Embryologic Correlations

CASE 7: Holoprosencephaly

Clinical History:

A 38-year-old G2 P1 woman had a normal term infant last year. She has an ultrasound at 17 weeks in her current pregnancy. The fetal size equivalent is 15.3 weeks. The fetal brain appears abnormal, with only a single ventricle and fused thalami. Orbits are not seen. There is a midline cleft lip and palate. An extra digit is seen on each hand and foot. Amniocentesis is performed.

The fetus is stillborn at 21 weeks. Examination of the fetus shows cyclopia with a proboscis. Postaxial polydactyly is seen on all extremities.

  1. What is the name for the CNS abnormalities?

  2. The brain has the appearance of holoprosencephaly.

  3. Describe the embryology of the CNS abnormalities.

  4. The brain develops as the prosencephalon, mesencephalon, and metencephalon.

    The forebrain - prosencephalon - gives rise to the telencephalon and the diencephalon. Failure of complete development of the telencephalon precludes formation of two complete cerebral hemispheres. Instead, there is a single mass of brain with a single central cavity for a ventricle. When no hemispheric differentiation is present, the defect is called alobar holoprosencephaly. When there is at least partial development of hemispheres, the condition is called semilobar holoprosencephaly.

    The optic stalks and cups are diencephalic structures. Failure of complete development may lead to cyclopia.

    The thalamus is also a diencephalic structure. Fusion is typical for this condition.

  5. How does a cleft lip and palate occur?

  6. The primary (anterior) palate is derived from the intermaxillary segment. Most of the palate is the secondary (posterior) palate derived from outgrowths of the maxillary swellings known as the palatine shelves which fuse in the midline. The upper lip is form when the two medial nasal swellings and the two maxillary swellings merge. Failure of mesodermal penetration between the maxillary swellings anteriorly and/or failure of fusion of palatine shelves leads to a cleft.

  7. What is the karyotype likely to be?

  8. Trisomy 13 with a karyotype of: 47, XX, +13. This is also known as Patau syndrome.

  9. What is the prognosis with this type of condition?

  10. Chromosomal abnormalities most often lend to fetal loss, because excess genetic material or absent genetic material is poorly tolerated during fetal development. In fact most pregnancies are lost, but this often occurs in the first trimester and may not be noticed, except for a missed menstrual period.