Pediatric Examination and Board Review (146 page)

6.
(D)
Neural tube defects occur with an incidence of about 1 in 1000 live births. Most cases are inherited in a polygenic or multifactorial pattern with both genetic and environmental factors contributing to the increased recurrence risk. The risk of recurrence after one affected child rises to 3-4% and increases to approximately 10% with two previous abnormal pregnancies. Periconceptional use of folic acid supplementation has been shown to decrease the risk of neural tube defects. Folic acid should be started 1 month before conception and continued until at least 12 weeks of gestation. All women considering pregnancy should take 0.4 mg folic acid daily, and women who have previously had a pregnancy with a neural tube defect should take 4 mg folic acid daily.

7.
(E)
All can be seen with amniotic bands. The bands can become adherent to any part of the fetal body and impair vascular supply or interfere with normal tissue growth leading to a variety of malformations. The bands can be swallowed and lead to major disruption of normal tissue growth and clefts of the face.

8.
(A)
All definitions are correct except for “association.” See answer 10 for definition of association.

9.
(A)
Several craniosynostosis syndromes are characterized by the facial findings described and occur secondary to bilateral coronal synostosis. In addition to craniosynostosis, there can be other findings such as syndactyly of digits as seen in Apert syndrome, large thumbs and first toes seen in Pfeiffer syndrome, proptosis seen in Crouzon syndrome, and ear malformations seen in Saethre-Chotzen syndrome. Craniosynostosis can be isolated and sporadic, but a careful examination must be done to look for the other associated malformations.

10.
(E)
An association is the nonrandom occurrence of multiple anomalies without a known developmental field defect, sequence initiator, or causal relationship. The clustering occurs at such a frequency that the malformations have a statistically significant rate of simultaneous connection. VATER association:
V
ertebral anomalies,
A
nal anomalies,
T
racheo
e
sophageal fistula,
R
enal or
R
adial anomalies.

11.
(A)
CHARGE association:
C
oloboma of the eye,
H
eart defects,
A
tresia of the choanae,
R
etardation of growth and development,
G
enital anomalies,
E
ar anomalies. DiGeorge syndrome is characterized by conotruncal heart defects, immune deficiency, and hypoparathyroidism. MURCS association:
Mü
llerian duct aplasia,
R
enal aplasia,
C
ervicothoracic
S
omite dysplasia. Poland anomaly is characterized by unilateral defect of the pectoralis muscle and syndactyly of the hand.

12.
(D)
The features listed are those associated with severe oligohydramnios and are commonly referred to as the Potter facies or syndrome. Normal fetal lung development depends on the normal production and inhalation of amniotic fluid, and in the absence of amniotic fluid, significant pulmonary hypoplasia occurs. This is the cause of death in many affected individuals. The underlying mechanism can be renal agenesis or renal dysplasia, and these complications should be investigated in any child with the Potter facies. Additional causes include bladder outlet obstruction or prolonged premature rupture of the membranes.

13.
(B)
Beckwith-Wiedemann syndrome is an overgrowth condition that is a complex multigenic disorder caused by alterations in growth regulatory genes on chromosome 11p15. Clinical features include macrosomia, hemihyperplasia, macroglossia, abdominal wall defects, embryonal tumors, adrenocortical cytomegaly, ear anomalies, visceromegaly, renal abnormalities, and neonatal hypoglycemia. Children with Beckwith-Wiedemann have an increased risk for cancer (estimated to be 7.5%). The 2 most common tumors are Wilms’ tumor and hepatoblastoma. Screening includes abdominal ultrasounds every 3 months until 8 years of age for Wilms’ tumor and AFP for the first few years as a marker for hepatoblastoma. AFP levels tend to be higher in children with Beckwith-Wiedemann in the first year of life. Calcium levels are typically normal in Beckwith-Wiedemann syndrome but may be abnormal in Williams syndrome and 22q deletion. GH is not appropriate because this is an overgrowth condition, and there is not an increased incidence of seizures. Structural cardiac abnormalities occur in 9-34%. Cardiomyopathy has been rarely reported, and cardiomegaly of early infancy usually resolves spontaneously.

14.
(D)
Prader-Willi syndrome is a result of genetic abnormalities involving an imprinting region on the long arm of chromosome 15. In addition to the features listed, affected individuals typically have infantile central hypotonia and feeding difficulties with failure to thrive, rapid weight gain between 1 and 6 years, developmental delays and mental retardation, hypopigmentation, thick viscous saliva, skin picking, and a high pain threshold. Angelman syndrome is characterized by microcephaly, seizures, ataxia, and severe mental retardation. Beckwith-Wiedemann was discussed in question 13; Bardet-Biedl and Sotos syndromes are both overgrowth syndromes. Bardet-Biedl is characterized by polydactyly, retinitis pigmentosa, hypertension, truncal obesity, and developmental delay. Sotos syndrome is characterized by growth greater than the 97th centile, significant macrocephaly, developmental delay, and characteristic facial features.

15.
(D)
Velocardiofacial syndrome and DiGeorge syndrome were thought to be clinically distinct syndromes that are now both known to be a result of a microdeletion of 22q11. The common clinical features of this microdeletion include conotruncal heart defects in 70% of patients (TOF, interrupted aortic arch, VSD, truncus arteriosus, vascular ring, ASD, aortic arch anomaly); feeding difficulties in 30%; immune dysfunction in 70% (impaired T-cell production and function, immunoglobulin [Ig]A deficiency); hypoparathyroidism leading to hypocalcemia in 50%; palate abnormalities in 70% (velopharyngeal incompetence [VPI], submucosal or overt cleft palate, bifid uvula, cleft lip/palate); developmental delays and psychiatric abnormalities; growth failure. A transverse palmar crease is a sign of Down syndrome.

16.
(B)
Microdeletion syndromes are caused by deletions of relatively large segments of the genome, 1-3 megabases (Mb) of DNA, which affect multiple genes. The resolution of routine cytogenetics is 3-5 Mb of DNA so these microdeletions are not readily detected by routine methods. FISH is a molecular cytogenetic method that combines DNA probes and fluorescence methods to identify specific regions of chromosomes. Each microdeletion syndrome always involves the same region of a specific chromosome, and probes directed at these regions can be used to detect the deletions. The syndromes are suspected based on specific clinical features, and then FISH with a probe specific for that syndrome can be ordered/done. Sequencing is used to determine the exact sequence of DNA and to detect single base pair mutations. PCR is a molecular technique that allows amplification of discrete fragments of DNA and is used in many diagnostic tests.

S
UGGESTED
R
EADING

Aase JM.
Diagnostic Dysmorphology
. New York, NY: Plenum Medical; 1990.

Jones KL.
Smith’s Recognizable Patterns of Human Malformation.
6th ed. Philadelphia, PA: WB Saunders; 2005.

CASE 86: A 6-MONTH-OLD BOY WITH SHORT STATURE SUGGESTIVE OF SKELETAL DYSPLASIA

A 6-month-old boy comes for evaluation of short stature. The history shows that the child was born after an uncomplicated pregnancy and delivery. He has been well with no medical complications or hospitalizations. The parents do not remember that anyone was concerned about his size at birth, but they noted shortly thereafter that he was not growing as they expected and they felt that he has short extremities. They also report that recently he has been snoring more at night and has loud breathing during the daytime.

On physical examination, growth parameters show height 60 cm (<5th percentile), head circumference 46 cm (>95th percentile). You note macrocephaly, frontal bossing, flat nasal bridge, hypoplasia of the maxilla, rhizomelic shortening of the extremities, lumbar lordosis, and short hands and feet.

SELECT THE ONE BEST ANSWER

1.
Based on the clinical features the most likely diagnosis is

(A) achondroplasia

(B) growth hormone deficiency

(C) hypochondroplasia

(D) osteogenesis imperfecta (OI)

(E) Turner syndrome

2.
Evaluations that could be helpful in establishing the diagnosis might include

(A) bone age

(B) CT scan of brain

(C) renal ultrasound

(D) skeletal survey

(E) vertebral radiographs

3.
The child is confirmed to have achondroplasia. What are potential medical complications that need to be addressed in this child?

(A) congenital heart defects

(B) diabetes mellitus

(C) fatty liver

(D) obstructive or central sleep apnea

(E) renal malformations

4.
In regard to the history of the snoring and breathing issues reported, what evaluations should be considered?

(A) counseling regarding weight control

(B) evaluation for possible tonsillectomy

(C) magnetic resonance imaging (MRI) scan of the brainstem

(D) sleep study

(E) all of the above

5.
How should a person who has achondroplasia be counseled about the chance of having an affected child?

(A) achondroplasia is an autosomal dominant condition with 50% chance of an affected offspring