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.

Obtaining The History

To make the proper diagnosis required to manage the patient and counsel the family, the clinician must elicit accurate and complete information.

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.

Pregnancy History

The pregnancy history is outlined in Chapters 1 and 4. Be sure to relate calendar dates to gestation time. For example, note that the mother had a viral illness at 7 gestational weeks, not “on January 16.” Specifically inquire about the course of the pregnancy.

Ask about fetal growth. Were any size-date discrepancies noted? Did fetal growth rate seem to diminish? Uterine size may provide clues to both fetal growth and fetal physiology. Polyhydramnios (i.e., increased amniotic fluid volume) indicates either increased fetal urine excretion or, more typically, difficulties with fetal swallowing that may be seen with fetal neuromuscular disease, gastrointestinal tract obstruction, or heart failure. Lack of fundal growth may indicate intrauterine growth retardation or oligohydramnios. As mentioned earlier, one cause of the latter is poor fetal renal function. The deformations associated with the oligohydramnios sequence could be expected. Information from prenatal ultrasound examinations may help assess these situations, because other fetal anomalies, fetal position and activity, or uterine abnormalities may have been recognized at the time of the ultrasonography.

Significant Questions

1. Were any prenatal studies performed, such as amniocentesis, chorionic villus sampling, nuchal translucency, detailed ultrasonography, maternal serum screening, or cordocentesis?

2. Did the mother or father experience any chronic medical problems, such as diabetes, seizures, phenylketonuria or other metabolic diseases, or idiopathic thrombocytopenic purpura?

3. Did any accidents, illnesses (such as fever or infections), or unusual events, such as medical or dental procedures, occur during the pregnancy?

4. Did any potentially harmful environmental exposures occur during the pregnancy, such as to hormones, drugs (prescription, over-the-counter, and those frequently abused), cigarettes, alcohol, chemicals, fumes (at work and at home), heat (hot tubs, saunas, and fever), or radiation?

Explore these last issues carefully and delicately, and document them. Modern society is preoccupied with the role of environmental factors as a cause of birth defects, and misconceptions regarding the relationships between environmental exposures and congenital anomalies are common. For example, we know that diagnostic radiography hardly ever involves exposure to radiation doses high enough to cause anomalies. Because inquiries about such procedures, although important, may increase parental anxiety and guilt about such exposures, be prepared to inform the families about these issues when you ask these questions.

Key Point

Remember: Few agents are proven teratogens, although equally few have been proved safe.

Labor and Delivery History

When asking about the labor and delivery, keep several points in mind. Although breech delivery occurs in 3% to 4% of pregnancies, it is more common in the presence of particular syndromes. Breech presentation may be caused by the fetus’s inability to move into the correct position, and in utero it may indicate that CNS damage is causing fetal motor weakness. Similarly, a difficult birth and asphyxia may not be the cause of a child’s problems but the result of them. For example, it is now well established that cerebral palsy, which often is attributed to obstetric difficulties and perinatal asphyxia, is in most instances due to fetal abnormalities that long antedated delivery.

Although the anomalies found on physical examination may help substantiate the diagnosis—which may have medicolegal implications—historic data also may help.

Key Point

Asking about historical data, such as the onset, strength, and frequency of fetal movements, helps bolster a diagnosis of congenital neuromuscular abnormalities.

Fetal movement usually is felt at 16 weeks’ gestation. Although the amount of movement is variable and the mother’s perceptions are subjective, fetal movement normally is strong enough at some point to hurt the mother and to be visible to the father. An experienced mother can compare the strength and frequency of fetal movement in one pregnancy to that in previous pregnancies. Feeble, rare, or unusual movements or lack of change in fetal position may indicate neuromuscular dysfunction or fetal constraint, in which case congenital contractures or positional deformations might be expected. In the evaluation of an asphyxiated dysmorphic newborn, a history of abnormal movements may help distinguish the effects of congenital neuromuscular abnormalities from those of intrapartum events.

Family history

The first step in taking the family history is to make the family feel comfortable. It does not help much to ask the parents whether there are any inherited disorders in the family, because that question presumes they understand genetics, effectively asking them to make diagnoses. Also, inquiring about similarly affected individuals in the family may increase the parents’ feelings of guilt and anxiety.

I prefer to begin by asking questions about the parents themselves. Because at this point any chronic or pregnancy-related health problems have been discussed, now is the time to ask about the parents’ ages at the time of the child’s birth. Advanced maternal age (generally held to be more than 35 years) is associated with a higher risk for chromosomal abnormalities (aneuploidies), whereas advanced paternal age may be associated with a higher risk for new dominant mutations (and therefore disorders such as achondroplasia).

Key Point

A 35-year-old woman has a 1 in 200 risk of having a chromosomally abnormal child; the risk rises to 1 in 65 at 40 years and 1 in 20 at 45 years.

Next, ask about previous pregnancies. Were there any spontaneous abortions, stillbirths, or problems in conceiving? Recurrent loss of pregnancies (i.e., multiple miscarriages), as well as stillbirth, particularly of a malformed child, often is a clue to a familial chromosome rearrangement. Although about 50% of spontaneous abortions occurring in the first trimester involve chromosomal anomalies, most occur sporadically. However, in about 5% of couples who have experienced three or more spontaneous abortions, a chromosomal rearrangement is found in one of the partners.

Sketch out the family pedigree, covering, in general, three generations. Using the details of pedigree construction and the appropriate pedigree symbols (found in any introductory genetics textbook), begin with the parents, recording each pregnancy and the outcome (including stillbirths and miscarriages) in chronologic order, from eldest to youngest, from left to right. The easiest way to stay organized is to begin in the middle of the page. An example is shown in Figure 5-1.

FIGURE 5-1 A sample pedigree from a consanguineous family of a child with Smith-Lemli-Opitz syndrome (child indicated by arrow and solid square). See text for explanation of symbols.

The convention in drawing a pedigree is that the male partner is drawn on the left. Circles are used to designate females, squares are used for males, and diamonds are used when the sex is not known. Affected individuals are indicated by solid figures and carriers by half-shaded figures. Deceased individuals are shown by a diagonal line through the symbol. Horizontal lines represent matings, and a double one is used for consanguineous matings. Vertical lines denote offspring. Indicate the proband, that is, the child you are assessing, with an arrow pointing to the pedigree symbol. Take note not only of full siblings of the proband but also of half-siblings from any previous union of either parent. Record the four grandparents, their other children (i.e., the parents’ siblings) and, finally, the child’s first cousins (the children of the parents’ siblings). Then document the health of each individual. Note the age of all those living and the date and age at death of deceased family members.

Next, determine whether there is any consanguinity. Remember that the risk of both autosomal recessive and multifactorial conditions rises when the parents are consanguineous. Start by directly asking the parents whether their families are related to each other (by blood). You might phrase the question by asking one parent, “Is anyone in your family related to anyone in your partner’s family?” This question may not lead to the correct answer, however. As I record the pedigree, I note last names, maiden names, and birthplaces that may raise the possibility of consanguinity. In people who come from small communities, parents often are unaware of consanguinity; it can help to know whether both parents’ families come from the same community and whether any family names appear on both sides of the family. When there is consanguinity, a pedigree usually illustrates the relationship more clearly than trying to describe it (e.g., “the parents are third cousins once removed”).

Ascertain the family’s ethnic background, because that information may provide valuable clues to a diagnosis. Certain disorders occur at higher frequency among particular ethnic groups, and some disorders are virtually limited to a specific group. The carrier frequency for Tay-Sachs disease among Jews of Eastern European descent, for example, is 10 times higher than in the general population. Italians, Greeks, and others of Mediterranean descent are at higher risk for carrying a gene for β-thalassemia; families of Asian descent may carry a gene for α-thalassemia. Approximately 8% of North American blacks carry the sickle cell gene.

Before completing the family history, I ask specifically about any instances in the extended family of multiple miscarriages, stillbirths, infertility, neonatal deaths (especially unexplained ones), birth defects, or mental retardation. Because the words mental retardation have an emotional impact, it often is better to ask whether anyone in the family has had “learning problems” or “schooling difficulties.” A history of multiple males in the mother’s family affected with mental retardation may suggest the fragile X syndrome; this is the most common genetic cause of mental retardation, and its diagnosis can have important implications for genetic counseling. Testing using cytogenetic and molecular studies can be triggered by the recognition of a pedigree pattern suggesting X-linked inheritance.

Ask about any conditions that run in the family and also about anomalies similar to those in the child. When the situation warrants, examine the parents and other relatives to uncover evidence of similar but perhaps more subtle manifestations of the same disorder. Whenever possible, obtain copies (with appropriate consent, of course) of family members’ medical records to confirm any important diagnoses the family discloses. Accurate documentation of the precise pathology and age at diagnosis can be extremely important, for example, in assessing for the possibility of a familial cancer syndrome.

Growth and development history

Although congenital means “present at birth,” some congenital anomalies may not become evident and detectable, or may not be evaluated, until later in life. Obviously, in such cases the history of the present illness must include a description of the evolution of the child’s problems, evaluation and management of the problems, and information about the child’s growth and development.

Key Point

Developmental delay is always an indication for a morphologic examination, because 42% of patients with idiopathic mental retardation have three or more malformations, of which 80% are minor.

If the child’s development seems to have proceeded normally for a time, followed by a deterioration of development, the cause of the problem may be a neurodegenerative process rather than a structural brain malformation. Understanding progressive changes in appearance, growth patterns, and behavior makes clear the general nature of the underlying process. Specific questions to ask include the following:

• How is the child’s vision?

• How is the child’s hearing?

• Does the child have any history of seizures?

Specific unusual behavior characteristics and patterns also may provide clues to an underlying diagnosis. An example of these so-called behavioral phenotypes is the superficial sociability and “cocktail party chatter” of persons with Williams syndrome. Children with Prader-Willi syndrome display compulsive overeating and unusual food-seeking and hoarding behaviors. They may be stubborn, have temper tantrums, and display other compulsive behaviors, such as picking at the skin. They also may be described as having an unusual skill at solving jigsaw puzzles. Children with the Smith-Magenis syndrome typically have sleep disturbances and self-injurious behavior but also exhibit unusual features, such as self-hugging and repetitive (“lick and flip”) page-turning of books.

Approach To the Physical Examination

What is normal?

The most difficult aspect of the physical examination, especially for a dysmorphology examination, is learning what is “normal.” It has become apparent, with the deciphering of the human genome, that there is actually no such thing as a completely normal individual. Indeed, it has been suggested (only slightly facetiously) that a normal person is someone who has not yet been adequately investigated. Remember that genetics is the study of human variation, and a wide range of variation exists for each characteristic considered “normal.” It takes experience to appreciate dysmorphic features and to know where normal variation ends and minor abnormality begins. The more normal infants you examine, the more comfortable you will feel about making this distinction. The computer programs mentioned earlier, such as POSSUM, include a DVD with thousands of photographs of dysmorphic features; they also often are useful in helping you gain an appreciation of the range and description of these features.

Consider the appearance of both parents when trying to determine whether a particular feature is unusual. As previously mentioned, ethnic background can be important. For example, before concluding that a particular child’s upslanting palpebral fissures and epicanthal folds are dysmorphic, ask whether the parent not present at the examination is of Asian descent; if the answer is yes, these features are to be expected. If the child’s father is not present, ask the mother if she has a photograph of him with her. Similarly, if a parent says, “Jeffrey looks just like his Uncle Steven did when he was that age,” do not just accept the statement; ask to see both old and recent photographs of Uncle Steven. Perusing the family photograph album, looking especially at old baby pictures, can be rewarding; it helps establish rapport with the family and is a nonthreatening way to compare the child’s features with those of other family members. This rapport will be very important when the time comes to break the news to the family of the diagnosis you have reached.

Do not be fooled, however. Even when a child shares certain features with a parent, sibling, or a parent’s sibling, do not exclude the possibility that these are minor abnormalities. While almost any minor anomaly may simply be familial, the parent also may have an undiagnosed, milder form of the same autosomal dominant syndrome.

If all the grandparents agree that the child does not take after either side of the family, examine the baby more closely. A child’s dysmorphic features may be quite subtle and not immediately distinctive. More often, however, the dysmorphic child’s appearance is clearly different from that of other (unaffected) family members.

Nevertheless, it also is important to bear in mind the considerable variability of syndromes and genetic disorders. The features of various syndromes also vary with age. Often, even within the same family, two affected individuals may have quite different manifestations. Sometimes the particular features observed in another affected family member may help you establish the diagnosis if these features are absent in the child. Just as you need to appreciate the range of normal variation, you also must recognize the variability of these disorders. Although obvious, distinctive features may make the diagnosis of a particular syndrome easy, those features may be rare, even in an affected child. More common features may be more likely to be found. For example, heterochromia iridis (a difference in color of the iris in the two eyes) may be a distinctive feature allowing the diagnosis of Waardenburg syndrome, but telecanthus, that is, lateral displacement of the inner canthi, is seen more frequently (see the discussion later in this chapter and Fig. 5-2).

FIGURE 5-2 In hypertelorism (i.e., wide spacing of the eyes), the interpupillary distance is increased. When the inner canthi are laterally displaced but the interpupillary distance is normal, the eyes falsely appear widely spaced; this feature is called telecanthus. In hypotelorism (not shown), the interpupillary distance is decreased.

Two basic techniques of physical examination

Morphologic physical examinations are approached either qualitatively and descriptively (the “gestalt” technique) or quantitatively and analytically. The qualitative school holds, for example, that the eyes should be described as widely set if they appear so; the quantitative school requires that the distance between such eyes be measured and compared with normal standards.

Describing Visual Observations: Qualitative Versus Quantitative Techniques

The physical examination

Murphy’s law dictates that the infant you most want to examine carefully and completely is also the one who is the most difficult to examine. Sooner or later, you will be called to the neonatal intensive care unit to see a baby suspected of having a “syndrome.” You will find yourself looking down into an incubator at what you can only assume to be a baby, with a stocking cap over the head to prevent heat loss; eyes bandaged to protect against phototherapy lights; nose obscured by a nasogastric tube; mouth filled by an endotracheal tube held in place by several yards of tape; chest covered with monitor electrodes; umbilical artery line in place, one arm taped to an arm board with an intravenous line in place and the other restrained; and the genitalia completely covered by a urine collector. You may be lucky to be able to measure the length of the child’s philtrum!

Key Point

As complete an examination as possible is needed to diagnose the specific nature of a child’s problem, because this is a critical issue in making treatment decisions. For example, deciding that a newborn boy has trisomy 18 may have tremendous relevance in deciding whether he should undergo heroic cardiac surgery.

General Assessment

Examine as much of the child as possible at the time, returning later if necessary. Begin the evaluation with some general assessments of the child, as listed here, and then proceed methodically from the head down to the feet. Much of your examination will be done by means of simple observation and inspection.

General Assessment Questions

1. Note the height, weight, and head circumference. Are they appropriate? Plot measurements on appropriate growth charts.

2. Is one of these measurements discordant with the others?

3. Is the child obese or cachectic?

4. If the child is short, is the short stature proportionate? If not, this anomaly is an instant clue to underlying skeletal dysplasia.

5. If the child’s stature is disproportionate, is the abnormality due to shortening of the limbs or the trunk? Measuring arm span and determining upper-to-lower-segment ratios may help answer this question.

6. If the limbs are short, which portion of the limb is more affected? Achondroplasia, for example, manifests as shortening of the proximal bones of the extremities.

7. Are any asymmetries of body size, shape, or function present? Always compare one side of the body with the other.

8. Observe the child’s posture, responsiveness, and level of activity. Are they appropriate for age?

9. Does the child have an unusual cry?

10. Does the child have an unusual odor? A dysmorphic child may have a metabolic disorder.

Specific Assessments

Head and Face

Key Point

Palpable bony ridges over the suture lines suggest premature craniosynostosis. A large fontanel may be seen in persons with hypothyroidism. A third fontanel is seen in children with Down syndrome. The child with Down syndrome typically has a brachycephalic skull that is round, with a short anteroposterior length and a flat occiput, whereas the child with trisomy 18 typically has a prominent occiput.

Examine the face as a whole, then inspect the individual components. What is the complete gestalt? What aspect of the face is most unusual? Measure the circumference and note the shape of the head. In a child with autism, extreme macrocephaly suggests that testing for a PTEN (phosphatase and tensin homolog) gene mutation should be considered. In the examination of a newborn, molding and edema may make evaluation of the shape difficult, and a second examination may be necessary. Examine the head from different angles to look for asymmetries. Note the size and position of the fontanels as well as the presence of overlapping, ridged, or widely split sutures.

Scalp

The scalp hair pattern is established by the 18th week of gestation and reflects the stretching of the scalp due to underlying brain growth. Abnormal hair patterns suggest prenatally determined underlying abnormalities of the brain. A low posterior hairline may be due to a short or webbed neck and occurs in children with Turner and Noonan syndromes. Scalp defects are seen in persons with trisomy 13. The hair itself may provide a diagnostic clue. It is kinky in persons with Menkes syndrome, coarse in those with mucopolysaccharidoses, sparse in persons with ectodermal dysplasias, and hypopigmented in those with albinism. A white forelock, seen in children with Waardenburg syndrome, calls for a hearing assessment, because affected individuals may experience deafness.

Eyes

Although the eyelids of a newborn frequently are edematous, it is important to examine them carefully. Start with the set of the eyes. Are they deeply set or prominent? Note the size and slant of the palpebral fissures. Is hypotelorism or hypertelorism present? These findings may be part of a total pattern of midline facial maldevelopment that may accompany similar brain abnormalities. Holoprosencephaly may be found with hypotelorism; absence of the corpus callosum may be found on computed tomography scans in a child with hypertelorism. Distinguish hypertelorism from telecanthus (see Fig. 5-2) and from a flat nasal bridge and epicanthal folds. Standards for the normal values for intercanthal and interpupillary distances may be found in various reference sources.

Beyond the lids, look at the globe itself: cornea, iris, lens, sclera, and retina. Do you find normal red reflexes in both eyes? If not, the problem might be (1) corneal clouding, seen in persons with storage diseases, such as the mucopolysaccharidoses; (2) cataracts, which may be found in persons with galactosemia and in a number of different syndromes; or (3) a retinoblastoma, a malignant tumor that can have important genetic implications. The number of potential abnormalities of the eyes, orbits, and periocular region, including those in the eyebrows, lids, and lashes, is enormous; many of them are listed in Table 5-1. An ophthalmology consultation can be very helpful in dysmorphologic diagnosis.

TABLE 5-1 Ocular Findings in Dysmorphology

Feature	Conditions to Watch For
Orbits (the set of the eyes)	Hypotelorism/hypertelorism	Prominent/deeply set eyes
Orbits (the set of the eyes)	Palpebral fissures: size and slant (up, down)	Prominent/flat supraorbital ridges
Eyebrows	High arched	Thick
	Synophrys (eyebrows that meet in the middle)	Thin
	Medial flare	Absent
Eyelashes	Long	Absent
Eyelids	Absent or fused	Ptosis
	Epicanthal folds	Epicanthus inversus
	Telecanthus	Coloboma or dermoid
Globe	Anophthalmia	Microphthalmos
Cornea	Corneal clouding	Microcornea
Lens	Cataract	Dislocated lens
Lens	Stellate pattern	Dislocated lens
Iris	Aniridia	Brushfield spots
	Coloboma	Lisch nodules
	Heterochromia	Lisch nodules
Sclerae	Blue sclerae	Telangiectasis
Retina	Albinism	Optic atrophy
	Pigmentary changes	Coloboma
	Cherry-red spot	Detachment
Motility	Nystagmus	Strabismus

Ears

Because the ear has a complex origin, it is subject to a wide variation in position, size, and structure and is almost as individual as fingerprints. Assessing ear position and rotation often is extremely subjective and imprecise. A scrupulous examination technique is required to conclude that a child has “low-set” ears. The ears must be examined at an appropriate angle. If examined from the front with the child’s neck extended, the ears will appear low. If the ears are examined from the side, assessment of their set is subjectively influenced by its relation to the vertex above and the chin and shoulder below. In infants, in whom the mandible and neck are small in relation to the head, this circumstance often results in an incorrect judgment of low-set ears. The ears also appear low set if (1) the head shape and size are unusual; (2) the helix is poorly developed; (3) the mandible is particularly small; or (4) frequently, no matter the angle from which the ears are examined, they are rotated posteriorly.

The best way to assess the set of the ears is to examine the child from the front, with the child’s head held erect and the eyes facing forward. Then draw an imaginary line between the two inner canthi of the eyes and extend it around the head. The superior attachment of the pinna of the ear should be at or above that line (Fig. 5-3).

FIGURE 5-3 Method for determining the position (set) of the ears.

Next, note the size and shape of the ears. Interestingly, the right ear often is slightly larger than the left ear. Examine the preauricular region carefully for tags, pits, and fistulas (Fig. 5-4). These findings can be important clues to other abnormalities, especially those involving the branchial arches and, often, hearing deficits.

FIGURE 5-4 Ear pits, found in the preauricular region, may be important clues to other abnormalities.

Key Point

Evaluate any patient with malformations involving the external ear for deafness and for kidney and urinary tract abnormalities.

The shape of the ear is often distinctive in various syndromes and should be compared with the photographs in standard reference texts. Examine the earlobe for the anterior diagonal linear creases commonly found in patients with the Beckwith-Wiedemann syndrome. Some authorities allege that such creases are found at a higher frequency in patients with coronary artery disease. Persons with Beckwith-Wiedemann syndrome also have punched-out grooves on the backs of the auricles.

Nose and Mouth

Evaluation of the nose, mouth, palate, tongue, and chin is more subjective. The nasal bridge may be low or prominent, and the tip of the nose may be downturned, flat, broad, bulbous, or narrow. It may even be bifid in cases of frontonasal dysplasia. Many syndromes feature nares that are upturned (anteverted). In the neonate with respiratory distress, always check for choanal atresia.

Examination of the mouth begins with the lips. The philtrum often is flat and featureless in children with fetal alcohol syndrome. Clefts of the upper lip may occur with or without cleft palate and may be unilateral or bilateral. Clefts are rarely seen in the midline, but midline cleft of the lip may be a clue to midline CNS abnormalities, such as holoprosencephaly. Clefts of the lip may extend upward to involve the nostril and may extend through the maxilla.

When evaluating the child with a cleft lip, with or without cleft palate, it is important to examine the lower lips of both the child and the parents for lip pits (Fig. 5-5). The van der Woude syndrome is an autosomal dominant syndrome in which a parent may have only the lip pits but his or her child may have the syndrome’s full expression with clefts of the lip, palate, or both. The parents of such a child face a risk as high as 50% of having another affected child, whereas parents whose child has only an isolated cleft lip have only a 3% to 5% risk of recurrence.

FIGURE 5-5 Lip pits are important physical signs in the evaluation of a family with cleft lip.

Note the size of the mouth and the shape of the lips. Examine the palate for posterior clefts, which are frequently missed. Use palpation and inspection. A V-shaped cleft warrants a search for other anomalies, because it results from fusion arrest of the palatal shelves rather than from interference with closure by the tongue, as seen with a U-shaped cleft. The latter may be observed with micrognathia in the Pierre Robin sequence. Diagnostic possibilities include Sticker syndrome and a chromosome 22q11 deletion, as well as other syndromes. If you note an apparently enlarged tongue, consider whether it is truly large or whether the jaw is small. Is the tongue really large or merely prominent because it is protruding? Remember that the mandible is normally slightly recessed in newborns.

Key Point

The finding of a bifid uvula is important; it represents a subtle form of a cleft palate and may be associated with a submucous cleft of the palate.

Note any gingival hyperplasia or oral frenula and the state of the teeth. Record the presence or absence of teeth, spacing and arrangement, timing of eruption (premature or delayed), size, structure, and color, which may provide clues to the state of the enamel. Consider ectodermal dysplasias in a child whose teeth are delayed in eruption, who has few teeth, or whose teeth are abnormal in shape (e.g., cone-shaped). A single central upper incisor is a sign of holoprosencephaly.

Neck and Chest

Examine the child’s neck for branchial cleft sinuses and cysts, webbing and redundant skin folds, a short neck, and torticollis. Because torticollis often develops as a result of intrauterine crowding, it frequently is associated with congenital hip dislocation.

When examining the chest, note its size—that is, measure the chest circumference and shape, and consider the following questions:

1. Is it small, bell-shaped, or “shieldlike”?

2. Is pectus excavatum or pectus carinatum present?

3. Is the sternum short, as seen in persons with trisomy 18?

4. Are the nipples normally spaced or widely spaced? Normal standards are available for comparison.

5. Are any accessory nipples present? These nipples often are overlooked because they can be found anywhere along the “milk line,” which runs from the normal nipple position down toward the inguinal ligament. In persons with ectodermal dysplasias, the nipples may be absent.

6. Are the clavicles absent or hypoplastic, as in persons with cleidocranial dysostosis?

7. Are any asymmetries present that suggest hypoplasia of the pectoralis muscles, as seen in persons with the Poland syndrome (in which a unilateral defect of the pectoralis muscle accompanies syndactyly of the hand on the same side)?

A thorough cardiac examination is, of course, imperative.

Abdomen

Note whether the abdomen is protuberant or scaphoid. Are there any abdominal wall defects? Distinguish an omphalocele from gastroschisis and from an umbilical hernia. An omphalocele protrudes at the umbilical cord insertion site and is covered only by a sac of amnion. An umbilical hernia protrudes at the same site, but it is covered with skin and subcutaneous tissue. Gastroschisis is a defect in the abdominal wall, not at the umbilical cord insertion site, that occurs as a sporadic isolated defect, whereas an omphalocele carries a high risk of associated anomalies or chromosomal abnormalities. Is any organomegaly present? Are there any unusual masses?

Take a moment to examine the umbilicus and, in the neonate, the cord and its vessels. A short umbilical cord suggests poor fetal movements that have not stretched the cord. Infants with a short umbilical cord should be watched for neurodevelopmental problems. Other anomalies (especially cardiac ones) also should be considered when a single umbilical artery is found. “Contemplating the navel” helps identify the unusual umbilical shapes seen in many syndromes, such as Aarskog, Rieger, and Robinow syndromes.

Back

Examine the back for kyphosis, scoliosis, and lordosis. A neural tube defect may be obvious, but do not neglect subtle abnormalities, such as sacral dimples that may accompany sinuses; hair tufts; and other overlying cutaneous changes such as pigmentation, hemangiomas, and lipomas. Note the position and patency of the anus. An anteriorly placed anus often is associated with constipation.

Ambiguous Genitalia

The parents’ first question upon the birth of their child is often, “Is it a boy or girl?” They expect an immediate, definitive answer. Ambiguity of the genitalia makes this determination difficult (see Chapter 4), and how you handle this issue from the beginning is critical.

Key Point

The finding of ambiguous genitalia constitutes a genetic emergency.

Parents of a child with ambiguous genitalia should be told that their baby was born with genitalia that are not yet fully developed, making it impossible to tell at that moment whether the baby is a girl or a boy. They should be told that studies and consultations will be performed immediately to determine the nature of the problem. It is important that all health care personnel involved with the family be consistent in their counseling and that no one makes “snap” predictions. The parents should be advised to delay the naming and sex assignment of the baby until the necessary tests are completed to allow a firm gender assignment. They should be encouraged to see the baby and examine the genitalia with the physician. Ultimately, consultation with a team that may include an endocrinologist, geneticist, urologist, and plastic surgeon is necessary for appropriate gender assignment and case management. Reassure the parents that whatever the final diagnosis, surgical procedures can be performed to complete the process of development of the genitalia to allow appropriate sexual functioning.

The most important physical finding is the presence or absence of palpable gonads. Gonads that are palpable in the inguinal canal or labioscrotal folds are nearly always testes, and the infant is a biologic male; the possibility of a virilized female is excluded. Any infant with ambiguous genitalia and without palpable gonads must be presumed to be a female with salt-losing congenital adrenal hyperplasia, a potentially life-threatening condition, until proved otherwise.

Next, examine the phallus. If the phallus has a urethral opening at or near the tip, it is more likely to be a penis. The size of the phallus may be important in determining the sex for child rearing purposes. Genital abnormalities range in a spectrum from clitoromegaly in a female infant to hypospadias, micropenis, and cryptorchidism in a male infant.

Abnormalities of the Genitalia in Older Children

Key Point

Abnormalities of the genitalia in older children also are important indications of potential problems. They may signify endocrine (often hypothalamic or pituitary) dysfunction or urinary tract maldevelopment.

A variety of syndromes are associated with genital hypoplasia, including the Prader-Willi and Bardet-Biedl syndromes. An affected male has a micropenis and an underdeveloped scrotum. Scrotal abnormalities may be part of various syndromes, such as the “shawl scrotum” seen in persons with the Aarskog syndrome (in which the scrotum appears bifid, with the scrotal fold extending around the base of the penis in a manner resembling a shawl around the neck). In the female, absence or hypoplasia of the labia minora and hypoplasia of the clitoris may be found. The detection of genital abnormalities should arouse suspicion of urinary tract anomalies.

Limbs

Examination of the limbs is another critical component of the physical examination for abnormalities. Almost 25% of minor anomalies are found in the hands. A good way for the physician to begin limb examination is to count the baby’s fingers and toes. Failure to notice polydactyly can be embarrassing, so look carefully. The extra digit may be on the thumb side (preaxial polydactyly) or on the little finger side (postaxial polydactyly). In some infants with polydactyly, the supernumerary digit can appear only as a tiny nubbin of tissue (inappropriately called a “skin tag”) at the base of the little finger. These nubbins are just as significant as full extra digits with bones. If they have been removed previously (e.g., in the neonatal period by suture ligation), the only evidence of the polydactyly may be the presence of a tiny stellate scar opposite the base of the little finger. Postaxial polydactyly is a relatively common autosomal dominant feature, particularly in black people.

Observe whether the digits are fused (syndactyly), short (brachydactyly), or long and spindly like a spider’s legs (arachnodactyly). Also observe the following:

• Are the digits restricted in their ability to extend (known as camptodactyly), or are they hyperextensible?

• Is the little finger short? It should extend to the distal flexion crease of the fourth finger.

• Does the little finger have a single flexion crease, or is it incurving (known as clinodactyly) (Fig. 5-6)? The incurving fifth finger represents hypoplasia of the middle phalanx, perhaps the most common physical sign associated with chromosomal disorders.

FIGURE 5-6 Incurving of the fifth finger, termed clinodactyly, results from hypoplasia of the middle phalanx. Note that this child with Down syndrome has only a single flexion crease of the fifth finger and a single transverse palmar crease.

Hypoplasia of the nails may be a mild form of limb reduction and is seen in persons with the fetal hydantoin syndrome. Look at the thumbs and observe the following:

• Are the thumbs unusually broad, finger-like or proximally placed, hypoplastic or absent, or triphalangeal?

• When the hand is held in a clenched fist, does the second finger overlap the third finger and the fifth finger overlap the fourth finger? This latter finding is seen in persons with trisomy 18 and occasionally trisomy 13, as well as in persons with the Smith-Lemli-Opitz and Pena-Shokeir syndromes.

• Are any of the metacarpals short? Shortening is apparent as a short knuckle and typically is seen in persons with Turner syndrome and in those with pseudohypoparathyroidism.

• Is there dorsal swelling of the hands or feet? This swelling may be the only sign of Turner syndrome in the neonate, and often it is transient. If this swelling is missed or ignored, a major diagnostic clue may be neglected.

Note the palmar flexion creases (see Fig. 5-6). A single transverse crease or a bridging of the two transverse palmar creases reflects a short palm. A single transverse palmar crease is found unilaterally in 4% of the normal population, bilaterally in 1% of the normal population (twice as often in males as in females), and in about 50% of children with Down syndrome.

A thumb held adducted in the palm, often referred to as a “cortical thumb,” may be a sign of CNS damage from birth asphyxia, but if you observe that a web of skin has formed, tethering the thumb, you can be sure that the defect is prenatal in origin. This finding can have important medicolegal implications.

More formal measurements of the hands and digits and careful analysis of dermatoglyphics can be performed. Although these evaluations are beyond the scope of this chapter, details may be found in dysmorphology reference books.

Dermatoglyphic abnormalities also can be present on the feet. A sandal gap is a wide space between the first two toes that would accommodate an extra digit. A common finding is syndactyly of the second and third toes, which often is a familial trait but also is seen in persons with Smith-Lemli-Opitz syndrome. When examining the feet, look for a prominent calcaneus or “rocker-bottom” foot, which may be seen in persons with trisomy 18, as may many forms of clubfoot.

Note the length and mobility of the limbs:

• Is there joint hypermobility or contracture?

• Are any of the other joints webbed, indicating long-standing contracture?

• Are joint dislocations present?

The wrist and thumb signs are important skeletal features of Marfan syndrome. The wrist sign is present when the thumb overlaps the terminal phalanx of the fifth finger when grasping the other wrist. The thumb sign is said to be present when, with a clenched hand and with the thumb held against the palm with the fingers over it, the entire nail of the thumb projects beyond the ulnar border of the hand.

Other aspects to consider are as follows:

• Are the limbs short? The fingertips should reach to the upper thigh if the upper extremities are of normal length.

• If the limbs are short, is the shortening due to limb reduction defect (i.e., are there congenital amputations) or dwarfism?

• Is disproportion present? If so, which segments are involved?

• Are any bones missing?

Many syndromes feature radial aplasia, hypoplasia, or patellar hypoplasia. Skeletal radiographs often are an important part of the dysmorphology assessment.

Skin

Examine the skin with the child unclothed. You may note diffuse skin changes, such as thin, thick, coarse, elastic, or lax skin, or localized changes such as hemangiomas, nevi, café au lait spots, or hypopigmented macules (see Fig. 4-24). The last two features are among the important cutaneous findings in the phakomatoses, such as neurofibromatosis and tuberous sclerosis. Examination with a Wood ultraviolet lamp, which makes depigmented lesions more obvious, often is helpful. Other abnormalities of pigmentation, ichthyosis, or photosensitivity may be present. Besides the scalp hair and nails, remember that body hair and sweat glands are skin appendages, and they also may be affected in the child with an ectodermal dysplasia. Many cutaneous findings are signs of hereditary syndromes that are associated with a predisposition for malignancies to develop. Readers interested in more detail on skin signs of genetic disorders may read one of several excellent reference works on the genodermatoses.