Pediatric Examination and Board Review (141 page)

(A) chest radiograph

(B) echocardiogram

(C) head ultrasound

(D) renal ultrasound

(E) upper gastrointestinal (GI) series

4.
A karyotype to determine the chromosomal basis of Down syndrome is essential for which of the following reasons?

(A) confirming the diagnosis because the clinical features of Down syndrome can be difficult to recognize in some newborns and can overlap with other conditions

(B) allows appropriate counseling regarding recurrence risks for the parents

(C) helpful in assigning gender in a child with Down syndrome

(D) A and C

(E) none of the above; karyotype is not essential in the evaluation for a child with Down syndrome

5.
Results of chromosome analysis show an unbalanced Robertsonian translocation between the long arm of chromosome 14 and 21: 46, XY, der,(14;21) (q10;q10). Part of the family counseling should include which of the following with regard to this chromosomal rearrangement?

(A) parents should be offered chromosome analysis to see if they are carriers of a balanced Robertsonian translocation

(B) advice not to have any more children

(C) counseling that this is not really Down syndrome because that only applies to trisomy 21

(D) prognostic information that children with unbalanced Robertsonian translocations as the cause of Down syndrome are less severely affected

(E) none of the above

6.
All of the following are associated medical problems in children with Down syndrome except

(A) atlantoaxial instability

(B) hearing loss

(C) polycystic kidneys

(D) sleep apnea

(E) strabismus

7.
Which of the following best describes the expected intelligence and personality of a child with Down syndrome?

(A) all have severe mental retardation with an IQ in the range of 30-40

(B) IQ range of 35-65 with a mean of 54, and occasionally higher

(C) aggressive and violent; prefers to be alone and has little social interaction

(D) affectionate and docile, tends toward mimicry, enjoys music, and has a good sense of rhythm but poor coordination

(E) B and D

8.
The most common cause of trisomy 21 is

(A) maternal nondisjunction at meiosis I with increasing risk associated with advanced maternal age

(B) nondisjunction associated with advanced paternal age

(C) mosaicism

(D) sporadic events unrelated to maternal age

(E) environmental exposure

9.
What is the overall recurrence risk for Down syndrome because of trisomy 21 (as opposed to an unbalanced translocation)?

(A) 1% in women younger than 40 years of age and age-related risk for women older than 40 years of age

(B) age-related risk

(C) 10% in women younger than 35 and agerelated risk in women older than 35

(D) the same as the population risk

(E) none of the above

10.
Which of the following are features of trisomy 13?

(A) micro-ophthalmia, cleft lip and palate, polydactyly, holoprosencephaly

(B) up-slanting palpebral fissures, epicanthal folds, clinodactyly

(C) hypotonia, rocker bottom feet, clenched hand, low-set malformed ears

(D) obesity, hypogenitalism, almond-shaped eyes, small hands and feet

(E) supravalvular aortic stenosis, hypercalcemia, short stature

11.
All of the following are features of trisomy 18 except

(A) cardiac defect

(B) clenched hand

(C) hypoplastic nails

(D) protruding tongue, large cheeks

(E) small palpebral fissures

12.
Which of the following modalities can be used for screening/testing for Down syndrome?

(A) amniocentesis

(B) chorionic villus sampling (CVS)

(C) maternal serum screening

(D) prenatal ultrasonography

(E) all of the above

13.
A newborn is evaluated in the nursery. Pregnancy was complicated by a prenatal ultrasound that showed coarctation of the aorta. This female infant was delivered at term by normal spontaneous vaginal delivery. On physical examination the baby is noted to have lymphedema of the feet and hands, webbed neck, and shield chest. The most likely diagnosis to explain the features is

(A) DiGeorge syndrome

(B) Down syndrome

(C) Klinefelter syndrome

(D) Turner syndrome

(E) Williams syndrome

14.
Which of the following medical problems are
not
associated with Turner syndrome?

(A) agenesis of the corpus callosum

(B) coarctation of the aorta

(C) horseshoe kidney

(D) hypothyroidism

(E) premature gonadal failure

15.
Standard treatment of growth failure in Turner syndrome includes

(A) estrogen replacement

(B) leg-lengthening procedures

(C) maximizing caloric intake

(D) recombinant human growth hormone

(E) none of the above

16.
Which of the following is true regarding Noonan syndrome?

(A) Noonan affects only males

(B) Noonan syndrome is the result of a sex chromosome abnormality

(C) the clinical features of Noonan syndrome have significant overlap with those of Turner syndrome

(D) Noonan syndrome is not a genetic condition

(E) none of the above

17.
An 8-year-old boy is noted to be tall, to have gynecomastia, underdeveloped secondary sexual characteristics, and small testes. The most likely diagnosis is

(A) Noonan syndrome

(B) Marfan syndrome

(C) Klinefelter syndrome (47,XXY)

(D) 47,XYY

(E) mosaic trisomy 8

18.
A newborn with tetralogy of Fallot (TOF) with pulmonary atresia has a normal karyotype by chromosome analysis. Additional genetic testing should include

(A) fluorescent in situ hybridization (FISH) for DiGeorge syndrome

(B) FISH for Down syndrome

(C) FISH for Williams syndrome

(D) high-resolution karyotype

(E) microarray analysis

ANSWERS

1.
(A)
The features described are most consistent with Down syndrome or trisomy 21. Edward syndrome or trisomy 13 is characterized by polydactyly, holoprosencephaly, and cleft lip and palate in addition to many other congenital birth defects. Holt-Oram is associated with congenital heart defect, most often atrial septal defect (ASD) or ventricular septal defect (VSD), and upper limb abnormalities. Patau syndrome or trisomy 18 is associated with clenched hands, feeble activity, weak cry, rocker bottom feet, and many other congenital birth defects. Treacher Collins syndrome, also known as mandibulofacial dysostosis, is associated with defects of the lower eyelids, mandibular and malar hypoplasia, microtia and dysplastic ears, and hearing loss.

2.
(D)
Common newborn features of Down syndrome include those in the answer to question 1 and mild microcephaly, flat occiput, brachycephaly, upslanting palpebral fissures, epicanthal folds, Brushfield spots, protruding tongue, low flat nasal bridge, clinodactyly of the 5th digit, transverse palmar crease, and short stature. Rocker bottom feet are common features of trisomy 18.

3.
(B)
The only investigation listed that should be done in all individuals with Down syndrome is an echocardiogram. Congenital heart defects are present in 40-45% and not all are recognizable by physical examination (thus the need for an echocardiogram). Additional problems that should be remembered in the newborn period but do not necessarily require screening if there are no associated symptoms including intestinal abnormalities such as esophageal or duodenal atresia, or Hirschsprung disease. The incidence of renal malformations in Down syndrome is not significantly higher than the general population risk. Brain malformations such as holoprosencephaly and vertebral anomalies are common in trisomy 13 and 18 but not in Down syndrome.

4.
(D)
Karyotype is helpful in confirming the clinical suspicion especially in premature newborns. The most important reason, however, is for counseling regarding recurrence risks. Trisomy 21 has a low recurrence risk (either based on maternal age or 1%, whichever is higher), whereas an unbalanced translocation may be inherited from a balanced translocation carrier parent and the recurrence risk may be as high as 100% depending on the translocation.

5.
(A)
Robertsonian translocations involve acrocentric chromosomes (the acrocentric chromosomes are 13, 14, 15, 21, 22). Unbalanced rearrangements that include chromosome 21 account for 3.3% of all cases of Down syndrome. One-third of these cases are inherited from a parent with a balanced translocation and two-thirds are de novo events in the infant. The term
Down syndrome
applies to individuals with the recognizable clinical phenotype described and does not imply a specific genetic mechanism. There is no clinical distinction between patients with trisomy 21 (3 full copies of chromosome 21) and translocation cases.

6.
(C)
About 60-80% of children with Down syndrome have hearing deficits. Eye problems may include cataracts, strabismus, myopia, and so on. Fifteen percent will have atlantoaxial instability; although most are asymptomatic, 1-2% will require surgical correction. Other skeletal problems include patella and hip dislocation. Other medical problems in addition to those listed in the answer to question 3 include nutrition (failure to thrive in infancy and obesity in older children and adults), leukemia, seizure disorders, sleep apnea, delayed eruption of teeth, and Alzheimer disease.

7.
(E)
Intelligence is variable and cannot be readily predicted by any reliable factor. Research has shown that early intervention, environmental enrichment, and assistance to the families will result in progress that is usually not achieved by those children who have not had such educational and stimulating experiences. Intelligence deteriorates in adulthood, with clinical and pathologic findings consistent with advanced Alzheimer disease. Although most children and adults have the friendly, docile personality described, 13% have serious emotional problems including depression.

8.
(A)
Most cases of Down syndrome involve nondisjunction of maternal meiosis I, which may be related to the time from meiotic arrest between oocyte development in the fetus and ovulation. There is an increased risk for nondisjunction associated with advancing maternal age (maternal age 30: 1:1000 risk of Down syndrome; age 35: 1:365 risk; age 40: 1:100 risk; age 45: 1:50 risk). The risk is for nondisjunction of any chromosome, but trisomy 13, 21, and 18 are the only trisomies that can result in live born children; the rest tend to result in miscarriage. There is no association between Down syndrome and environmental exposures in the mother. There is no proven increased risk for trisomy with advanced paternal age, but there is an increased risk of new mutation in advanced paternal age. Mosaicism refers to the finding of two different cell lines in an individual. There are individuals with mosaic Down syndrome, meaning they have some cells with trisomy 21 and some cell lines with normal chromosome number. Mosaicism may be associated with a milder phenotype.