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Spina bifida

Abstract

Spina bifida is a birth defect in which the vertebral column is open, often with spinal cord involvement. The most clinically significant subtype is myelomeningocele (open spina bifida), which is a condition characterized by failure of the lumbosacral spinal neural tube to close during embryonic development. The exposed neural tissue degenerates in utero, resulting in neurological deficit that varies with the level of the lesion. Occurring in approximately 1 per 1,000 births worldwide, myelomeningocele is one of the most common congenital malformations, but its cause is largely unknown. The genetic component is estimated at 60–70%, but few causative genes have been identified to date, despite much information from mouse models. Non-genetic maternal risk factors include reduced folate intake, anticonvulsant therapy, diabetes mellitus and obesity. Primary prevention by periconceptional supplementation with folic acid has been demonstrated in clinical trials, leading to food fortification programmes in many countries. Prenatal diagnosis is achieved by ultrasonography, enabling women to seek termination of pregnancy. Individuals who survive to birth have their lesions closed surgically, with subsequent management of associated defects, including the Chiari II brain malformation, hydrocephalus, and urological and orthopaedic sequelae. Fetal surgical repair of myelomeningocele has been associated with improved early neurological outcome compared with postnatal operation. Myelomeningocele affects quality of life during childhood, adolescence and adulthood, posing a challenge for individuals, families and society as a whole. For an illustrated summary of this Primer, visit: http://go.nature.com/fK9XNa

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Figure 1: Overview of neural tube defects.
Figure 2: Neurulation and the origin of open and closed spinal bifida.
Figure 3: MRI appearance of brain dysmorphology in myelomeningocele.
Figure 4: Myelomeningocele and associated cranial signs on ultrasonography.
Figure 5: Fetal surgery for spina bifida.
Figure 6: Quality-of-life concerns across developmental stages in patients with spina bifida.
Figure 7: Folate metabolism and possible interventions.

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Acknowledgements

The authors acknowledge grants from The Wellcome Trust (grant 087525 to A.J.C.), the Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Institutes of Health (grants U10 HD041666 to N.S.A., P01 HD35946 to J.M.F. and R01-HD048629 to G.N.H.) and the March of Dimes Foundation (grant 12-FY13-271 to G.N.H.). Images of human embryonic material are provided by the Joint Medical Research Council–Wellcome Trust Human Developmental Biology Resource (www.hdbr.org; grant 099175).

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Introduction (A.J.C.); Epidemiology (G.M.S.); Mechanisms/pathophysiology (A.J.C. and J.M.F.); Diagnosis, screening and prevention (G.M.S. and L.S.C.); Management (N.S.A.); Quality of life (G.N.H.); Outlook (A.J.C. and G.N.H.); overview of Primer (A.J.C.).

Corresponding author

Correspondence to Andrew J. Copp.

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Competing interests

G.M.S. has received consulting fees from: Advanced Micro Devices and NXP Semiconductors for semiconductor employment and birth defects; GlaxoSmithKline for paroxetine use and birth defects; and Vivus, Inc. for topiramate use and oral clefts. A.J.C., N.S.A., L.S.C., J.M.F. and G.N.H. declare no competing interests.

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Copp, A., Adzick, N., Chitty, L. et al. Spina bifida. Nat Rev Dis Primers 1, 15007 (2015). https://doi.org/10.1038/nrdp.2015.7

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