A 32-year-old woman, gravida 1 para 0, at 35 weeks gestation comes to the emergency department due to absent fetal movement for the past 24 hours. The patient has had no prenatal care. Fetal ultrasonography confirms an intrauterine fetal demise. Autopsy examination of the fetus reveals incomplete separation of the cerebral hemispheres with a single ventricle, as shown in the image below: Which of the following is most closely associated with this fetal condition?

Question

A 32-year-old woman, gravida 1 para 0, at 35 weeks gestation comes to the emergency department due to absent fetal movement for the past 24 hours.  The patient has had no prenatal care.  Fetal ultrasonography confirms an intrauterine fetal demise.  Autopsy examination of the fetus reveals incomplete separation of the cerebral hemispheres with a single ventricle, as shown in the image below:  Which of the following is most closely associated with this fetal condition?

Quizplus · Accepted Answer

11ec160b_3749_13e1_9249_b505e444586d_MD0001_00 Fetal brain development begins at week 3, when the ectodermal cells thicken and invaginate to form the neural tube, which differentiates into the primitive forebrain (prosencephalon), midbrain (mesencephalon), and hindbrain (rhombencephalon). The prosencephalon gives rise to the diencephalon, which develops into the thalamus and third ventricle, and telencephalon, which develops into the cerebral hemispheres and lateral ventricles. This fetus has an incomplete separation of the cerebral hemispheres with a single lateral ventricle consistent with holoprosencephaly, a condition in which the forebrain fails to completely divide into right and left hemispheres. Disease severity and midline facial malformations (eg, facial clefts, cyclopia) are dependent upon the degree of hemisphere division; mild forms can be asymptomatic whereas severe cases can be lethal (as in this case). Holoprosencephaly may be due to a variety of factors (eg, sonic hedgehog gene mutations); the most common associated chromosomal abnormality is trisomy 13 (Patau syndrome). Other midline defects of trisomy 13 include microcephaly, microphthalmia, cleft lip/palate, and omphalocele. Cardiac abnormalities are also common, and cutis aplasia (scalp defect) is characteristic. The majority of affected fetuses die in utero. (Choice A) Congenital rubella syndrome may be fatal in utero or present in neonates with the characteristic triad of sensorineural hearing loss, cataracts, and congenital heart disease (eg, patent ductus arteriosus). Although CNS infection can result in microcephaly, holoprosencephaly is rare. (Choice B) Zika virus infection in utero causes infection of neural progenitor cells, resulting in impaired fetal brain development. Due to the destruction of the neurons, patients with congenital Zika virus infection typically have microcephaly, intracranial calcifications (a sign of tissue necrosis), and ventriculomegaly; holoprosencephaly is uncommon with Zika infection. (Choice C) Maternal lithium use is classically associated with fetal cardiac abnormalities (eg, Ebstein anomaly), not neurologic structural defects. (Choice E) Trisomy 21 (Down syndrome) can cause ventriculomegaly and decreased brain volume, but patients still have 2 separate cerebral hemispheres and ventricles (not holoprosencephaly). Educational objective: Holoprosencephaly is due to failure of the primitive forebrain (prosencephalon) to divide into the right and left hemispheres, resulting in a spectrum of brain and midface abnormalities (eg, facial clefts, cyclopia). Trisomy 13 is the most commonly associated etiology. __________ References: Syndromes associated with holoprosencephaly. (http://www.ncbi.nlm.nih.gov/pubmed/29770994)

A 32-Year-Old Woman, Gravida 1 Para 0, at 35 Weeks