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Neural tube defects, folate-sensitive(NTDFS)

MedGen UID:
355746
Concept ID:
C1866558
Disease or Syndrome
Synonyms: NTD, FOLATE-SENSITIVE; NTDFS
 
Genes (locations): MTHFD1 (14q23.3); MTHFR (1p36.22); MTR (1q43); MTRR (5p15.31)
 
Monarch Initiative: MONDO:0011120
OMIM®: 601634

Definition

Neural tube defects have a birth incidence of approximately 1 in 1,000 in American Caucasians and are the second most common type of birth defect after congenital heart defects. The most common NTDs are open spina bifida (myelomeningocele) and anencephaly (206500) (Detrait et al., 2005). Women with elevated plasma homocysteine, low folate, or low vitamin B12 (cobalamin) are at increased risk of having a child with a neural tube defect (O'Leary et al., 2005). Motulsky (1996) cited evidence from the Centers for Disease Control ( Anonymous, 1992) that folic acid given before and during the first 4 weeks of pregnancy can prevent 50% or more of neural tube defects. Botto et al. (1999) and Detrait et al. (2005) provided reviews of neural tube defects. De Marco et al. (2006) provided a detailed review of neurulation and the possible etiologies of neural tube defects. [from OMIM]

Additional descriptions

From MedlinePlus Genetics
Anencephaly is a condition that prevents the normal development of the brain and the bones of the skull. This condition results when a structure called the neural tube fails to close during the first few weeks of embryonic development. The neural tube is a layer of cells that ultimately develops into the brain and spinal cord. Because anencephaly is caused by abnormalities of the neural tube, it is classified as a neural tube defect.

Because the neural tube fails to close properly, the developing brain and spinal cord are exposed to the amniotic fluid that surrounds the fetus in the womb. This exposure causes the nervous system tissue to break down (degenerate). As a result, people with anencephaly are missing large parts of the brain called the cerebrum and cerebellum. These brain regions are necessary for thinking, hearing, vision, emotion, and coordinating movement. The bones of the skull are also missing or incompletely formed.

Because these nervous system abnormalities are so severe, almost all babies with anencephaly die before birth or within a few hours or days after birth.  https://medlineplus.gov/genetics/condition/anencephaly
From MedlinePlus Genetics
In a milder form of the condition, called spina bifida occulta, the bones of the spinal column are abnormally formed, but the nerves of the spinal cord usually develop normally. Unlike in the more severe form of spina bifida, the spinal cord does not stick out through an opening in the spine. Spina bifida occulta most often causes no health problems, although rarely it can cause back pain or changes in bladder function.

Children born with spina bifida often have a fluid-filled sac on their back that is covered by skin, called a meningocele. If the sac contains part of the spinal cord and its protective covering, it is known as a myelomeningocele. The signs and symptoms of these abnormalities range from mild to severe, depending on where the opening in the spinal column is located and how much of the spinal cord is contained in the sac. Related problems can include a loss of feeling below the level of the opening, weakness or paralysis of the feet or legs, and problems with bladder and bowel control. Some affected individuals have additional complications, including a buildup of excess fluid around the brain (hydrocephalus) and learning problems. With surgery and other forms of treatment, many people with spina bifida live into adulthood.

Spina bifida is a condition in which the neural tube, a layer of cells that ultimately develops into the brain and spinal cord, fails to close completely during the first few weeks of embryonic development. As a result, when the spine forms, the bones of the spinal column do not close completely around the developing nerves of the spinal cord. Part of the spinal cord may stick out through an opening in the spine, leading to permanent nerve damage. Because spina bifida is caused by abnormalities of the neural tube, it is classified as a neural tube defect.  https://medlineplus.gov/genetics/condition/spina-bifida

Clinical features

From HPO
Spinal dysraphism
MedGen UID:
87487
Concept ID:
C0344479
Congenital Abnormality
A heterogeneous group of congenital spinal anomalies that result from defective closure of the neural tube early in fetal life.
Abnormality of metabolism/homeostasis
MedGen UID:
867398
Concept ID:
C4021768
Finding

Professional guidelines

PubMed

Wilson RD, O'Connor DL
J Obstet Gynaecol Can 2022 Jun;44(6):720-732.e1. doi: 10.1016/j.jogc.2022.04.003. PMID: 35691684
Wilson RD, O'Connor DL
J Obstet Gynaecol Can 2022 Jun;44(6):707-719.e1. doi: 10.1016/j.jogc.2022.04.004. PMID: 35691683

Recent clinical studies

Etiology

Wilson RD, O'Connor DL
J Obstet Gynaecol Can 2022 Jun;44(6):720-732.e1. doi: 10.1016/j.jogc.2022.04.003. PMID: 35691684
Wilson RD, O'Connor DL
J Obstet Gynaecol Can 2022 Jun;44(6):707-719.e1. doi: 10.1016/j.jogc.2022.04.004. PMID: 35691683

Diagnosis

Wilson RD, O'Connor DL
J Obstet Gynaecol Can 2022 Jun;44(6):720-732.e1. doi: 10.1016/j.jogc.2022.04.003. PMID: 35691684
Wilson RD, O'Connor DL
J Obstet Gynaecol Can 2022 Jun;44(6):707-719.e1. doi: 10.1016/j.jogc.2022.04.004. PMID: 35691683

Therapy

Wilson RD, O'Connor DL
J Obstet Gynaecol Can 2022 Jun;44(6):720-732.e1. doi: 10.1016/j.jogc.2022.04.003. PMID: 35691684
Wilson RD, O'Connor DL
J Obstet Gynaecol Can 2022 Jun;44(6):707-719.e1. doi: 10.1016/j.jogc.2022.04.004. PMID: 35691683

Clinical prediction guides

Wilson RD, O'Connor DL
J Obstet Gynaecol Can 2022 Jun;44(6):720-732.e1. doi: 10.1016/j.jogc.2022.04.003. PMID: 35691684
Wilson RD, O'Connor DL
J Obstet Gynaecol Can 2022 Jun;44(6):707-719.e1. doi: 10.1016/j.jogc.2022.04.004. PMID: 35691683

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