A 35-year-old woman, gravida 2 para 0, is seen in the clinic for an early anatomy ultrasound at 18 weeks after she was noted to have an elevated alpha fetoprotein on prenatal screening. Ultrasound shows a complex cystic lesion overlying the lumbosacral spine, ventriculomegaly, and hindbrain herniation. These abnormalities are most likely due to failure of which of the following processes?
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This patient has an elevated alpha fetoprotein (AFP) level and ultrasound findings consistent with an open neural tube defect (NTD), a condition caused by failure of primary neurulation. Primary neurulation begins with formation of the neural plate. During the third week of fetal development, the lateral ends of the neural plate elevate to become neural folds that fuse in the midline to form the neural tube. Fusion starts in the cervical region and extends rostrally and caudally to the anterior and posterior neuropores, respectively.
Failure of either neuropore to close leads to open NTDs, in which a portion of the developing CNS remains connected to the amniotic cavity. Maternal serum AFP is elevated due to direct leakage from the open neural tube into the amniotic fluid.
Failure of posterior (caudal) neuropore closure specifically results in a NTD referred to as an open spinal dysraphism, and most commonly causes a myelomeningocele in which portions of the spinal cord within the meningeal sac protrude through a vertebral arch defect. Prenatal ultrasound may show a complex cystic mass along the lower spine, as in this case. Myelomeningoceles are also commonly associated with downward displacement of the hindbrain (Chiari II malformation) that can obstruct the flow of cerebrospinal fluid (causing ventriculomegaly).
(Choice A) The primitive streak establishes the anterior-posterior axis of the embryo; it normally completely disappears by the end of the 4th week of gestation. Rarely, remnants can persist in the sacrococcygeal region and give rise to a sacral teratoma. The brain would not be affected.
(Choice B) Dandy-Walker syndrome results from underdevelopment of the cerebellar vermis. Ultrasound would demonstrate cystic enlargement of the posterior fossa and hypoplasia of the vermis, and elevated AFP would not be expected.
(Choice C) Neural crest cells are the progenitors for the peripheral (not central) nervous system; Hirschsprung disease (congenital aganglionic megacolon) is a disorder of neural crest cell migration. NTDs are not related to neural crest cell abnormalities.
(Choice D) Neuronal migration disorders (eg, lissencephaly, or loss of sulci) are caused by the abnormal migration of nascent neurons within the brain. A spinal mass would not be seen.
Educational objective:
Defects in primary neurulation result in open neural tube defects, such as a myelomeningocele, in which the spinal cord and meninges protrude through a vertebral arch defect. Findings typically include an elevated maternal alpha fetoprotein and a complex cystic mass overlying the lower spine.