A 35-year-old woman, gravida 2 para 1, comes to the office for a routine prenatal visit. Her first child was born with a hydrocele and syndactyly of the first and second toes. The patient has no significant medical conditions and takes no medications except for a multivitamin. Examination shows clear lungs and normal S1 and S2 heart sounds. The abdomen is soft and nontender. Uterine size, fetal movements, and fetal cardiac activity are all within normal limits. The patient undergoes an amniocentesis at 18 weeks gestation. Amniotic fluid analysis shows an increased level of acetylcholinesterase. This patient's amniocentesis results most likely suggest failure of which of the following processes?
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Patients at increased risk for congenital defects (eg, maternal age ≥35) may be offered amniocentesis for prenatal diagnosis. Amniotic fluid consists primarily of fetal urine; therefore, it can contain fetal serum proteins such as alpha-fetoprotein (AFP). Amniotic fluid does not usually contain acetylcholinesterase (AChE), an enzyme normally concentrated in the cerebrospinal fluid (CSF). Therefore, elevated AChE on amniocentesis suggests a leak of fetal CSF into the amniotic cavity known as an open neural tube defect (NTD).
NTDs occur due to failed fusion of the neural plate edges during the fourth week of fetal development. Fusion begins in the cervical region and proceeds toward the cranial and caudal ends of the neural tube (ie, rostral and caudal neuropores). Failed rostral neuropore closure causes anencephaly, and failed caudal neuropore closure causes spina bifida. A persistent opening between the neural tube and the amniotic cavity allows leakage of AFP and AChE into the amniotic fluid. AFP can also cross the placenta and become elevated in the maternal serum.
(Choice A) Duodenal atresia results from impaired recanalization of the duodenum due to failure of epithelial cell apoptosis. It causes elevated amniotic fluid volume but not elevated AChE on amniocentesis. The syndactyly of the patient's first child is also an example of failed apoptosis of mesenchyme between the digits.
(Choices C, E, and F) Failed involution of the thyroglossal tract can cause a persistent thyroglossal duct cyst. Hirschsprung disease involves failed neural crest cell migration into the sigmoid colon/rectum. Failure of the processus vaginalis to obliterate can lead to congenital hydrocele or indirect inguinal hernia. None of these conditions are associated with increased AChE in the amniotic fluid because they do not involve a persistent opening between the fetal neural tube and the amniotic cavity.
(Choice D) Advanced maternal age is a risk factor for Down syndrome (meiotic nondisjunction of chromosome 21), which presents with low AFP and normal AChE levels in the amniotic fluid.
Educational objective:
Neural tube defects (NTDs) most often occur when the neural folds fail to fuse in the region of the anterior or posterior neuropores. An open NTD allows leakage of alpha-fetoprotein and acetylcholinesterase into the amniotic fluid, leading to elevated levels detected on amniocentesis.