Birth Defects, from an embryological perspective


This is a another subject where you might put your embryological knowledge to use, and improve medical methods to help babies and young children.

1) Many birth defects result from failure of normal morphogenetic cell movements.

Examples: Spina Bifida: Failure of neural folds to fuse in neurulation.

Cleft Palate: Failure of fusion of palatal shelves

Cleft Lip ("Hare Lip"): Failure of fusion of facial masses of dermis & epidermis

Septal defects (of the heart): Failure of fusion of sheets of tissue that normally separate right from left ventricles and atria.

Failure of archenteron to connect with the stomodeum

"Oropharyngeal Membrane" continues to block the throat.

Failure of thymus to form. (no 3rd and 4th pharyngeal pouches)

The general principle here is that "If anything can go wrong, it will"
(We need to find out how to say this in Latin or Greek, to make it sound more scientific)

For every normal event in embryonic development, there is likely to be a specific birth defect that is caused by failure of that event, or incomplete, or excess, versions of that event.

These birth defects make much more sense to a person who knows how embryos develop.
For example, spina bifida, cleft palate, etc. would seem to be caused by splitting apart of tissues; but really they are caused by failure of fusion of those tissues.

Many different heart defects occur; each makes sense in terms of some specific abnormality in the normal subdivision of the heart into right and left atria and right and left ventricles. For example, in some syndromes, the aorta or the pulmonary artery (or both) are connected to the right ventricle instead of the left, or vice-versa, or both. Such abnormalities result from the septum forming in the wrong places. (Visualize building a wall across a room, but mistakenly leaving some door on the wrong side of this wall.) The inter-ventricular septum can even fail to form at all. Or the foramen oval can be unable to close.

Because (as you have learned) the foramen oval and the ductus arterioles allow most blood to bypass the lungs, a heart without an interventricular septum can function OK, until birth.
Do you understand why?

But then what happens at birth?

Why are newborns with such abnormalities called "blue babies"?

Very great improvements in heart surgery on newborn babies have been accomplished.


#2) Structural defects in the body can also be produced by genetic defects in many genes, including collagen

Molecular Therapy (2008) 17 1, 26-33. "Injection of Recombinant Human Type VII Collagen Corrects the Disease Phenotype in a Murine Model of Dystrophic Epidermolysis Bullosa"
link to original article

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#3) Some chemicals cause birth defects. Alcohol, Thalidomide, cocaine, vitamin A (retinoic acid)

About 5 million US women were treated with diethylstilbestrol, because this chemical was thought (guessed!) to reduce the chance of miscarriage, (which it didn't), but it did produce severe birth defects in the uterus and related organs of their daughters

Fetal Alcohol Syndrome is a major cause of birth defects in babies of mothers who drank too much alcohol during pregnancy. Prof Cathy Sulik of UNC Med School is one of the best and most effective and respected researchers on this subject.

Other birth defects can result from not enough of certain chemicals. Increased folic acid can decrease the frequency of spina bifida by half!

The word "teratogen" means a chemical that causes (or can cause) birth defects.

Any chemical that is a "morphogen" will also be a teratogen. Do you see why?
(This is a very important concept.)

For each teratogen, there is (usually, always?) a certain time period of greatest susceptibility. (when it does the most harm; when the smallest concentration is able to produce harm.

Attempts to warn the public about teratogens have consistently caused strong political attacks on whichever scientists warned the public. Likewise Rachael Carson was targeted for intense personal attacks by editorials and news stories in Time, Newsweek etc. ( for which they apologized 10 years later.)


#4) Certain chemicals used in making plastics produce the same effects as estrogens (Female steroid sex hormones)


#5) Gain or loss of chromosomes ("Non-disjunction") often occurs during meiotic divisions of sperm precursor cells and oocytes.

In humans, all chromosomes losses (monosomy), and all but 3 gains of a chromosome ("trisomy") result in death of the developing embryos.

At least a fifth of human pregnancies end in miscarriage. (Spontaneous abortion)

Trisomy 21 (3 copies of the smallest chromosome) results in "Down syndrome". About a third of Down syndrome children survive until birth, and medical treatments for heart abnormalities and high leukemia rates now extend survival to ages of 50 or more.

The frequency having a Down Syndrome baby increases exponentially when the mother is older than 40. (5% at age 45, etc.)

The News and Observer organized an editorial campaign against me on this subject several years ago.

Try Googling "Conservapedia" ( and then "University of North Carolina at Chapel Hill". Then double-click on their article's reference number eleven.

What they say is a distortion; but the facts of the issue should be thought about and discussed by every pre-med student, and everyone who plans to have children. But don't believe the extremists on any side of this subject.

Having three copies of chromosome #21 results in transcribing 150% of the normal numbers of copies of all the genes on this chromosome, and making one and a half times as much of the proteins that they code for.

The excess of these proteins causes the physical abnormalities. Because of the genome project all these proteins have been identified.

Maybe you can discover a method for using either RNA-i or anti-sense RNA to help these children; or invent some other method. They are wonderfully sweet, trusting children, and deserve all the help you might be able to provide. Don't let hate groups discourage you from helping them.


Optional - NOT required reading! - but you may find this interesting:

Significant advances have been made recently in prenatal screening for birth defects. For example, spina bifida and other neural tube abnormalities in a developing fetus result in elevated levels of a specific protein in the mother's blood [more information]. The discovery a few years ago that fetal DNA fragments can also be detected in the mother's blood has led to development of a new test for chromosomal abnormalities that is very accurate and eliminates the risk of miscarriages induced by amniocentesis. For more on this test, see the following link: Click on the icon on the right ("Elsevier Full-Text Article") to get the text of the entire paper. This should work from on campus, or by logging in to the UNC system if you're off campus.


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