Pediatric Examination and Board Review (147 page)

(B) achondroplasia is an autosomal recessive condition with 25% chance of an affected offspring

(C) achondroplasia is an X-linked condition and only affects females

(D) there is no chance for a second affected offspring

(E) the chance of another affected offspring is very low

6.
Multiple genetic conditions are associated with short stature and growth failure. Which of the following syndromes does not have short stature as a major feature?

(A) Cornelia de Lange syndrome

(B) Marfan syndrome

(C) Russell Silver syndrome

(D) Turner syndrome

(E) Williams syndrome

7.
The skeletal survey on a child with short stature shows microcephaly, oval-shaped and hook-shaped vertebral bodies on the lateral view of the spine, wide iliac flare, irregular diaphyseal modeling, metaphyseal widening, all features of dysostosis multiplex. The most likely diagnosis is

(A) Down syndrome

(B) growth hormone deficiency

(C) a mucopolysaccharidosis (MPS)

(D) nutritional rickets

(E) warfarin embryopathy

8.
Clinical features of MPS include all of the following except

(A) coarse facial features

(B) developmental delay and/or mental retardation

(C) hepatomegaly or splenomegaly

(D) structural heart defects associated with hypoxia

(E) restricted joint mobility

9.
If an MPS disease is suspected, which of the following investigations should be considered in pursuing the diagnosis?

(A) enzyme analysis

(B) skeletal survey

(C) urine screening for glycosaminoglycan excretion

(D) A, B, and C

(E) none of the above

10.
MPS occurs by which of the following inheritance patterns?

(A) autosomal dominant inheritance

(B) autosomal recessive inheritance

(C) X-linked inheritance

(D) A and B

(E) B and C

11.
A newborn is noted to have a short forearm or radial ray defect. Further investigations for associated anomalies might include all of the following except

(A) echocardiogram

(B) MRI of the brain

(C) renal ultrasound

(D) upper GI series

(E) vertebral radiographs

12.
The differential diagnosis for the child in question 11 would include

(A) Fanconi syndrome

(B) Holt-Orom syndrome

(C) VATER association

(D) A and C

(E) A, B, and C

13.
What are the recommendations regarding evaluation of an individual with Down syndrome with respect to participation in sports?

(A) no specific precautions are needed

(B) individuals with Down syndrome should be restricted from all sports activities

(C) lateral cervical radiographs in the neutral, flexed, and extended position in children 3-5 years of age

(D) routine blood counts

(E) none of the above

14.
A child presents with blue sclera, multiple fractures from minimal trauma, bowing of the lower limbs, and opalescent dentin (dentinogenesis imperfecta). The most likely diagnosis is

(A) achondroplasia

(B) Ellis-van Creveld syndrome

(C) MPS

(D) OI

(E) none of the above

15.
Which of the following do not correctly describe the clinical features associated with the specific subtype of OI?

(A) OI type I: Few fractures at birth, deformities of the limbs, mild short stature, dentinogenesis imperfecta, and generalized osteopenia

(B) OI type II: Low birthweight and length, crumpled long bones, beaded ribs, soft skull, extremely short, bent, deformed long bones, and early lethality

(C) OI type III: Newborn or young infant with mild bowing of extremities, mild scoliosis, and no effect on final height

(D) A, B, and C

(E) none are correct

16.
Which of the following medical complications is common in OI type I?

(A) cleft lip and palate

(B) congenital heart defect

(C) duodenal atresia

(D) hearing loss

(E) renal abnormality

ANSWERS

1.
(A)
Achondroplasia is characterized by abnormal bone growth that results in short stature with disproportionately short arms and legs, a large head, and characteristic facial features. The clinical features include short stature, rhizomelic (proximal) shortening of the arms and legs with redundant skin folds on limbs, limitation of elbow extension, trident configuration of the hands, genu varum (bow legs), thoracolumbar gibbus in infancy, exaggerated lumbar lordosis, which develops when walking begins, large head with frontal bossing, and midface hypoplasia. Turner syndrome is characterized by short stature but not by macrocephaly or the other clinical features noted. Hypochondroplasia is very similar to achondroplasia but is typically less severe and does not have the facial features listed. OI is a disease characterized by bone fractures.

2.
(D)
A skeletal survey may show findings characteristic of achondroplasia including narrowing of the interpediculate distance of the caudal spine, notchlike sacroiliac groove, and circumflex or chevron seat on the metaphysis. Achondroplasia is a result of mutations in the
FGFR3
gene on chromosome 4p. The common mutation, Gly380Arg, accounts for 98% of all cases. There may be hydrocephalus detected by a CT scan, but that finding would be nonspecific and not lead to the final diagnosis. Similarly findings of vertebral anomalies alone would not be enough to make the correct diagnosis. There is no increased risk of renal malformations in achondroplasia.

3.
(D)
Sleep apnea may be obstructive or central secondary to craniocervical junction cord compression. The other choices are not common problems in achondroplasia. The best predictors of the need for suboccipital decompression include lower-limb hyperreflexia or clonus, central hypopnea demonstrated by polysomnography, and decreased foramen magnum size, determined by CT examination of the craniocervical junction. Additional problems include spinal stenosis and obesity.

4.
(E)
As many as 7.5% of infants with achondroplasia die in the first year of life from obstructive or central apnea. Obstructive apnea may result from midface hypoplasia. Brainstem compression is common and may cause abnormal respiratory function, including central apnea. In one study, 10% of infants had craniocervical junction compression with abnormality of the cervical spinal cord. All children undergoing surgical decompression of the craniocervical junction show marked improvement of neurologic function.

5.
(A)
Achondroplasia is an autosomal dominant disease with only one copy of the
FGFR3
allele being mutated. Thus there is a 50% chance of passing on the mutated allele.

6.
(B)
Marfan syndrome occurs in individuals who are taller than expected for their family. Cornelia de Lange is a relatively common syndrome with growth failure, feeding problems, limb defects, and characteristic facial features including round face and synophrys. Russell Silver syndrome is characterized by proportional short statue with preserved head circumference. Turner syndrome is a chromosome anomaly among girls that causes ovarian failure in addition to short stature. Williams syndrome is associated with supravalvular aortic stenosis, hypercalcemia, and friendly personality.

7.
(C)
The term
dysostosis multiplex
refers to the specific skeletal findings mentioned, and they are specific in the sense that their presence indicates an abnormality of complex carbohydrate degradation or lysosomal transport. The intralysosomal accumulation of partially degraded complex carbohydrates results in a variety of disorders, which, depending on the type of stored material, have been classified as mucopolysaccharidoses, oligosaccharidoses, and glycoproteinosis. The finding of dysostosis multiplex is specific for one of these classes of disorders but not diagnostic of a specific one.

8.
(D)
The clinical features of MPS have significant overlap, although there are distinct variations within the different subtypes. The general features that should raise suspicion about MPS include those listed as well as microcephaly, corneal opacities, and mental retardation. The age of onset of developmental issues including neurodegeneration varies from the newborn period to several years of age. There can also be short stature, progressive joint contractures, and heart disease (valvular disease and cardiomyopathy but not structural lesions causing hypoxia).

9.
(D)
When MPS is suspected on a clinical basis, a skeletal survey to look for the presence of dysostosis can be helpful. Dysostosis is specific for MPS as a class of disease but is not specific for a particular subtype. Urine screening tests to look for excretion of glycosaminoglycans can be helpful but are not always diagnostic and can sometimes be normal even though the patient has a form of MPS. Finally, specific enzyme analysis is available for the different subtypes of MPS and can be tested on blood and/or skin fibroblasts depending on the specific subtype in question.

10.
(E)
Like most metabolic diseases, the vast majority of cases of MPS are inherited in an autosomal recessive fashion. When a child is newly diagnosed, the family should be counseled that the parents are carriers of a gene mutation, and their chance of recurrence for future offspring is 25% for each pregnancy. An exception with regard to MPS is type II (Hunter syndrome), which is X-linked and mostly affects boys; females may be asymptomatic carriers.

11.
(B)
Limb malformations including radial ray anomalies and short limbs can be associated with vertebral anomalies, imperforate anus, cardiac defects, tracheoesophageal fistula (T-E fistula), and renal malformations. Brain malformations are less common and should only be looked for if there is a specific indication to do so based on clinical findings.

12.
(E)
The VATER association is an acronym for vertebral anomalies, anal anomalies, T-E fistula, and renal anomalies. Affected individuals may also have cardiac defects and limb anomalies. Fanconi pancytopenia syndrome should be considered in any patient where VATER is being entertained. Holt-Orom syndrome is characterized by ASD and limb defects but could be distinguished from the other choices if any other complex birth defects were found.

13.
(C)
The current recommendations include screening as indicated in answer C. Children with borderline findings or abnormal films should be evaluated with a careful neurologic examination to rule out spinal cord compression. Neuroimaging (CT or MRI) is probably indicated. Significant changes in a child’s neurologic status would necessitate evaluation and possible treatment. Asymptomatic children with instability (5-7 mm) should be managed conservatively, with restriction only in those activities that pose a risk for cervical spine injury. Contact sports, such as football, wrestling, rugby, boxing, and recreational activities such as trampolining, gymnastics (tumbling), and diving, which require significant flexion of the neck, would best be avoided. It is unnecessary to restrict all activities.