Transcription
Welcome to my congenital abnormality video. This tutorial was actually requested by my last class of medical students, and it's designed to introduce and hopefully clarify some confusing terms we use when we talk about different classes or types of congenital abnormalities. I'm Dr. Katherine Moore, the histology wizard, so let's start with the malformation.
The green circle here represents a primordium, which will grow into a structure, tissue, or organ that is represented by this white arrow. So a malformation, then, is an intrinsic defect; it's considered to be a production defect since something happens to alter the developmental process. So this could be a failure of embryonic formation, proliferation, or differentiation, and it usually happens early in development, most commonly in weeks three to eight. The end result is an abnormal structure that results from errors in formation. So one example of a malformation is the failure of the neural tube to close, and this can result in a myelomeningocele, which is a common neural tube defect.
Next up, we have deformation. Here we see a normal primordium, and the structure seems to be forming pretty normally, but there is now some kind of extrinsic defect that usually happens later in the in fetal life, generally speaking after organogenesis, where some kind of biomechanical force is going to alter the structure or the position of the organ or structure. So the end result, then, is an alteration in shape or position of that normal structure. One example of a deformation is intrauterine force that results in alteration of the normal foot structure, resulting in club foot, or the flattening of the face that we see in Potter sequence where there is too little amniotic fluid.
Disruptions also have a normal primordium and a normal growth process, or at least they have normal developmental potential. So again, we have an extrinsic event or defect, and this event is the or agent is going to interfere with normal development, and the growth process then becomes disrupted or discontinued, and there can actually be breakdown of the tissue. This is a perturbation of normal development, and there is actual destruction of existing tissue. Now a deformation can then lead to a secondary malformation, or it could be the start of a sequence, which I'll describe shortly. And really, the consequences depend upon the timing of the disruptive event. So one example here would be a constriction of a developing limb that disrupts growth, breaks down the tissue, and leads to a missing part of the limb.
Finally, we have dysplasia. Dysplasia is an intrinsic defect; it can be abnormal organization of cells or tissues or function, and dysplasia can actually happen prenatally or postnatally and essentially results in an abnormal model of the structure. Now, unlike the first three examples, dysplasia doesn't have to happen during a specific interval of development, and the clinical impacts can often get worse as the tissue continues to grow or functions. So here I'm showing a young boy with a skeletal dysplasia called achondroplasia, and here the dysplastic problem is with the cartilage, so that it doesn't form a normal bone model, and that leads to shorter bones.
Let's review: Malformations are intrinsic defects in the developmental process, and they can have multiple ideologies. Deformations happen later, alter normal growth, and are caused by external forces. Disruptions are also externally caused, with tissue or structure breakdown of tissue caused by vascular or compressive forces. Sometimes the degree of force actually determines whether we have a deformation or a disruption. And finally, we have dysplasia: intrinsic changes in the tissue or organ model.
Now, congenital abnormalities often occur in syndromes or sequences, and these terms can actually be quite confusing for students. So a syndrome is a collection of anomalies that are known as thought to have a common cause, such as a chromosomal abnormality in Down's syndrome. A syndrome can contain malformation, disruptions, deformations, sequences, and dysplasias, and they're generally recognized and diagnosed by pattern recognition and then confirmed by testing. A sequence, on the other hand, arises from a single embryological defect, such that A causes B, which leads to C and D. So sequences then have ordered consequences: if you never have A, then you don't get B, and these are obligate associations.
Let's look at a couple of examples. Treacher Collins syndrome has very characteristic facial anomalies, and it arises from a single defect in the TCOF1 gene, and there are many anomalies that can result from this mutation, although they don't all have to occur. So in Treacher Collins syndrome, there are also sequences. So let's take the example of bone hypoplasia: this can lead to dental abnormalities, but it can also lead to cleft palate, which leads to a restricted airway. Pierre Robin sequence starts with a single defect of lower jaw hypoplasia—that's A—which leads to a misplaced tongue—B—which fails to move out of the way in palate development, which then gives rise to cleft palate, and the cleft palate can lead to a restricted airway. So again, ordered consequences.
Finally, we have an association. In general, associations are patterns of anomalies that are seen together more often than would be predicted by chance. Most associations are thought to actually be syndromes—syndromes that we just haven't quite figured out what causes them. CHARGE syndrome was most considered an association until quite recently when researchers figured out the single gene mutation that led to all the abnormalities. Now there are very few associations; the most common is VACTERL, sometimes called VATER, where the anomalies you see here occur together more often than by chance. This is a very common boards question.
With that, we'll wrap up these general terms and mechanisms of congenital anomalies. I do hope that this tutorial helps clear up some confusion. Be sure to check out, like, and comment on my other videos. Suggestions and topics are always welcome. Thanks for stopping by.