PREP Answers Week of August 21
1. Correct Answer C
The Ehlers-Danlos syndromes (EDSs) comprise a group of genetic connective tissue disorders that are
characterized by hyperextensibility of skin (Item C186A), hyperextensibility of joints, and poor wound
healing. The classification of EDS is evolving; at one time, it included 11 disorders, but the classification
scheme now has been simplified to include 6 primary types.
Of the different forms of EDS, the most common are the classic type (previously types I and II) and the
hypermobility type (previously type III). In the classic type, the skin is soft and hyperextensible; it often is
described as "the skin you love to feel." Individuals who have the classic type have easy bruising, often with
multiple bruises in various stages of healing, and they have thin, "cigarette paper" scars, as reported for the
boy in the vignette. Individuals who have the hypermobility type have soft skin, although it is typically less
hyperextensible than seen in the classic type, and they have large and small joint hypermobility. Often,
there is a history of recurrent spontaneous dislocation of joints. Scar formation is usually normal. Recent
studies have shown that individuals who have both the classic and hypermobile types are at increased risk
for dilatation or rupture of the ascending aorta.
It is recommended that joint hypermobility be determined using the Beighton criteria. A score of 5/9 or
greater is necessary to diagnose hypermobility using the following maneuvers/observations:
1) Passive dorsiflexion of the 5th fingers beyond 90 degrees from the horizontal plane (1 point for each
hand)
2) Passive apposition of the thumb to the flexor aspect of the forearms (1 point for each hand)
3) Hyperextension of the elbow beyond 10 degrees (1 point for each elbow)
4) Hyperextension of the knee beyond 10 degrees (1 point for each knee)
5) Forward flexion of the trunk with knees fully extended so that the palms of the hand rest flat on the floor
(1 point)
Individuals who have the vascular type of EDS (previously classified as type IV) often have a characteristic
facies that features large, prominent eyes; delicate nose; and thin lips. Skin is translucent, and often the
vasculature can be seen easily, giving the upper chest and trunk a "road map" appearance.
Hyperextensibility is most notable in the small joints, and there is often acrogeria (hands look older than
expected). Individuals who have the vascular type of EDS are at increased risk for spontaneous rupture of
arteries (medium-size), uterus (during pregnancy), and intestine. The remaining types of EDS (eg,
kyphoscoliosis type, arthrochalasia type, and dermatosparaxis type) are far less common than those
previously delineated.
Testing for EDS is not clinically available for most types. Mutations in type V collagen are a major cause of
the classic type of EDS, but such testing remains in the research phase. There is no testing available for the
hypermobility type. Testing for individuals suspected of having the vascular form of EDS is clinically available
and involves analysis of type III collagen synthesis, secretion, or structure on cultured skin fibroblasts.
Additionally, if an abnormality is identified, mutational analysis is available.
The child described in the vignette has diffuse joint hypermobility, unusual scar formation, and
hyperextensible skin, as well as multiple bruises. This constellation of features should make the practitioner
consider the diagnosis of EDS. Although child abuse always should be suspected in a child who has multiple
bruises, and it cannot be ruled out simply because the child has EDS, the physical features described make
EDS the most likely diagnosis. Cutis laxa is a group of connective tissue disorders characterized by
redundant sagging skin, especially over the dorsa of the hands and feet and on the face. The skin is not
hyperextensible and is not fragile. Hemophilia is an X-linked disorder caused by factor VIII deficiency that is
associated with hemarthroses and prolonged bleeding after tooth extraction. Affected individuals do not have
unusual scar formation, ligamentous laxity, or hyperelasticity of the skin. Finally, idiopathic
thrombocytopenic purpura is associated with cutaneous petechiae and purpura but not hyperextensibility of
joints or skin or poor wound healing. PREP 2006 Q 186
2. Correct Answer B
Strabismus is the misalignment of the eyes. Early detection and treatment of this common ocular disorder is
necessary to prevent amblyopia, which is a reduction in central visual acuity due to sensory deprivation. If
proper alignment of the visual axis is restored early, the child who has strabismus is more likely to develop
normal binocular vision.
A variety of tests can be performed to assess visual alignment in children. The most common and easily
performed test is the Hirschberg corneal light reflex test. A light is shined into the child's eye while the child
looks directly at the light source. In normal children, the reflected light appears symmetric and slightly nasal
to each pupil. In children who have strabismus, the reflected light is asymmetric. Another test for strabismus
is the cover test, but this test requires cooperation, normal eye movement capability, and good vision in
both eyes.
Because the child described in the vignette has a normal corneal light reflex, it is unlikely that he has
strabismus. The false appearance of strabismus in a child who has normal alignment of the visual axes is
termed pseudostrabismus (Figure C197A). Children who have flat nasal bridges and epicanthal folds are
more likely to have pseudostrabismus because less white sclera is observed nasally during lateral gaze.
Indeed, parents may state that the eye almost disappears from view during lateral gaze. Pseudostrabismus
usually resolves as the child grows, the nasal bridge becomes more prominent, and the epicanthal folds
diminish. There is no need to refer this child to a geneticist, ophthalmologist, or neurologist, and further
examination under general anesthesia is unnecessary.PREP 2005 Q 197
3. Correct Answer E
The National Cholesterol Education Program (NCEP) specifies children who should be screened for
hypercholesterolemia and makes recommendations for diet and drug treatment of children who have varying
degrees of elevated serum lipids. Selective screening for hyperlipidemia is recommended over universal
pediatric screening. Primary care practitioners have the option to screen any child, however, if the parents
request the screening. Parental hypercholesterolemia (total cholesterol of >240 mg/dL [6.2 mmol/L]) in
either parent should prompt screening via a nonfasting total blood cholesterol measurement in children. If
the total cholesterol is between 170 and 199 mg/dL [4.4 and 5.1 mmol/L], as described for the boy in the
vignette, a repeat total cholesterol profile should be obtained. The repeat total cholesterol measurement
does not require fasting.
If the repeat total cholesterol is in the same range or greater, a fasting lipoprotein analysis is performed. A
fasting lipoprotein analysis should be performed without the repeat total cholesterol if the first screening
total cholesterol is 200 mg/dL [5.2 mmol/L] or greater. The NCEP decision tree (Figure C167A) recommends
repeat lipoprotein analysis in 5 years for low-density lipoprotein (LDL) cholesterol values in the acceptable
range (<110 mg/dL [2.8 mmol/L]). For intermediate LDL cholesterol values (110 to 129 mg/dL [2.8 to 3.3
mmol/L]), a repeat analysis is recommended and an American Heart Association Step I diet is initiated if
that range is confirmed. High LDL cholesterol values (>130 mg/dL [3.4 mmol/L]) also require confirmation
with repeat testing, but they are grounds for starting a Step I and probably within 6 months a Step II diet
unless an LDL cholesterol level of less than 130 mg/dL (3.7 mmol/L) (preferably <110 mg/dL [2.8 mmol/L])
is reached.
The Step I diet contains no more than 30% of total calories as total fat and less than 10% of total calories as
saturated fatty acids. Polyunsaturated fatty acids comprise up to 10% of total calories, with the remaining
fat as monounsaturated fatty acids. Dietary cholesterol is limited to 300 mg/d. In the Step II diet, less than
7% of total calories come from saturated fatty acids, and only 200 mg/d of dietary cholesterol is allowed.
Premature cardiovascular disease in a parent or grandparent is an indication for bypassing the requirement
for baseline screening with a total cholesterol measurement and screening instead with a fasting lipid profile.
Parents or grandparents in whom coronary atherosclerosis or vascular disease was diagnosed before age 55
years include those who have angina, myocardial infarction, cerebrovascular disease, peripheral vascular
disease, and sudden cardiac death or who have undergone balloon angioplasty or coronary bypass surgery.
Some experts believe the age limit for premature cardiovascular disease should be set higher for female
relatives.
The total cholesterol level of the boy described in the vignette is not sufficiently high to prompt immediate
measurement of a fasting lipid profile, although some physicians may proceed to this step. The choice of a
diet with less than 7% saturated fat (the Step II diet) is not indicated unless the Step I diet has failed to
bring the LDL cholesterol value into an acceptable range. The choice of a diet with less than 300 mg/d
dietary cholesterol (Step I diet) is not appropriate unless the LDL cholesterol is elevated. Treatment with bile
acid sequestrants is recommended as first-line drug therapy for diet-refractory elevated LDL cholesterol in
some children, but it is clearly not the best choice for the child in the vignette. PREP 2004 Q 167
4. Correct Answer D
Ingestion of more than 50 to 60 mg/kg of elemental iron is likely to produce symptoms of toxicity. Toxicity
from iron poisoning is one of the most common potentially fatal ingestions in children. Excess free iron is
believed to act as a mitochondrial poison, leading to the production of a metabolic acidosis. There is also a
direct caustic effect on the mucosa of the gastrointestinal tract that can lead to hemorrhagic necrosis. The
child described in the vignette has ingested an amount of iron that is highly likely to lead to toxicity and
should be managed as such.
Iron overdose can be divided into four phases. The first phase is characterized by vomiting, diarrhea, and
gastrointestinal (GI) blood loss from the direct mucosal injury and lasts up to 6 hours after the ingestion. In
the second phase, which can last from 6 to 24 hours postingestion, the GI symptoms appear to abate. In
severe overdoses, this remission is only temporary and is followed by the cyanosis, severe metabolic
acidosis, coma, seizures, and shock characteristic of the third phase. Survivors of severe iron poisoning can
develop late stricture formation or pyloric stenosis in the fourth phase.
GI decontamination using normal saline lavage or whole bowel irrigation may be of benefit if the child
presents shortly after significant iron ingestion. Patients who have a history suggestive of severe iron
overdose also should receive abdominal radiographs to evaluate for radiopaque material. All patients who
present after iron ingestion should have blood drawn for a complete blood count and measurement of
electrolytes. An iron level should be measured 3 to 5 hours after ingestion.
A white blood cell count of greater than 15 x 103/mcL (15 x 109/L) or serum glucose greater than 150 mg/dL
(8.3 mmol/L) is predictive but not sensitive for elevated serum iron levels. Serum iron levels measured 3 to
5 hours after ingestion correlate with the likelihood of developing symptoms: a level of less than 350 mcg/dL
(62.7 mcmol/L) generally predicts an asymptomatic course, a level of 350 to 500 mcg/dL (62.7 to 89.5
mcmol/L) predicts mild phase 1 symptoms, and levels higher than 500 mcg/dL (89.5 mcmol/L) suggest a
high risk for the development of severe toxicity. Measurement of total iron-binding capacity no longer is
recommended.
If a child is symptomatic in the first 6 hours postingestion, has positive radiographs, or has an iron level
higher than 500 mcg/dL (89.5 mcmol/L), iron chelation therapy with parenteral deferoxamine should be
initiated. If results of screening laboratory tests and radiographs are normal and the child remains
asymptomatic, he or she may be discharged home after a 6-hour observation period. PREP 2005 Q 165
5. Correct Answer E
Physiologic breast hypertrophy in the neonate results from the influence of maternal estrogens during the
first few postnatal weeks. Often discovered as a painless palpable mass beneath the nipple, physiologic
breast hypertrophy is a normal variant in term neonates of both genders. Swelling of the external genitalia
in newborn girls also reflects stimulation by maternal estrogens. The labia majora may appear full and puffy,
with the thickened labia minora protruding between them. In addition, the vaginal mucosa is pink and moist,
and a milky white discharge (physiologic leukorrhea) may be noted. Vaginal bleeding during the first few
weeks after birth also commonly occurs as maternal estrogen levels fall.
Because it is a normal and often transient physiologic response, reassurance is most appropriate for the
parents of the infant described in the vignette. An infant who has physiologic breast hypertrophy does not
require laboratory evaluation or any procedures to investigate its cause. Invasive procedures such as
excisional biopsy and fine-needle aspiration of the mass are contraindicated because they can cause longterm sequelae by damaging the breast bud. Intramuscular gonadotropin-releasing hormone is unnecessary
because the breast hypertrophy is not related to precocious puberty. Because there is no evidence of
infection on physical examination of the breast bud in the infant described in the vignette, oral cephalexin
also is not indicated. PREP 2004 Q 13