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Neural tube defect(NTD)

MedGen UID:
18009
Concept ID:
C0027794
Congenital Abnormality
Synonyms: Neural tube defects; NTD
SNOMED CT: Neural tube defect (253098009); NTD - Neural tube defect (253098009)
 
Genes (locations): CCL2 (17q12); FUZ (19q13.33); TBXT (6q27); VANGL1 (1p13.1); VANGL2 (1q23.2)
 
HPO: HP:0045005
Monarch Initiative: MONDO:0018075
OMIM®: 182940
Orphanet: ORPHA3388

Definition

Neural tube defects are the second most common type of birth defect after congenital heart defects. The 2 most common NTDs are open spina bifida, also known as spina bifida cystica (SBC) or myelomeningocele, and anencephaly (see 206500) (Detrait et al., 2005). Spina bifida occulta (SBO), a bony defect of the spine covered by normal skin, is a mild form of spina bifida that is often asymptomatic. The term 'spinal dysraphia' refers to both SBC and SBO (Botto et al., 1999; Fineman et al., 1982). The most severe neural tube defect, craniorachischisis (CRN), leaves the neural tube open from the midbrain or rostral hindbrain to the base of the spine (summary by Robinson et al., 2012). Neural tube defects represent a complex trait with multifactorial etiology encompassing both genetic and environmental components (summary by Bartsch et al., 2012 and Lei et al., 2014). An X-linked form of spina bifida has been suggested; see 301410. See also folate-sensitive neural tube defects (601634), which are caused by genes involved in folate metabolism. [from OMIM]

Additional descriptions

From MedlinePlus Genetics
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.

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.  https://medlineplus.gov/genetics/condition/spina-bifida
From MedlinePlus Genetics
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.

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.  https://medlineplus.gov/genetics/condition/anencephaly

Clinical features

From HPO
Urinary incontinence
MedGen UID:
22579
Concept ID:
C0042024
Finding
Loss of the ability to control the urinary bladder leading to involuntary urination.
Lipoma
MedGen UID:
44173
Concept ID:
C0023798
Neoplastic Process
Benign neoplasia derived from lipoblasts or lipocytes of white or brown fat. May be angiomatous or hibernomatous.
Multiple lipomas
MedGen UID:
677074
Concept ID:
C0745730
Finding
The presence of multiple lipomas (a type of benign tissue made of fatty tissue).
Anencephaly
MedGen UID:
8068
Concept ID:
C0002902
Congenital Abnormality
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.\n\nBecause these nervous system abnormalities are so severe, almost all babies with anencephaly die before birth or within a few hours or days after birth.\n\nBecause 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.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Myelomeningocele
MedGen UID:
7538
Concept ID:
C0025312
Congenital Abnormality
Protrusion of the meninges and portions of the spinal cord through a defect of the vertebral column.
Spina bifida occulta
MedGen UID:
36380
Concept ID:
C0080174
Congenital Abnormality
The closed form of spina bifida with incomplete closure of a vertebral body with intact overlying skin.
Absence of the sacrum
MedGen UID:
83373
Concept ID:
C0344490
Congenital Abnormality
Absence (aplasia) of the sacrum.
Asymmetry of spinal facet joints
MedGen UID:
870231
Concept ID:
C4024669
Anatomical Abnormality
Sacral dimple
MedGen UID:
98428
Concept ID:
C0426848
Finding
A cutaneous indentation resulting from tethering of the skin to underlying structures (bone) of the intergluteal cleft.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Conditions with this feature

Anophthalmia plus syndrome
MedGen UID:
322166
Concept ID:
C1833339
Disease or Syndrome
A very rare multiple congenital anomaly syndrome with characteristics of anophthalmia or severe microphthalmia, cleft lip/palate, facial cleft and sacral neural tube defects, along with various additional anomalies including congenital glaucoma, iris coloboma, primary hyperplastic vitreous, hypertelorism, low-set ears, clinodactyly, choanal atresia/stenosis, dysgenesis of sacrum, tethering of spinal cord, syringomyelia, hypoplasia of corpus callosum, cerebral ventriculomegaly and endocrine abnormalities. An autosomal recessive inheritance has been suggested.
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10
MedGen UID:
767295
Concept ID:
C3554381
Disease or Syndrome
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. The brain shows cobblestone lissencephaly, a cortical malformation. The phenotype includes the alternative clinical designations Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB). The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (summary by Vuillaumier-Barrot et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
Blepharocheilodontic syndrome 1
MedGen UID:
1632198
Concept ID:
C4551988
Disease or Syndrome
The blepharocheilodontic syndrome is a rare autosomal dominant disorder characterized by lower eyelid ectropion, upper eyelid distichiasis, euryblepharon, bilateral cleft lip and palate, and conical teeth. An additional rare manifestation is imperforate anus (summary by Weaver et al., 2010).

Professional guidelines

PubMed

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
Douglas Wilson R, Van Mieghem T, Langlois S, Church P
J Obstet Gynaecol Can 2021 Jan;43(1):124-139.e8. Epub 2020 Nov 17 doi: 10.1016/j.jogc.2020.11.003. PMID: 33212246
Mandel AM
Handb Clin Neurol 2020;171:291-311. doi: 10.1016/B978-0-444-64239-4.00015-1. PMID: 32736756

Recent clinical studies

Etiology

Fons K, Jnah AJ
Neonatal Netw 2021 Aug 1;40(5):313-320. doi: 10.1891/11-T-704. PMID: 34518383
Kiani AK, Paolacci S, Calogero AE, Cannarella R, Di Renzo GC, Gerli S, Della Morte C, Busetto GM, De Berardinis E, Del Giudice F, Stuppia L, Facchinetti F, Dinicola S, Bertelli M
Eur Rev Med Pharmacol Sci 2021 Mar;25(5):2390-2402. doi: 10.26355/eurrev_202103_25279. PMID: 33755975
Ferrazzi E, Tiso G, Di Martino D
Eur J Obstet Gynecol Reprod Biol 2020 Oct;253:312-319. Epub 2020 Jun 13 doi: 10.1016/j.ejogrb.2020.06.012. PMID: 32868164
Lee S, Gleeson JG
Trends Neurosci 2020 Jul;43(7):519-532. Epub 2020 May 15 doi: 10.1016/j.tins.2020.04.009. PMID: 32423763Free PMC Article
van Gool JD, Hirche H, Lax H, De Schaepdrijver L
Reprod Toxicol 2018 Sep;80:73-84. Epub 2018 May 16 doi: 10.1016/j.reprotox.2018.05.004. PMID: 29777755

Diagnosis

Erdoğan K, Sanlier NT, Sanlier N
J Nutr Sci 2023;12:e103. Epub 2023 Sep 26 doi: 10.1017/jns.2023.62. PMID: 37771507Free PMC Article
Fons K, Jnah AJ
Neonatal Netw 2021 Aug 1;40(5):313-320. doi: 10.1891/11-T-704. PMID: 34518383
Douglas Wilson R, Van Mieghem T, Langlois S, Church P
J Obstet Gynaecol Can 2021 Jan;43(1):124-139.e8. Epub 2020 Nov 17 doi: 10.1016/j.jogc.2020.11.003. PMID: 33212246
Markovic I, Bosnjakovic P, Milenkovic Z
Curr Pediatr Rev 2020;16(3):200-205. doi: 10.2174/1573396315666191018161535. PMID: 31656152Free PMC Article
Chitayat D, Matsui D, Amitai Y, Kennedy D, Vohra S, Rieder M, Koren G
J Clin Pharmacol 2016 Feb;56(2):170-5. Epub 2015 Nov 5 doi: 10.1002/jcph.616. PMID: 26272218Free PMC Article

Therapy

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
Sanz Cortes M, Chmait RH, Lapa DA, Belfort MA, Carreras E, Miller JL, Brawura Biskupski Samaha R, Sepulveda Gonzalez G, Gielchinsky Y, Yamamoto M, Persico N, Santorum M, Otaño L, Nicolaou E, Yinon Y, Faig-Leite F, Brandt R, Whitehead W, Maiz N, Baschat A, Kosinski P, Nieto-Sanjuanero A, Chu J, Kershenovich A, Nicolaides KH
Am J Obstet Gynecol 2021 Dec;225(6):678.e1-678.e11. Epub 2021 Jun 3 doi: 10.1016/j.ajog.2021.05.044. PMID: 34089698
van Gool JD, Hirche H, Lax H, De Schaepdrijver L
Reprod Toxicol 2018 Sep;80:73-84. Epub 2018 May 16 doi: 10.1016/j.reprotox.2018.05.004. PMID: 29777755
Chitayat D, Matsui D, Amitai Y, Kennedy D, Vohra S, Rieder M, Koren G
J Clin Pharmacol 2016 Feb;56(2):170-5. Epub 2015 Nov 5 doi: 10.1002/jcph.616. PMID: 26272218Free PMC Article
Lancet 1991 Jul 20;338(8760):131-7. PMID: 1677062

Prognosis

Lu VM
Childs Nerv Syst 2023 Nov;39(11):3103-3109. Epub 2023 May 13 doi: 10.1007/s00381-023-05985-2. PMID: 37178370
Akyol ME, Çelegen I, Basar I, Arabacı O
Eur Rev Med Pharmacol Sci 2022 Aug;26(15):5399-5405. doi: 10.26355/eurrev_202208_29407. PMID: 35993634
Sanz Cortes M, Chmait RH, Lapa DA, Belfort MA, Carreras E, Miller JL, Brawura Biskupski Samaha R, Sepulveda Gonzalez G, Gielchinsky Y, Yamamoto M, Persico N, Santorum M, Otaño L, Nicolaou E, Yinon Y, Faig-Leite F, Brandt R, Whitehead W, Maiz N, Baschat A, Kosinski P, Nieto-Sanjuanero A, Chu J, Kershenovich A, Nicolaides KH
Am J Obstet Gynecol 2021 Dec;225(6):678.e1-678.e11. Epub 2021 Jun 3 doi: 10.1016/j.ajog.2021.05.044. PMID: 34089698
Markovic I, Bosnjakovic P, Milenkovic Z
Curr Pediatr Rev 2020;16(3):200-205. doi: 10.2174/1573396315666191018161535. PMID: 31656152Free PMC Article
Chitayat D, Matsui D, Amitai Y, Kennedy D, Vohra S, Rieder M, Koren G
J Clin Pharmacol 2016 Feb;56(2):170-5. Epub 2015 Nov 5 doi: 10.1002/jcph.616. PMID: 26272218Free PMC Article

Clinical prediction guides

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
Sanz Cortes M, Chmait RH, Lapa DA, Belfort MA, Carreras E, Miller JL, Brawura Biskupski Samaha R, Sepulveda Gonzalez G, Gielchinsky Y, Yamamoto M, Persico N, Santorum M, Otaño L, Nicolaou E, Yinon Y, Faig-Leite F, Brandt R, Whitehead W, Maiz N, Baschat A, Kosinski P, Nieto-Sanjuanero A, Chu J, Kershenovich A, Nicolaides KH
Am J Obstet Gynecol 2021 Dec;225(6):678.e1-678.e11. Epub 2021 Jun 3 doi: 10.1016/j.ajog.2021.05.044. PMID: 34089698
Kiani AK, Paolacci S, Calogero AE, Cannarella R, Di Renzo GC, Gerli S, Della Morte C, Busetto GM, De Berardinis E, Del Giudice F, Stuppia L, Facchinetti F, Dinicola S, Bertelli M
Eur Rev Med Pharmacol Sci 2021 Mar;25(5):2390-2402. doi: 10.26355/eurrev_202103_25279. PMID: 33755975
Lee S, Gleeson JG
Trends Neurosci 2020 Jul;43(7):519-532. Epub 2020 May 15 doi: 10.1016/j.tins.2020.04.009. PMID: 32423763Free PMC Article
Chitayat D, Matsui D, Amitai Y, Kennedy D, Vohra S, Rieder M, Koren G
J Clin Pharmacol 2016 Feb;56(2):170-5. Epub 2015 Nov 5 doi: 10.1002/jcph.616. PMID: 26272218Free PMC Article

Recent systematic reviews

Viswanathan M, Urrutia RP, Hudson KN, Middleton JC, Kahwati LC
JAMA 2023 Aug 1;330(5):460-466. doi: 10.1001/jama.2023.9864. PMID: 37526714
Vena F, D'Ambrosio V, Paladini V, Saluzzi E, Di Mascio D, Boccherini C, Spiniello L, Mondo A, Pizzuti A, Giancotti A
J Matern Fetal Neonatal Med 2022 Dec;35(25):7296-7305. Epub 2021 Jul 5 doi: 10.1080/14767058.2021.1946789. PMID: 34219595
Atlaw D, Tekalegn Y, Sahiledengle B, Seyoum K, Solomon D, Gezahegn H, Tariku Z, Tekle Y, Chattu VK
BMC Pregnancy Childbirth 2021 Jun 14;21(1):426. doi: 10.1186/s12884-021-03848-9. PMID: 34126936Free PMC Article
Viswanathan M, Treiman KA, Kish-Doto J, Middleton JC, Coker-Schwimmer EJ, Nicholson WK
JAMA 2017 Jan 10;317(2):190-203. doi: 10.1001/jama.2016.19193. PMID: 28097361
Wald NJ, Hackshaw AD, Stone R, Sourial NA
Br J Obstet Gynaecol 1996 Apr;103(4):319-24. doi: 10.1111/j.1471-0528.1996.tb09735.x. PMID: 8605127

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