The “four Cs”

I use a sequential “four C” approach to the diagnosis of a child with congenital anomalies:

The bulk of this chapter deals with Step 1, collecting the data, which is primarily the process of history-taking and physical examination, often aided by laboratory investigations. Step 2 involves listing the pertinent positive features that have been found. If the diagnosis is not instantly obvious, move to the subsequent steps.

Congenital anomalies

Congenital anomalies have been noted throughout recorded history. Sculptures showing anomalies have been found dating back to 6500 bc, and records dating back to ancient Babylon indicate a keen awareness of congenital anomalies. However, it was only after 1966 that classification of an organized approach to these problems received serious attention. In that year, Dr. David W. Smith coined the term dysmorphology to refer to the clinical identification and assessment of structural anomalies, or “birth defects.” In the decades since then, much dysmorphology work was devoted to developing anomaly classification schemes. Such schemes help us understand at what point in development, and often how, the anomaly or constellation of anomalies occurred.

Isolated versus multiple defects

Begin to classify and categorize structural abnormalities by deciding whether the observed defect is isolated or is one of multiple defects. If the anomaly is an isolated one, few additional investigations will be necessary and, generally, the prognosis will be clear and management less complex. However, a child with multiple congenital anomalies represents a diagnostic challenge that may entail considerable investigation. The prognosis may be more grave, especially if the central nervous system (CNS) is involved. If a chromosomal or mendelian disorder is present, the family may face a significant risk of recurrence in a subsequent pregnancy. Further, management of the child is likely to be much more complicated, requiring coordination of care by multiple specialists. Thus the approach to the child with a cleft palate, a ventricular septal defect, or polydactyly is quite different from that for the child with all three anomalies.

Major anomalies

Next, differentiate between major and minor anomalies. Major malformations have serious cosmetic, surgical, or functional consequences. Examples are cleft lip, congenital heart defects, spina bifida, anencephaly, and gastrointestinal obstructions such as duodenal atresia and imperforate anus. Major anomalies involve structures, such as the CNS, heart, lungs, kidneys, gastrointestinal tract, and genitalia, and are detected readily when organ dysfunction develops. Assessment for internal anomalies may be triggered by signs found on physical examination, such as a heart murmur or a scaphoid abdomen accompanied by bowel sounds in the chest. The diagnosis, however, generally requires further investigations, such as imaging studies. Cardiac evaluation may require a chest radiograph, electrocardiogram, and echocardiogram; computed tomography or magnetic resonance imaging may be indicated to assess the CNS. Assessment of the limbs and spine often involves reviewing skeletal radiographs.

Minor anomalies

Although individual minor anomalies may not be surgically or medically significant, their existence is clinically important to dysmorphologists. The presence of several minor anomalies alerts the astute clinician to the possibility that more serious major defects also may be present. Although single minor anomalies are common in the general population, the occurrence of two in a single infant is less common, and the occurrence of three or more is cause for concern. Although minor anomalies occur more frequently than major ones, they often are overlooked.

Constellations of minor anomalies

Most minor anomalies are detected simply by careful observation—the key element of the dysmorphologic examination. When examining individual characteristics, each of which is a minor abnormality, remember that it is not so important that a particular feature is “abnormal.”

The constellation of minor anomalies gives the facies typical of certain so-called syndromes their characteristic appearance. In Down syndrome, for example, 79% of the malformations detectable by clinical examination are minor anomalies. When the diagnosis of Down syndrome is made, the “whole” (i.e., the constellation of minor anomalies) is more important than the sum of the individual parts. Many of these individual minor anomalies also can be found as isolated anomalies in perfectly “normal” people in the general population. This is where clinical experience plays an important role, because it often is easier to recognize individual anomalies than to spot the composite pattern that signals a particular syndrome.

Minor anomalies include upward- or downward-slanting palpebral fissures, small or low-set ears, ear tags or pits, clinodactyly (incurving of the finger, generally the fifth, often associated with a dysplastic middle phalanx), or widely spaced nipples. Variations in features found frequently in the population (in more than 4% of individuals) are considered normal variants, not minor anomalies. They include mild webbing (syndactyly) between the second and third toes (see Fig. 4-22) and hydroceles (i.e., fluid accumulation surrounding the testes). Because of the large numbers of minor anomalies and potential variations, it would be impractical to list them all here.

Nearly 50% of minor anomalies affect the head and face, reflecting both the complexity and variability of the structures involved. Remember the saying, “The face reflects the brain.” Craniofacial anomalies may be significant predictors of CNS abnormalities.

Anomalies are subdivided according to the mechanism of their abnormal morphogenesis, being classified as malformations, deformations, or disruptions. This classification poses the question of what happened in utero.

Malformations

A malformation is a structural defect caused by an intrinsic abnormality in the developmental process; that part of the body never developed normally. Malformations generally occur during the embryonic period and rarely correct spontaneously. Examples are anencephaly, spina bifida, cleft lip and palate, polydactyly, duodenal atresia, and congenital heart defects.

Deformations

A deformation, by contrast, is an abnormal shape, form, or position of a previously normally formed body part because of a mechanical force. Such forces generally result from uterine constraint because of insufficient amniotic fluid, malpresentation or uterine abnormalities, or lack of fetal movement. Sometimes the fetus is restrained; other times, severe neurologic problems cause the fetus to move less. Deformations generally arise later in the fetal period than malformations and often are corrected either spontaneously or through splinting. Examples are clubfoot, congenital hip dislocation, and some congenital contractures.

Disruptions

A disruption is a structural defect resulting from destruction of, or interference with, an originally normally formed body part. Typical examples are the anomalies produced by aberrant amniotic tissue bands that may cause amputation of digits, limb constrictions, or bizarre facial clefts. Vascular compromise also can lead to deprivation of blood supply to specific regions of the developing fetus, interfering with continued development. This process is thought to be the underlying cause of some unilateral limb reduction defects and of gastroschisis, an abdominal wall defect.

Sequences and syndromes

After categorizing a child’s defects as malformations, deformations, or disruptions, determining the developmental point at which they probably occurred, and arriving at a specific diagnosis, you turn to the next key question: Do the multiple anomalies seem to have occurred as a sequence, or do they likely represent a syndrome?

Dysmorphologists distinguish among different patterns of multiple anomalies as sequences and syndromes.

Comparing patterns

The number of recognizable patterns of structural abnormalities and syndromes is enormous, and more are being recognized all the time. The pattern, such as Down syndrome, may be familiar, but if it is not, take heart.

Even experienced dysmorphologists generally cannot remember all the anomalies that constitute any specific syndrome. The amount of information concerning the individual features of specific syndromes is simply too vast to memorize. Luckily, there are many useful reference books for comparing the patient’s characteristics with descriptions and photographs of identified syndromes. Perhaps the most widely used is Smith’s Recognizable Patterns of Human Malformation, which has invaluable tables listing the differential diagnosis of specific individual anomalies. These tables allow you to create a short list of syndromes that manifest as the particular anomalies you have identified in a given patient.

When using these tables to generate a list of diagnostic possibilities, start with the rarest and most distinctive feature you have noticed. Starting with features such as low-set ears or epicanthic folds would result in an unwieldy list, whereas starting with a white forelock or a dislocated lens would result in a more manageable list. Likewise, if all you identify are several very common features, such as short stature, a broad nasal bridge, and clinodactyly, you are not very likely to attain a specific diagnosis.

Several computer programs are now available that can generate such lists after a constellation of identified anomalies has been entered (see http://www.possum.net.au/ or http://www.lmdatabases.com/). These programs provide descriptions and often photographs of patients with different syndromes. The major advantage of using such programs is having access to their encyclopedic quality, but their usefulness is always limited by the accuracy of the history and physical findings that the physician “feeds” them. Computer programs cannot take the history or perform the physical examination; only a clinician can do this. Further, your clinical judgment is required to determine if any of the suggested diagnoses is, in fact, likely to be the correct one.

As a result of the many advances in our understanding of the molecular basis of development and the progress of the Human Genome Project, we are learning the genetic basis for many syndromes. Nevertheless, although we may know the molecular basis for a syndrome, we still may not have any diagnostic laboratory test for it. For some syndromes, a test may be available to confirm a diagnosis made on clinical grounds. (A useful resource for determining whether a genetic test is available for any particular syndrome is the GeneTests Web site: http://www.ncbi.nlm.nih.gov/sites/GeneTests/?db=GeneTests).

Despite your best efforts and the use of all diagnostic modalities, you may never reach a diagnosis. In fact, in more than half of children with multiple anomalies, no diagnosis can be established. Do not be afraid to admit that you cannot reach a diagnosis when that situation arises. Remember that assigning an incorrect diagnosis can be worse than not coming up with one. Sometimes, even though you may not be able to reach a diagnosis the first time you assess the child, over time and with repeated assessments—often as new features develop or reveal themselves—you will be able to do so. As you watch the natural history of the condition unfold, the diagnosis often becomes obvious.

History of pregnancy, labor, and delivery

Elements of a complete history that require special attention are the pregnancy, labor, delivery, and especially the family history.