Genetics

A small-for-gestation age and dysmorphic newborn infant with microcephaly and Sloping forehead, cutis aplasia (missing Portion of the skin and hair) of the scalp, polydactyly, microphthalmia, and omphalocele is likely to have which of the following:
A. Holt-Oram syndrome
B. Turner syndrome
C. Edwards syndrome (trisomy 18)
D. Patau syndrome (trisomy 13)
E. Down syndrome (trisomy 21)

D. The appearance of cutis aplasia and polydactyly strongly sug¬gests trisomy 13. Other common features include holoprosen¬cephaly, cleft lip/palate, postaxial polydactyly, flexed and overlap¬ping fingers, coloboma, and cardiac defects (ventricular septal defect, atrial septal defect, patent ductus arteriosus, dextrocardia).

A 2-month-old child was born in a rural hospital. At the time of birth, she was noted to have distinctive facies with microcephaly, ptosis, a beaked nose, and a low-lying philtrum. Her extremities are notable for broad thumbs and large toes. The family is not sure what evaluation was done, but they report they were told everything was “normal.” Since hospital discharge, the child’s weight gain has been slow and she has not achieved appropriate developmental milestones. The next step in the evaluation of this child should be:
A. Thyroid function studies
B. Urine and serum for organic acids
C. Muscle biopsy
D. Brain magnetic resonance imaging (MRI)
E. FISH (fluoresecent in situ hybridation)

E. The child has many signs and symptoms of Rubinstein- Taybi syndrome (16pI3-), a microdeletion syndrome. Routine chromo­some analysis may not identify this syndrome; FISH (fluorescent in situ hybridization) chromosome preparations are revealing.

A very overweight 3-year-old child presents to your office. The mother reports the child to be a product of a normal pregnancy, although she notes the baby did not “move” as much as her other two children. After birth the child was floppy and ate very poorly requiring tube feeds. During the first year of life, however, the child developed a voracious appetite and began to become very obese yet did not grow very tall. The child has been slow in gain¬ing his milestones and appears to be developmentally delayed. The likely etiology for this child’s condition is:
A. Prader- Willi syndrome (paternal 15q 11-13)
B. Angelman syndrome (maternal 15q 11-13)
C. Williams syndrome (7q23-)
D. Wolf-Hirschhorn syndrome (4p-)
E. DiGeorge syndrome (22q 11-)

A. Prader-Willi syndrome (15qll-15) is associated with devel­opmental delay and defective satiety center, such that affected pa­tients will eat constantly.

You see a 14-year-old male in the juvenile detention center where he is currently living after he set a fire in an abandoned building. The boy is tall, slim, underweight, and appears to have especially long legs. His testes are very small for his age and his phallus seems somewhat undersized. His mother reports that he had difficulty with reading, spelling, and mathematics early on, but now seems to be having difficulty in all of his classes. The diagnostic test most likely to identify his problem is:
A. Serum testosterone levels
B. Ultrasonogram of the abdomen
C. Thyroid function studies
D. Referral to pediatric endocrinology
E. Chromosomal analysis

E. Boys with Klinefelter syndrome are tall for their age; the testes are smaller than normal and feel firm and fibrotic. Phys­ical examination often reveals a eunuchoid body habitus and re­duced upper-to-lower body segment ratio secondary to a long lower segment in addition to behavioral and educational problems described in the question. Diagnosis is established by karyotyping.

A very friendly 3-year-old child was referred to you by a local pediatric cardiologist. He is followed by the cardiologist for supravalvular aortic stenosis and by an ophthalmologist for stra-bismus. In addition to the heart murmur and eye findings, your ex-amination reveals a well-appearing child with mild mental retar¬dation, a very round face with full cheeks and lips, an anteverted nose, and a long philtrum. You immediately recognize him to have:
A. Prader- Willi syndrome (paternal 15q 11-13)
B. Angelman syndrome (maternal I 5q 11-13 )
C. Williams syndrome (7q23-)
D. Velocardiofacial syndrome (22ql1.21-ql1.23) ,
E. Alagille syndrome (20pI2-)

C. Williams’ syndrome (7q23-) is associated with aortic stenosis, blue eyes, and cranial facial abnormalities.

the parents of an 8-year-old Down syndrome boy arrive for his an-nual well-child check up. He wants to participate in sports, includ¬ing the Special Olympics. Until further evaluation can be com¬pleted which of the following Sports would you suggest as being safe?
A. Diving
B. Football
C. Tennis
D. Tumbling
E. Wrestling

C. Until lateral cervical flexion-extension films confirm normal anatomy, contact sports, and other activities that may result in forceful flexion of the neck should be avoided.

A small-for-gestation age infant is born to a 35-year-old woman. The infant is noted at birth to have low-set and malformed ears, microcephaly, rocker-bottom feet, inguinal hernias, cleft lip and palate, and micrognathia. Chromosomal analysis is likely to re¬veal which of the following?
A. Holt-Oram syndrome
B. Turner syndrome
C. Edwards syndrome (trisomy 18)
D. Patau syndrome (trisomy 13)
E. Down syndrome (trisomy 21)

C. The description is very characteristic of trisomy 18. Other fea­tures include clenched hands with overlapping digits, small palpebral fissures, prominent occiput, short sternum, and cardiac defects (including ventricular septal defect, atrial septal defect, patent ductus arteriosus, or coarctation of the aorta).

A 4-month-old boy presents for a well-child visit. On physical ex-amination he has a white forelock, a broad mandible, and lateral displacement of the inner canthi. His mother also has a white fore¬lock. Which of the following statements about this child is true?
A. This child is at risk for conductive hearing loss (CHL) and requires an audiologic evaluation.
B. This child is not at risk for hearing loss if his mother has normal hearing.
C. This child is at risk for sensorineural hearing loss (SNHL) and requires an audiologic evaluation.
D. The inheritance pattern of this disorder is X-linked recessive.
E. This child should have ongoing office hearing screening with referral for formal hearing if abnormalities are detected.

C. This child has features of Waardenburg syndrome which in­cludes partial- albinism, often a white forelock, deafness (SNHL), and lateral displacement of the inner canthi, medial flare of the eyebrows, and a broad nasal bridge and mandible. The in­heritance pattern of Waardenburg syndrome is autosomal dom­inant. Children with features of syndromes that are strongly as­sociated with hearing loss require full hearing evaluation.

A mother brings her 3-year-old son who has Down syndrome to the clinic because his gums have been bleeding for a week. Fur¬ther history reveals that he has been less energetic than usual. Examination reveals that the child has a temperature of 100°F (37.8°C) orally, pallor, splenomegaly, gingival bleeding, and bruises on the lower extremities. Which of the following is the most likely explanation for this child’s symptoms?
A. Idiopathic thrombocytopenia
B. Aplastic anemia
C. Leukemia
D. Leukemoid reaction
E. Megaloblastic anemia

C. A high susceptibility to leukemia is associated with certain heritable diseases (including Klinefelter syndrome, Bloom syn¬drome, Fanconi, ataxia telangiectasia, and neurofibromatosis) and chromosomal disorders such as Down syndrome. Children with Down syndrome have a 10- to 15-fold increased risk for developing leukemia compared with normal children. Siblings of an ALL patient have a two- to fourfold increase in chance of developing ALL. A few cases are associated with aberrations in the p53 gene. Overall, these genetic links account for a small number of total ALL cases.

A 7-year-old male with mental retardation was born at home at 26 weeks’ gestation to a 28-year-old mother who had received no prenatal care. A thorough evaluation of this child is likely to sug¬gest his mental retardation related to:
A. Brain tumor
B. Elevated serum lead levels
C. Complications of prematurity
D. Congenital infection with cytomegalovirus
E. Chromosomal aberration

C. Prematurity at birth, especially when < 28 weeks’ gestation, is associated with a variety of complications (such as severe intraventricular hemorrhage) that can result in developmental delay and low IQ.

Match the following genetic disorders (A to E) to the clinical descrip-tion (5-7):
A. Klinefelter syndrome (XXY)
B. XYY male
C. Turner syndrome (XO)
D. Fragile X syndrome
E. XXX syndrome

5- An institutionalized male juvenile delinquent appears at first glance to be normal. Upon closer examination he is noted to have severe nodulocystic acne, mild pectus excavatum, large teeth, prominent glabella, and relatively long face and fingers. His fam¬ily reports that he has poor fine motor skills (such as handwriting), an explosive temper, and a low normal IQ.

6- A tall, thin 14-year-old boy has yet to have any signs of puberty. His mother reports that he was delayed in his speech develop¬ment and always has done less well in school than his siblings. She reports that he is very shy, and teachers report his activity to be immature. Physical examination reveals signs of breast devel¬opment, and long limbs with a decreased upper to lower segment ratio. His testes and phallus are small, and he has no evidence of pubertal development.

7- A 15-year-old with primary amenorrhea is noted to be well below the 5th percentile for height for her age. Her vital signs are sig¬nificant for hypertension. On examination, she has a low poste¬rior hairline, prominent and low-set ears, and excessive nuchal skin.

B. XYY-affected males often have explosive tempers. Other find¬ings include long and asymmetrical ears, increased length versus breadth for the hands, feet and cranial vault, and mild pectus excavatum. By age 5 or 6 years, these boys tend to be taller than their peers, and they begin displaying aggressive/defiant behavior (though this has been questioned recently).

A. With Kleinfelter syndrome (XXY), testosterone replacement allows for more normal adolescent male development, although azoospermia is the rule. The incidence of breast cancer in XXY males approaches that of women.

C. Other features of Turner syndrome include widely spaced nip¬ples and broad chest; cubitus valgus (increased carrying angle of arms); edema of the hands and feet in the newborn period; con¬genital heart disease (including coarctation of the aorta or bicus¬pid aortic valve); horseshoe kidney; short fourth metacarpal and metatarsal; hypothyroidism; and decreased hearing. Mental development is usually normal.

A fair-haired, blue-eyed, mentally retarded 4-year-old girl is prone to fits of uncontrollable laughter. She has midface hy¬poplasia, prognathism (protruding jaw), an unusual gait, and a seizure disorder. She likely has:
A. Wolf-Hirschhorn syndrome (4p-)
B. Angelman syndrome (maternal 15qll-13)
C. Williams syndrome (7q23-)
D. Smith-Magenis syndrome (17pll.2)
E. DiGeorge syndrome (22q 11-)

B. Children with Angelman syndrome (l5qll-13) have inappro­priate bursts of laughter, ataxia, hypopigmented irises, and devel­opmental delay.