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The answer is c. This child has Prader-Willi Syndrome (PWS). Infants with PWS are often hypotonic and may have difficulty gaining weight because of slow feeding. Their neurocognitive development is slow and most children ultimately do not achieve normal intelligence. Obesity caused by uncontrolled hunger is frequent. These children are often growth hormone deficient and have hypogonadism. The FISH test of the 15q11.2-q13 region detects most children with PWS. However, a specific methylation DNA test does exist that detects those children who inherit the condition as a result of parental disomy, and should be obtained in those children who fit the clinical phenotype for PWS but have normal FISH evaluations. Routine chromosomal testing will be normal in PWS, and although it is not “wrong” to order this test as part of the evaluation of a syndromic developmentally delayed child, it is not the best answer. Deletions
and rearrangements in the subtelomeric regions of the chromosomes are associated with syndromic mental retardation but again, is not a test that detects PWS. Mutations in the MECP2 gene are the cause of Rett syndrome. Elevated lactic acid levels are indicative of many different disorders and are not helpful or specific in detecting PWS.

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The answer is b. This child has NF1, which is an autosomal-dominant disorder. The incidence of NF1 is approximately 1 in 4000 individuals, and this incidence does not vary across ethnic groups. Mutations in the NF1 gene located on the 17th chromosome are responsible for the disease, but there is no one specific mutation that causes the disease; dozens of mutations have been described. Approximately one half of affected individuals inherit the gene from an affected parent, whereas the other half develops the mutation as a result of a spontaneous mutation. Regardless, if one parent has the mutation, the risk with each pregnancy is half, as this is an autosomal-dominant disorder.

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The answer is a. This girl is affected with the X-linked disorder ornithine transcarbamylase deficiency. This enzyme is one of the urea acid cycle enzymes. In boys, the defect is lethal at an early age, but because girls have two X chromosomes, the relative deficiency of this enzyme can present as intermittent hyperammonemia, with vomiting as a key feature, especially during viral illnesses. It is important to remember that “BUN” means simply “urea level” and the BUN will be low in all urea acid cycle defects and in the organic acidurias, which inhibit the urea acid cycle. (If you see a dehydrated and ill-appearing child with a BUN of 0, 1, 2, or 3, think of ordering an ammonia level test.) Elevated glycine levels can occur in nonketotic hyperglycinemia, which usually presents as a catastrophic seizure disorder in infancy. Low CSF glucose in the context of an acellular CSF occurring in an infant with seizures is a clue for glucose transport disorder.

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The answer is d. Olfactory hallucinations are most often caused by seizures originating in the lower portion of the frontal lobes. Children will describe the event as a horrible smell, like a skunk or burnt rubber. Such a symptom should indicate to the physician a structural abnormality in the brain and warrants MRI testing. The other symptoms are among the most common features of pediatric migraine, which is reported to occur in approximately 5% of all children.

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The answer is d. This boy is affected with both narcolepsy (the sudden onset of sleep at inappropriate times) and cataplexy (sudden onset of sleep initiated by laughter, fear, or surprise). Simple narcolepsy occurs in approximately 1:1000 individuals, although cataplexy is a rare form of the illness. Individuals with narcolepsy often have other sleep disorders, such as hypnagogic hallucinations—vivid, realistic, and often frightening dreams; and sleep paralysis—temporary inability to move, which occurs upon awakening from sleep. The polysomnogram (sleep study) offers an analysis of the efficiency of sleep, to make sure the child does not have sleep apnea or other sleep disorders. The MSLT provides a systematic analysis of how quickly the child falls asleep after a “good night’s sleep.” Treatment with psychostimulants is often effective. Sleep disorders in children are underdiagnosed and can only be evaluated and treated if they are considered in the differential diagnosis.

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The answer is d. Myotonic dystrophy is an autosomaldominant disorder that is caused by a trinucleotide repeat, meaning that the condition can worsen with successive generations. Individuals with this condition have very poor muscle bulk and have a thin hatchet-like face. Cognitive delays are common, but not universal, and it is not uncommon for older family members to have escaped diagnosis. The myopathy is also variable, but a common feature is myotonia—an abnormal sustained contraction of muscle groups when the muscle is contracted. This causes difficultly releasing the handgrip when shaking hands or turning a doorknob. Early balding, cataracts, diabetes mellitus, hypothyroidism, and cardiac conduction defects can also be part of this condition. Central core disease is another autosomaldominant muscle disease that causes thin facies and mild weakness, but intelligence is normal. Although attention deficits are often part of myotonic dystrophy, the family history and abnormal neurologic examination should clue the doctor into thinking further than the obvious presenting complaint. Despite the fact that the child is underweight, there is nothing in the history to suggest malnutrition.

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The answer is e. Infants of women with myotonic dystrophy who also are affected by disease (the 50% that inherit the gene defect) can present in the delivery room with severe hypotonia, to the point that intubation and ventilation are required. The only treatment is supportive care and over time the infant will likely gain enough strength to be self-sufficient. Sepsis should be considered in this situation. There are infants with PWS who are profoundly hypotonic at birth, but the mother’s examination in this scenario suggests myotonic dystrophy. There is no suggestion that birth anoxia plays any role in this case. Leigh syndrome, which does not present in the delivery room, is a progressive disorder marked by seemingly normal development followed by stepwise
neurologic decline and respiratory failure resulting from disorders of energy metabolism.

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The answer is b. This clinical picture is most consistent with infantile botulism. Ingestion of the botulinum spore (found in honey or the dirt of certain regions) can result in this illness. Approximately 90% of reported cases in the United States are from California, Utah, and southeast Pennsylvania, likely because of high concentrations of Clostridium botulinum spores in the soil of these regions. This disorder usually presents before the first birthday in a previously healthy child. Subacute weakness and constipation are the key features, with a preserved mental status. Although the child may appear lethargic, she is in fact quite alert but simply too weak to move because the toxin affects the neuromuscular junction. Treatment is supportive, although botulinum immune globulin has been used to shorten the course of the illness. The presentation of the weakness in spinal muscular atrophy is more chronic and the constipation is not a key feature, but this is a good thought and should be kept in mind. Also, the papillary light reflex is normal in spinal muscular atrophy but not in infantile botulism. This case is not the typical clinical presentation of sepsis or nonaccidental trauma. Infants with intussusception may have altered mental status but they are not hypotonic.

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The answer is c. This scenario is most consistent with a postconcussive syndrome. The pathophysiology of this disorder, which tends to follow relatively mild head trauma and concussions, is not understood. Within a few weeks of the injury, and after an apparent recovery, the child develops headaches, difficulty in concentrating, poor memory, and dizziness, along with other somatic complaints that have no clear etiology. The MRI/CT scan and EEG are normal in this syndrome, although these tests are not needed to diagnose or evaluate for postconcussive syndrome. Treatment is supportive care. The use of antidepressant medication is sometimes helpful, as are psychostimulant medications. Although the educational program must be adjusted to meet the ability of the patient, the patient should not be allowed to either stop schooling or be kept at home during the recovery. A complete recovery occurs in weeks to months. Although there may be a psychological component to the illness, it is not a primary psychiatric condition. Delayed subdural hemorrhages are rare in children, but it is often not practical not to evaluate for this possibility given how poorly functional these children may be during the presenting days of the syndrome. Trauma-triggered migraine is a disorder in which the migraine, with a distinct beginning and end, is triggered by a very mild head trauma, such as bumping against a wall. Because of the social history surrounding the accident and the punishment, it is difficult to sort out what could be a conversion disorder in this case. Finally, seizures can occur after head injury, but there is nothing about the history to suggest that the patient is having epileptic events.