdar et al. (2007) to be 1.3/1000 live births. The total number of babies born with NTDs was 42, and the male to female ratio was 1.1:1. The study shows a decline in the incidence of NTDs from 1.9/1000 live births in the period (1997-2000) to 0.76/1000 live births in the period (2001-2005). The decline seemed to coincide with the folic acid flour fortification in the Kingdom. Information about consanguinity could be obtained for 26 cases only, and of these 50% (13 babies) had consanguineous parents.

Sudan

Nugud et al. (2003) conducted a restrospective study of 43 patients with neural tube fusion defects. They did not find significant difference in male and female ratio. Maternal diabetes was reported in 9% of cases. The sib recurrence rate was 7.0%. Nugud et al. (2003) concluded that neural tube defects have a higher incidence during winter in Sudan and mostly in the first born child.

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