Embryology of Occult Spinal Dysraphisms

  • Mark S. DiasEmail author
  • Elias B. Rizk


Writing a chapter on the embryology of occult spinal dysraphic malformations (OSDM) is a little like writing a historical fiction novel. We begin with a substantial knowledge about the cellular events, molecular biology, and biomechanics underlying normal avian and mammalian neural development – knowledge derived from a host of embryonic experimental manipulations and genetic mutations. From this we propose, largely by extension, a paradigm for normal human neural development that comports with our clinical observations and theorize about the embryogenesis of human neural tube defects (NTD) of myelomeningocele and exencephaly/anencephaly, for which we have reasonable experimental models. We are finally left to essentially fantasize about the embryogenesis of OSDM, for which we have virtually no animal models or experimental data. Many of the theories we will discuss in this chapter were created de novo decades ago from clinical observations and a basic understanding of morphogenesis, unmodified by subsequent advances in cellular and molecular biology. It is our hope that the future will bring greater clarity to our understanding about the embryogenesis of these malformations. Until then, a work of fiction will have to suffice.

We begin this chapter with an update about what is known about normal human embryogenesis and our present understanding about NTDs and then review present theories about the embryogenesis of various OSDM.


Embryology Occult spinal dysraphic malformations Neural tube defects Neurulation Dermal sinus tracts Spinal lipomas/lipomyelomeningocelees Spina bifida Split cord malformations Neurenteric cysts 


  1. 1.
    O’Rahilly R, Müller F. Developmental stages in human embryos. Washington, DC: Carnegie Institution of Washington; 1987.Google Scholar
  2. 2.
    Jellinger K, Gross H, Kaltenbäch E, Griswold W. Holoprosencephaly and agenesis of the corpus callosum: frequency of associated malformations. Acta Neuropathol. 1981;55:1–10.PubMedCrossRefGoogle Scholar
  3. 3.
    Vakaet L. Some new data concerning the formation of the definitive endoblast in the chick embryo. J Embryol Exp Morpholog. 1962;10:38–57.Google Scholar
  4. 4.
    Modak SP. Experimental analysis of the origin of the embryonic endoblast in birds. Rev Suisse Zool. 1966;73:877–908.PubMedGoogle Scholar
  5. 5.
    Fontaine J, Le Douarin NM. Analysis of endoderm formation in the avian blastoderm by the use of quail-chick chimaeras. The problem of the neurectodermal origin of the cells of the APUD system. J Embryol Exp Morpholog. 1977;41:209–22.Google Scholar
  6. 6.
    Rosenquist GC. A radioautographic study of labeled grafts in the chick blastoderm. Development from primitive streak stages to stage 12. Contrib Embryol. 1966;38(262):73–110.Google Scholar
  7. 7.
    Nicolet. Analyse autoradiographique de la localisation des différentes ébauches présomptives dans la ligne primitive de l’embryon de Poulet. J Embryol Exp Morpholog. 1970;23:79–108.Google Scholar
  8. 8.
    Nicolet G. Avian gastrulation. Adv Morph. 1971;9:231–62.CrossRefGoogle Scholar
  9. 9.
    Shaw W. Observations on two specimens of early human ova. Brit Med J. 1932;1:411–5.PubMedCrossRefGoogle Scholar
  10. 10.
    O’Rahilly R, Müller F. The first appearance of the human nervous system at stage 8. Anat Embryol. 1981;163:1–13.PubMedCrossRefGoogle Scholar
  11. 11.
    Müller F, O’Rahilly R. The development of the human brain and the closure of the rostral neuropore at stage 11. Anat Embryol. 1986;175:205–22.PubMedCrossRefGoogle Scholar
  12. 12.
    Müller F, O’Rahilly R. The first appearance of the neural tube and optic primordium in the human embryo at stage 10. Anat Embryol. 1985;172:157–69.PubMedCrossRefGoogle Scholar
  13. 13.
    Müller F, O’Rahilly R. The development of the human brain, the closure of the caudal neuropore, and the beginning of secondary neurulation at stage 12. Anat Embryol. 1987;176:413–30.PubMedCrossRefGoogle Scholar
  14. 14.
    O’Rahilly R. Developmental stages in human embryos, including a survey of the Carnegie collection. Part A: embryos of the first three weeks (stages 1 to 9), Carnegie Institution of Washington publication no. 631. Washington, DC: Carnegie Institution of Washington; 1973.Google Scholar
  15. 15.
    Müller F, O’Rahilly R. The first appearance of the major subdivisions of the human brain at stage 9. Anat Embryol. 1983;168:419–32.PubMedCrossRefGoogle Scholar
  16. 16.
    Golden JA, Chernoff GF. Multiple sites of anterior neural tube closure in humans: evidence from anterior neural tube defects (anencephaly). Pediatrics. 1995;95:506–10.PubMedGoogle Scholar
  17. 17.
    Golden JA, Chernoff GF. Intermittent pattern of neural tube closure in two strains of mice. Teratology. 1993;47:73–80.PubMedCrossRefGoogle Scholar
  18. 18.
    Van Allen MI, Kalousek DK, Chernoff GF, Juriloff D, Harris M, McGillivray BC, et al. Evidence for multi-site closure of the neural tube in humans. Am J Med Genet. 1993;47:723–43.PubMedCrossRefGoogle Scholar
  19. 19.
    Copp AJ, Greene NDE. Genetics and development of neural tube defects. J Pathol. 2010;220:217–30.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Müller F, O’Rahilly R. Cerebral dysraphia (future anencephaly) in a human twin embryo at stage 13. Teratology. 1984;30:167–77.PubMedCrossRefGoogle Scholar
  21. 21.
    Urioste M, Rosa A. Anencephaly and faciocranioschisis: evidence of complete failure of closure 3 of the neural tube in humans. Am J Med Genet. 1998;75:4–6.PubMedCrossRefGoogle Scholar
  22. 22.
    NIkolopoulou E, Galea GL, Rolo A, Greene NDE, Copp AJ. Neural tube closure: cellular, molecular and biomechanical mechanisms. Development. 2017;144:552–66.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Schoenwolf GC. Shaping and bending of the avian neuroepithelium: morphometric analyses. Dev Biol. 1985;109:127–39.PubMedCrossRefGoogle Scholar
  24. 24.
    Nicolopoulos-Stournaras S, Iles JF. Motor neuron columns in the lumbar spinal cord of the rat. J Comp Neurol. 1983;217:75–85.PubMedCrossRefGoogle Scholar
  25. 25.
    Schoenwolf GC, Smith JL. Mechanisms of neurulation: traditional viewpoint and recent advances. Development. 1990;109:243–70.PubMedGoogle Scholar
  26. 26.
    Smith JL, Schoenwolf GC. Notochordal induction of cell wedging in the chick neural plate and its role in neural tube formation. J Exp Zool. 1989;250:49–62.PubMedCrossRefGoogle Scholar
  27. 27.
    van Straaten HWM, Hekking JWM, Wiertz-Hoessels EJLM, Thors F, Drukker J. Effect of the notochord on the differentiation of a floor plate area in the neural tube of the chick embryo. Anat Embryol. 1988;177:317–24.PubMedCrossRefGoogle Scholar
  28. 28.
    Hammerschmidt M, Brook A, McMahon AP. The world according to hedgehog. Trends Genet. 1997;13:14–21.PubMedCrossRefGoogle Scholar
  29. 29.
    Rifat Y, Parekh V, Wilanowski T, Hislop NR, Auden A, Ting SB, et al. Regional neural tube closure defined by the Grainy head-like transcription factors. Dev Biol. 2010;345:237–45.PubMedCrossRefGoogle Scholar
  30. 30.
    George TM, McLone DG. Mechanisms of mutant genes in spina bifida: a review of implications from animal models. Pediatr Neurosurg. 1996;23:236–45.CrossRefGoogle Scholar
  31. 31.
    Chatkupt S, Johnson WG. Waardenburg syndrome and myelomeningocele in a family. J Med Genet. 1993;30:83–4.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Agopian AJ, Bhalla AD, Boerwinkle E, Finnell RH, Grove ML, Hixson JE, et al. Exon sequencing of PAX3 and T (brachyury) in cases with spina bifida. Birth Defects Res A Clin Mol Teratol. 2013;97:597–601.PubMedCrossRefGoogle Scholar
  33. 33.
    Zhao T, Gan Q, Stokes A, Lassiter RNT, Wang Y, Chan J, et al. β-catenin regulates Pax3 and Cdx2 for caudal neural tube closure and elongation. Development. 2014;141:148–57.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Schoenwolf GC. Tail (end) bud contributions to the posterior region of the chick embryo. J Exp Zool. 1977;201:227–46.CrossRefGoogle Scholar
  35. 35.
    Schoenwolf GC, DeLongo J. Ultrastructure of secondary neurulation in the chick embryo. Am J Anat. 1980;158:43–63.PubMedCrossRefGoogle Scholar
  36. 36.
    Schoenwolf GC. Histological and ultrastructural studies of secondary neurulation in mouse embryos. Am J Anat. 1984;169:361–76.PubMedCrossRefGoogle Scholar
  37. 37.
    Lemire RJ. Secondary caudal neural tube formation. In: Lemire RJ, Loeser JD, Leech RW, Ellsworth Jr CA, editors. Normal and abnormal development of the human nervous system. Hagerstown: Harper and Row; 1975. p. 71–83.Google Scholar
  38. 38.
    Bolli P. Sekundäre Lumenbildungen im Neuralrohr und Rückenmark menschlicher Embryonen. Acta Anat. 1966;64:48–81.CrossRefGoogle Scholar
  39. 39.
    Yang HJ, Lee DH, Lee YJ, Chi JG, Lee JY, Phi JH, et al. Secondary neurulation of human embryos: morphological changes and the expression of neuronal antigens. Childs Nerv Syst. 2014;30:73–82.PubMedCrossRefGoogle Scholar
  40. 40.
    Yang HJ, Wang KC, Chi JG, Lee MS, Lee YJ, Kim SK, et al. Neural differentiation of caudal cell mass (secondary neurulation) in chick embryos: Hamburger and Hamilton stages 16–45. Dev Brain Res. 2003;142:31–6.CrossRefGoogle Scholar
  41. 41.
    Chung YN, Lee DH, Yang HJ, Kim SK, Lee YJ, Lee MS, et al. Expression of neuronal markers in the secondary neurulation of chick embryos. Childs Nerv Syst. 2008;24:105–10.PubMedCrossRefGoogle Scholar
  42. 42.
    Beck CW. Development of the vertebrate tailbud. WIREs Dev Biol. 2015;4:33–44.CrossRefGoogle Scholar
  43. 43.
    van de Ven C, Bialecka M, Neijts R, Young T, Rowland JE, Stringer EJ, et al. Concerted involvement of Cdx/Hox genes and Wnt signaling in morphogenesis of the caudal neural tube and cloacal derivatives from the posterior growth zone. Development. 2011;138:3451–62.PubMedCrossRefGoogle Scholar
  44. 44.
    Dady A, Havis E, Escriou V, Catala M, Duband J-L. Junctional neurulation: a unique developmental program shaping a discrete region of the spinal cord highly susceptible to neural tube defects. J Neurosci. 2014;34:13208–21.PubMedCrossRefGoogle Scholar
  45. 45.
    Eibach S, Moes GS, Hou YJ, Zovickian J, Pang D. Unjoined primary and secondary neural tubes: junctional neural tube defect, a new form of spinal dysraphism caused by disturbance of junctional neurulation. Childs Nerv Syst. 2017;33:1633–47.PubMedCrossRefGoogle Scholar
  46. 46.
    Streeter GL. Factors involved in the formation of the filum terminale. Am J Anat. 1919;25:1–11.CrossRefGoogle Scholar
  47. 47.
    Kunimoto K. The development and reduction of the tail and of the caudal end of the spinal cord. Contrib Embryol. 1918;8:161–98.Google Scholar
  48. 48.
    DiPietro MA. The conus medullaris: normal US findings throughout childhood. Radiology. 1993;188:149–53.PubMedCrossRefGoogle Scholar
  49. 49.
    Wilson DA, Prince JR. MR imaging determination of the location of the normal conus medullaris throughout childhood. Am J Radiol. 1989;152:1029–32.Google Scholar
  50. 50.
    Wolfe S, Schneble F, Tröger J. The conus medullaris: time of ascendance to normal level. Pediatr Radiol. 1992;22:590–2.CrossRefGoogle Scholar
  51. 51.
    Barson AJ. The vertebral level of termination of the spinal cord during normal and abnormal development. J Anat. 1970;106:489–97.PubMedPubMedCentralGoogle Scholar
  52. 52.
    James CCM, Lassman LP. Spinal dysraphism. Spina bifida occulta. London: Butterworths; 1972.. 144 pGoogle Scholar
  53. 53.
    Barson AJ. Spina bifida: the significance of the level and extent of the defect to the morphogenesis. Dev Med Child Neurol. 1970;12:129–44.PubMedCrossRefGoogle Scholar
  54. 54.
    Kesler H, Dias MS, Kalapos P. The normal position of the conus medullaris in children: a whole-spine MRI study. Neurosurg Focus. 2007;23(2):1–5.CrossRefGoogle Scholar
  55. 55.
    Copp AJ, Greene NDE. Neural tube defects – disorders of neurulation and related embryonic processes. Wiley Interdiscip Rev Dev Biol. 2013;2:213–27.PubMedCrossRefGoogle Scholar
  56. 56.
    Ackerman LL, Menezes AH. Spinal congenital dermal sinuses: a 30-year experience. Pediatrics. 2003;112:641–7.PubMedCrossRefGoogle Scholar
  57. 57.
    Pang D, Zovickian J, Wong ST, Hou YJ, Moes GS. Limited dorsal myeloschisis: a not-so-rare form of primary neurulation defect. Childs Nerv Syst. 2013;29:1459–84.PubMedCrossRefGoogle Scholar
  58. 58.
    de Vloo P, Lagae L, Sciot R, Demaerel P, van Loon J, van Calenbergh F. Spinal dermal sinuses and dermal sinus-like stalks analysis of 14 cases with suggestions for embryologic mechanisms resulting in dermal sinus-like stalks. Eur J Paediatr Neurol. 2013;17:575–84.PubMedCrossRefGoogle Scholar
  59. 59.
    Eibach S, Moes GS, Zovickian J, Pang D. Limited dorsal myeloschisis associated with dermoid elements. Childs Nerv Syst. 2016;33:55–67.PubMedCrossRefGoogle Scholar
  60. 60.
    Dias MS, Partington MD. Congenital brain and spinal cord malformations and their associated cutaneous markers. Pediatrics. 2015;136:1105–19.CrossRefGoogle Scholar
  61. 61.
    Weprin BE, Oakes WJ. Coccygeal pits. Pediatrics. 2005;105:e69–73.CrossRefGoogle Scholar
  62. 62.
    Walker AE, Bucy PC. Congenital dermal sinuses; a source of spinal meningeal infection and subdural abscesses. Brain. 1934;57:401–21.CrossRefGoogle Scholar
  63. 63.
    Pang D, Dias MS. Cervical myelomeningoceles. Neurosurgery. 1993;33:363–73.PubMedGoogle Scholar
  64. 64.
    Aaronson I. Anterior sacral meningocele, anal canal duplication cyst and covered anus occurring in one family. J Pediatr Surg. 1970;5:559–63.PubMedCrossRefGoogle Scholar
  65. 65.
    Steinbok P. Dysraphic lesions of the cervical spinal cord. Neurosurg Clin N Am. 1985;6:367–76.CrossRefGoogle Scholar
  66. 66.
    Steinbok P, Cochrane DD. The nature of congenital posterior cervical or cervicothoracic midline cutaneous mass lesions. Report of eight cases. J Neurosurg. 1991;75:206–12.PubMedCrossRefGoogle Scholar
  67. 67.
    Ehni G, Love JG. Intraspinal lipomas: report of cases, review of the literature, and clinical and pathologic study. Arch Neurol Psychiatr. 1945;53:1–28.CrossRefGoogle Scholar
  68. 68.
    Lassman LP, James CCM. Lumbosacral lipomas: critical survey of 26 cases submitted to laminectomy. J Neurol Neurosurg Psychiatry. 1967;30:174–81.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    McLone DG, Mutluer S, Naidich TP. Lipomeningoceles of the conus medullaris. In: Raimondi AJ, editor. Concepts in pediatric neurosurgery. 3rd ed. Basel: S. Karger; 1983. p. 170–7.Google Scholar
  70. 70.
    Walsh JW, Markesbery WR. Histological features of congenital lipomas of the lower spinal canal. J Neurosurg. 1980;52:564–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Chapman PH. Congenital intraspinal lipomas: anatomical considerations and surgical treatment. Childs Brain. 1982;9:37–47.PubMedGoogle Scholar
  72. 72.
    Pang D. Long-term outcome of total and near-total resection of spinal cord lipomas and radical reconstruction of the neural placode: part I – surgical technique. Neurosurgery. 2009;65:511–29.PubMedCrossRefGoogle Scholar
  73. 73.
    Morota N, Ihara S, Ogiwara H. New classification of spinal lipomas based on embryonic stage. J Neurosurg Pediatr. 2017;19:428–39.CrossRefGoogle Scholar
  74. 74.
    Naidich TP, McLone DG, Mutluer S. A new understanding of dorsal dysraphism with lipoma (lipomyeloschisis): radiologic evaluation and surgical correction. Am J Roentgenol. 1983;140:1065–78.CrossRefGoogle Scholar
  75. 75.
    McLone DG, Naidich TP. Spinal dysraphism: experimental and clinical. In: Holtzman RN, Stein BM, editors. The tethered spinal cord. New York: Thieme-Stratton; 1985. p. 14–28.Google Scholar
  76. 76.
    French BN. Abnormal development of the central nervous system. In: McLaurin RL, Venes JL, Schut L, Epstein F, editors. Pediatric neurosurgery: surgery of the developing nervous system. 2nd ed. Philadelphia: W.B. Saunders Co.; 1989. p. 9–34.Google Scholar
  77. 77.
    George TM, Adamson DC. Normal and abnormal development of the nervous system. In: Albright AL, Pollack IF, Adelson PD, editors. Principles and practice of pediatric neurosurgery. New York: Thieme; 2015. p. 10–26.Google Scholar
  78. 78.
    Bentley JFR, Smith JR. Developmental posterior enteric remnants and spinal malformations. The split notochord syndrome. Am J Dis Child. 1960;35:76–86.CrossRefGoogle Scholar
  79. 79.
    Prop N, Frensdorf EL, van de Stadt FR. A postvertebral entodermal cyst associated with axial deformities: a case showing the “entodermal-ectodermal adhesion syndrome”. Pediatrics. 1967;39:555–62.PubMedGoogle Scholar
  80. 80.
    Bremer JL. Dorsal intestinal fistula; accessory neurenteric canal; diastematomyelia. Arch Pathol. 1952;54:132–8.Google Scholar
  81. 81.
    Cohen J, Sledge CB. Diastematomyelia. An embryological interpretation with report of a case. Am J Dis Child. 1960;100:127–33.CrossRefGoogle Scholar
  82. 82.
    Herren RY, Edwards JE. Diplomyelia (duplication of the spinal cord). Arch Pathol. 1940;30:1203–14.Google Scholar
  83. 83.
    Naidich TP, Harwood-Nash DC. Diastematomyelia: hemicord and meningeal sheaths; single and double arachnoid and dural tubes. Am J Neuroradiol. 1983;4:633–6.PubMedGoogle Scholar
  84. 84.
    James CCM, Lassman JP. Diastematomyelia. A critical survey of 24 cases submitted to laminectomy. Arch Dis Child. 1964;39:125–30.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Pang D. Split cord malformation: part II: the clinical syndrome. Neurosurgery. 1992;31:481–500.PubMedCrossRefGoogle Scholar
  86. 86.
    Pang D. Tethered cord syndrome. Neurosurgery: state of the art reviews. 1st ed. Philadelphia: Hanley and Belfus; 1986. p. 45–79.Google Scholar
  87. 87.
    Ross GW, Swanson SA, Perentes E, Urich H. Ectopic midline spinal ganglion in diastematomyelia: a study of its connections. J Neurol Neurosurg Psychiatry. 1988;51:1231–4.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Lichtenstein BW. “Spinal dysraphism”. Spina bifida and myelodysplasia. Arch Neurol. 1940;44:792–810.CrossRefGoogle Scholar
  89. 89.
    Rokos J. Pathogenesis of diastematomyelia and spina bifida. J Pathol. 1975;117:155–61.PubMedCrossRefGoogle Scholar
  90. 90.
    Dias MS, Walker ML. The embryogenesis of complex dysraphic malformations: a disorder of gastrulation? Pediatr Neurosurg. 1992;18:229–53.PubMedCrossRefGoogle Scholar
  91. 91.
    Gardner WJ. The dysraphic states from syringomyelia to anencephaly. Amsterdam: Excerpta Medica; 1973.. 201 pGoogle Scholar
  92. 92.
    Beardmore HE, Wigglesworth FW. Vertebral anomalies and alimentary duplications. Pediatr Clin N Am. 1958;5:457–74.CrossRefGoogle Scholar
  93. 93.
    Burrows FGO, Sutcliffe J. The split notochord syndrome. Br J Radiol. 1968;41:844–7.PubMedCrossRefGoogle Scholar
  94. 94.
    McLetchie NGB, Purves JK, Saunders RL. The genesis of gastric and certain intestinal diverticula and enterogenous cysts. Surg Gynecol Obstet. 1954;99:135–41.PubMedGoogle Scholar
  95. 95.
    Saunders RL. Combined anterior and posterior spina bifida in a living neonatal human female. Anat Rec. 1943;87:255–78.CrossRefGoogle Scholar
  96. 96.
    Dodds GS. Anterior and posterior rachischisis. Am J Pathol. 1941;17:861–72.PubMedPubMedCentralGoogle Scholar
  97. 97.
    Feller A, Sternberg H. Zur Kenntnis der Fehlbildungen der Wirbelsäule. I. Die Wirbelkörperspalte und ihre formale Genese. Virchow Arch Pathol Anat. 1929;272:613–40.CrossRefGoogle Scholar
  98. 98.
    Fernbach SK, Naidich TP, McLone DG, Leestma JE. Computed tomography of primary intrathecal Wilms tumor with diastematomyelia. J Comput Assist Tomogr. 1984;8:523–8.PubMedCrossRefGoogle Scholar
  99. 99.
    Cameron AH. Malformations of the neuro-spinal axis, urogenital tract and foregut in spina bifida attributable to disturbances of the blastopore. J Path Bact. 1957;73:213–21.CrossRefGoogle Scholar
  100. 100.
    Ugarte N, Gonzalez-Crussi F, Sotelo-Avila C. Diastematomyelia associated with teratoma. J Neurosurg. 1980;53:720–5.PubMedCrossRefGoogle Scholar
  101. 101.
    Emura T, Asashima M, Furue M, Hashizume K. Experimental split cord malformations. Pediatr Neurosurg. 2002;36:229–35.PubMedCrossRefGoogle Scholar
  102. 102.
    Emura T, Asashima M, Hashizume K. An experimental animal model of split cord malformation. Pediatr Neurosurg. 2000;33:283–92.PubMedCrossRefGoogle Scholar
  103. 103.
    Müller F, O’Rahilly R. Somitic-vertebral correlation and vertebral levels in the human embryo. Am J Anat. 1986;177:3–19.PubMedCrossRefGoogle Scholar
  104. 104.
    Peacock WJ, Murovic JA. Magnetic resonance imaging in myelocystoceles. Report of two cases. J Neurosurg. 1989;70:804–7.PubMedCrossRefGoogle Scholar
  105. 105.
    McLone DG, Naidich TP. Terminal myelocystocele. Neurosurgery. 1985;16:36–43.PubMedGoogle Scholar
  106. 106.
    Carey JC, Greenbaum B, Hall BD. The OEIS complex (omphalocele, extrophy, imperforate anus, spinal defects). Birth Defects. 1978;14(6B):253–63.PubMedGoogle Scholar
  107. 107.
    Lemire RJ, Beckwith JB. Pathogenesis of congenital tumors and malformations of the sacrococcygeal region. Teratology. 1982;25:201–13.PubMedCrossRefGoogle Scholar
  108. 108.
    Lee JY, Kim SP, Kim SW, Park S-H, Choi JW, Phi JH, et al. Pathoembryogenesis of terminal myelocystocele: terminal balloon in secondary neurulation of the chick embryo. Childs Nerv Syst. 2013;29:1683–8.PubMedCrossRefGoogle Scholar
  109. 109.
    Pang D, Zovickian J, Lee JY, Moes GS, Wang K-C. Terminal myelocystocele: surgical observations and theory of embryogenesis. Neurosurgery. 2012;70:1383–405.PubMedCrossRefGoogle Scholar
  110. 110.
    Passarge E, Lenz W. Syndrome of caudal regression in infants of diabetic mothers: observations of further cases. Pediatrics. 1966;37:672–4.PubMedGoogle Scholar
  111. 111.
    Alexander E, Nashold BS. Agenesis of the sacrococcygeal region. J Neurosurg. 1956;13:507–13.CrossRefGoogle Scholar
  112. 112.
    Frantz CH, Aitken GT. Complete absence of the lumbar spine and sacrum. JBJS. 1967;49-A:1531–40.CrossRefGoogle Scholar
  113. 113.
    Freedman B. Congenital absence of the sacrum and coccyx. Report of a case and review of the literature. Br J Surg. 1950;37:299–303.PubMedCrossRefGoogle Scholar
  114. 114.
    Hamsa WR. Congenital absence of the sacrum. Arch Surg. 1935;30:657–66.CrossRefGoogle Scholar
  115. 115.
    Pang D, Hoffman HJ. Sacral agenesis with progressive neurological deficit. Neurosurgery. 1980;7:118–26.PubMedCrossRefGoogle Scholar
  116. 116.
    Renshaw TS. Sacral agenesis. A classification and review of twenty-three cases. JBJS. 1978;60-A:373–83.CrossRefGoogle Scholar
  117. 117.
    Sarnat HB, Case ME, Graviss R. Sacral agenesis. Neurologic and neuropathologic features. Neurology. 1976;26:1124–9.PubMedCrossRefGoogle Scholar
  118. 118.
    Smith ED. Congenital sacral defects. In: Stephens FD, editor. Congenital malformations of the rectum, anus, and genito-urinary tracts. Edinburgh: E. & S. Livingstone; 1963. p. 82–105.Google Scholar
  119. 119.
    Rosselet P. A rare case of rachischisis with multiple malformations. Am J Roentgenol. 1955;73:235–40.Google Scholar
  120. 120.
    Stewart SF. Absence of sacrum with report of a case, and a review of the literature. Arch Surg. 1924;9:647–52.CrossRefGoogle Scholar
  121. 121.
    Williams DI, Nixon HH. Agenesis of the sacrum. Surg Gynecol Obstet. 1957;105:84–8.PubMedGoogle Scholar
  122. 122.
    Price DL, Dooling EC, Richardson EP. Caudal dysplasia (caudal regression syndrome). Arch Neurol. 1970;23:212–20.PubMedCrossRefGoogle Scholar
  123. 123.
    Rusnak SL, Driscoll SG. Congenital spinal anomalies in infants of diabetic mothers. Pediatrics. 1965;35:989–95.PubMedGoogle Scholar
  124. 124.
    Banta JV, Nichols O. Sacral agenesis. JBJS. 1969;51-A:693–703.CrossRefGoogle Scholar
  125. 125.
    Blumel J, Butler MC, Evans EB, Eggers GWN. Congenital anomaly of the sacrococcygeal spine. Arch Surg. 1962;85:982–93.PubMedCrossRefGoogle Scholar
  126. 126.
    Blumel J, Evans EB, Eggers GWN. Partial and complete agenesis or malformation of the sacrum with associated anomalies. JBJS. 1959;41-A:497–518.CrossRefGoogle Scholar
  127. 127.
    Ignelzi RJ, Lehman AW. Lumbosacral agenesis: management and embryological implications. J Neurol Neurosurg Psychiatry. 1974;37:1273–6.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Naik DR, Lendon RG, Barson AJ. A radiological study of vertebral and rib malformations in children with myelomeningocele. Clin Radiol. 1978;29:427–30.PubMedCrossRefGoogle Scholar
  129. 129.
    Lausecker H. Beitrag zu den mißbildungen des Kreuzbeines. Virchows Arch Path Anat. 1952;322:119–29.CrossRefGoogle Scholar
  130. 130.
    Lichtor A. Sacral agenesis. Report of a case. Arch Surg. 1947;54:430–3.PubMedCrossRefGoogle Scholar
  131. 131.
    Sinclair JG, Duren N, Rude JC. Congenital lumbosacral defect. Arch Surg. 1941;43:473–8.CrossRefGoogle Scholar
  132. 132.
    Girard PM. Congenital absence of the sacrum. JBJS. 1935;17:1062–4.Google Scholar
  133. 133.
    Källén B, Winberg J. Caudal mesoderm pattern of anomalies: from renal agenesis to sirenomelia. Teratology. 1974;9:99–112.PubMedCrossRefGoogle Scholar
  134. 134.
    Dias MS, Azizkhan RG. A novel embryonic mechanism for Currarino’s triad: inadequate dorsoventral separation of the caudal eminence from hindgut endoderm. Pediatr Neurosurg. 1998;28:223–9.PubMedCrossRefGoogle Scholar
  135. 135.
    Gaskill SJ, Marlin AE. The Currarino triad: its importance in pediatric neurosurgery. Pediatr Neurosurg. 1997;25:143–6.CrossRefGoogle Scholar
  136. 136.
    Lee S-C, Chun Y-S, Jung S-E, Park K-W, Kin W-K. Currarino triad: anorectal malformation, sacral bony abnormality, and presacral mass-a review of 11 cases. J Pediatr Surg. 1997;32:58–61.PubMedCrossRefGoogle Scholar
  137. 137.
    Ashcraft KW, Holder TM. Congenital anal stenosis with presacral teratoma: case reports. Ann Surg. 1965;162:1091–5.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Yates VD, Wilroy RS, Whitington GL, Simmons JCH. Anterior sacral defects: an autosomal dominantly inherited condition. J Pediatr. 1983;102:239–42.PubMedCrossRefGoogle Scholar
  139. 139.
    Cohn J, Bay-Nielsen E. Hereditary defect of the sacrum and coccyx with anterior sacral meningocele. Acta Paediatr Scand. 1969;58:268–74.PubMedCrossRefGoogle Scholar
  140. 140.
    Ross AJ, Ruiz-Perez V, Wang Y, Hagan DM, Scherer S, Lynch SA, et al. A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis. Nat Genet. 1998;20:358–61.PubMedCrossRefGoogle Scholar
  141. 141.
    Mills JL. Malformations in infants of diabetic mothers. Teratology. 1982;25:385–94.PubMedCrossRefGoogle Scholar
  142. 142.
    Duraiswami PK. Comparison of congenital defects induced in developing chickens by certain teratogenic agents with those caused by insulin. JBJS. 1955;37:277–94.CrossRefGoogle Scholar
  143. 143.
    Landauer W. Rumplessness of chicken embryos produced by the injection of insulin and other chemicals. J Exp Zool. 1945;98:65–77.CrossRefGoogle Scholar
  144. 144.
    Zwilling E. The effects of some hormones on development. Ann N Y Acad Sci. 1952;55:196–202.PubMedCrossRefGoogle Scholar
  145. 145.
    Horton WEJ, Sadler TW. Effects of maternal diabetes on early embryogenesis: alterations in morphogenesis produced by the ketone body, ß-hydroxybutyrate. Diabetes. 1983;32:610–6.PubMedCrossRefGoogle Scholar
  146. 146.
    Duhamel B. From the mermaid to anal imperforation: the syndrome of caudal regression. Arch Dis Child. 1961;36:152–5.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Wolff E. La Science des Monstres. Paris: Gallimard; 1948.Google Scholar
  148. 148.
    Gardner RJM, Nelson MM. An association of caudal malformations arising from a defect in the “axial mesoderm” developmental field. Am J Med Genet. 1986;2:37–44.CrossRefGoogle Scholar
  149. 149.
    Storm-Mathisen A. Myelodysplasia with absence of sacrum. Acta Psychiatr Neurol Scand. 1954;29:145–9.PubMedCrossRefGoogle Scholar
  150. 150.
    Bennett D. The T-locus of the mouse. Cell. 1975;6:441–54.CrossRefGoogle Scholar
  151. 151.
    Fontanella F, van Maarle MC, de Medina R, Oostra RJ, van Rijn RR, Pajkrt E, et al. Prenatal evidence of persistent notochord and absent sacrum caused by a mutation in the T (brachyury) gene. Case Rep Obstet Gynecol. 2016;2016:7625341.PubMedPubMedCentralGoogle Scholar
  152. 152.
    Pang D, Zovickian J, Moes GS. Retained medullary cord in humans: late arrest of secondary neurulation. Neurosurgery. 2011;68:1500–19.PubMedCrossRefGoogle Scholar
  153. 153.
    Colas J-F, Schoenwolf GC. Towards a cellular and molecular understanding of neurulation. Dev Dyn. 2001;221:117–45.PubMedCrossRefGoogle Scholar
  154. 154.
    Moury JD, Schoenwolf GC. Cooperative model of epithelial shaping and bending during avian neurulation: autonomous movements of the neural plate, autonomous movements of the epidermis, and interactions in the neural plate/epidermis transition zone. Dev Dyn. 1995;204:323–37.PubMedCrossRefGoogle Scholar
  155. 155.
    Dias MS, McLone DG. Normal and abnormal early development of the nervous system. In: McLone DG, editor. Pediatric neurosurgery: surgery of the developing nervous system. Philadelphia: W.B. Saunders; 2001. p. 31–71.Google Scholar
  156. 156.
    Moore KL. The developing human. 3rd ed. Philadelphia: W.B. Saunders Co.; 1982.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of NeurosurgeryPenn State Health Children’s HospitalHersheyUSA
  2. 2.Department of NeurosurgeryPenn State College of Medicine, Penn State Health Children’s HospitalHersheyUSA

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