A 28-year-old woman at 20 weeks gestation comes to the office for her first prenatal appointment. An ultrasound is performed, during which the fetus is found to have a congenital defect and no cardiac activity. Due to the pregnancy loss, the patient undergoes an induction of labor. After delivery, gross pathology of the fetus is shown in the exhibit. These findings are most likely due to an impairment in which of the following embryologic processes?
Show Explanatory Sources
The gross pathology of this fetus is consistent with anencephaly, an open neural tube defect (NTD). Open NTDs are caused by a defect in primary neurulation. This process normally begins with formation of the neural plate, the lateral ends of which elevate to become neural folds during the third week of fetal development. These folds form the neural tube by fusing in the midline, starting in the cervical region and extending rostrally and caudally to the anterior and posterior neuropores, respectively.
Failure of either neuropore to close results in an open NTD, and failure of anterior (rostral) neuropore closure specifically leads to anencephaly, a fatal condition in which the skull and meninges fail to form. The fetal brain is then exposed to amniotic fluid, resulting in degeneration of the developing forebrain, as seen here. Maternal serum alpha fetoprotein is markedly elevated due to direct leakage from the open neural tube into the amniotic fluid. Prenatal ultrasound shows absence of the brain and skull superior to the orbits.
Many fetuses with anencephaly die in utero; those born with anencephaly may retain spontaneous breathing and brainstem reflexes (eg, suck, Moro) but die soon after birth.
(Choice A) Neural crest cells are the progenitors for the peripheral nervous system and several other cell types (eg, melanocytes). Disorders of neural crest cell migration (eg, Hirschsprung disease) involve the peripheral nervous system rather than the CNS.
(Choice B) The notochord is a major regulator of embryonic patterning and disruption to its development may affect the CNS, gastrointestinal, or genitourinary tract. CNS structures related to notochord development include the spinal cord and vertebral column; defects would not affect the scalp and skull.
(Choice C) Failure of prosencephalon division leads to holoprosencephaly, in which the brain does not separate normally into 2 hemispheres. A spectrum of findings may be present, including hypotelorism, a single nostril or proboscis, and/or a single central incisor.
(Choice E) Failure of vertebral column fusion describes spina bifida occulta. Gross visual inspection may be unremarkable or show a deep sacral pit, tuft of hair, or overlying hemangioma.
Educational objective:
Open neural tube defects are a result of defects in primary neurulation (development and closure of the neural tube). Defective anterior (rostral) neuropore closure (eg, anencephaly) results in failure of the skull and meninges to form, allowing exposure of the developing brain to the destructive effects of amniotic fluid.