CME

Multiple-Choice Questions

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issue after April 30, 2014.

TYPE A QUESTIONS (SINGLE BEST ANSWER)

b 1. A 50-year-old man is evaluated for progressive personality and behavioral
changes over the past 10 months. He has become socially withdrawn,
showing disinterest for his family and lack of empathy for others, and has
developed perseverative and socially inappropriate behaviors. Over the past
4 months, he has developed difficulty swallowing, dysarthria, and weakness
of the limbs. On examination, he has no insight into his condition. He has
reduced attention span and tendency to verbal and motor perseveration.
Visuospatial, language, and memory functions are relatively preserved. He has
a flaccid dysarthria; tongue atrophy and fasciculations; and mild weakness,
atrophy, and fasciculations in proximal upper and lower extremity muscles.
This disorder has been associated with a mutation affecting which of the
following proteins?
A. dynactin 1
B. presenilin 1
C. senataxin
D. ubiquitin
E. valosin-containing protein

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 Multiple-Choice Questions

b 2. A 33-year-old man is evaluated for progressive weakness in the arms and

legs and shortness of breath with exertion. Examination shows weakness and
atrophy in the forearm flexors and extensors, tibialis, and gastrocnemius
muscles. EMG shows myopathic changes and increased insertional activity.
Nerve conduction velocities are reduced in the lower limbs. Echocardiogram
shows a cardiomyopathy. Muscle biopsy shows the presence of amorphous,
granular, or hyaline congophilic deposits. Electron microscopy shows
disintegration of myofibrils at the Z disk. This disorder can be associated with
a mutation affecting which of the following genes?
A. caveolin
B. dysferlin
C. emerin
D. lamin A/C
E. myotilin

b 3. A husband and wife present to a genetic counselor for advice concerning

reproductive options. The husband is a 28-year-old man whose father died
of Huntington disease (HD) at the age of 64; the husband has never been
tested for the HD gene mutation. Both wish to be biological parents, but
the husband does not want to know his mutation status. Which of the
following options is most appropriate for this couple?
A. amniocentesis
B. chorionic villus sampling
C. donor gametes for artificial insemination
D. in vitro fertilization with preimplantation genetic diagnosis
E. preconceptual carrier testing

b 4. A 55-year-old Japanese man with a history of allergy to aspirin experiences

a transient episode of left upper extremity paresis. A carotid ultrasound
shows 50% stenosis of the right internal carotid artery. Magnetic resonance
angiogram, transesophageal echocardiogram, Holter monitoring, and studies
for hypercoagulability are all normal. He is started on clopidogrel 75 mg.
While on clopidogrel, he has a right middle cerebral artery distribution
stroke. He is found to have a polymorphism in the cytochrome P450, family
2, subfamily C, polypeptide 19 gene, CYP2C19. What is the consequence
of this polymorphism?
A. decreased binding of clopidogrel to the platelet P2Y12 receptors
B. decreased intestinal absorption of clopidogrel
C. decreased production of an active clopidogrel metabolite
D. increased inactivation of clopidogrel by esterases
E. increased risk of clopidogrel-induced thrombocytopenic thrombotic purpura

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b 5. Which of the following clinical features is more characteristic of myotonic
dystrophy type 2 than myotonic dystrophy type 1?
A. absent muscle pain
B. anticipation
C. cataracts
D. congenital form of the disease
E. proximal weakness

b 6. A 33-year-old man is evaluated for peripheral neuropathy. He is found to

have hepatosplenomegaly. Complete blood count shows anemia and
thrombocytopenia. A bone marrow biopsy shows glycosphingolipid-laden
macrophages. He has undetectable !-glucocerebrosidase in white blood cells.
This patient is at increased risk to develop which of the following conditions?
A. frontotemporal dementia
B. multiple strokes
C. Parkinson disease
D. progressive external ophthalmoplegia
E. spinocerebellar ataxia

b 7. A 24-year old asymptomatic woman requests counseling regarding genetic

testing for the survival of motor neuron gene, SMN. She has a 14-year-old
brother with spinal muscular atrophy and wants to know whether she is a
carrier of the mutation as she wishes to become pregnant. Which of the
following is the most appropriate counseling in her case?
A. carrier detection is recommended to help family planning
B. testing for SMN mutations is only indicated for prenatal diagnosis
C. testing in asymptomatic subjects is discouraged given the lack of
specific treatment
D. testing is not cost-effective given the low prevalence of mutations
E. testing is required to detect risk of cardiomyopathy in the asymptomatic
carrier

b 8. Mutations in the microtubule-associated protein tau gene, MAPT, lead to

frontotemporal dementia due to intraneuronal aggregation of which of
the following proteins?
A. amyloid-"
B. hyperphosphorylated tau
C. prion protein
D. TAR DNAYbinding protein 43 (TDP-43)
E. ubiquitin

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 Multiple-Choice Questions

b 9. A 66-year-old Japanese woman with a history of hypertension and diabetes

is evaluated 5 hours after a left middle cerebral artery territory ischemic
stroke. Her carotid ultrasound shows 60% stenosis of the left internal carotid
artery. An EKG shows atrial fibrillation. The echocardiogram shows no clot
and an ejection fraction of 50%. Her physician orders a gene test to detect
vitamin K epoxide reductase complex, subunit 1 gene, VKORC1,
polymorphisms. What is the rationale for ordering this test?
A. to assess the possibility of a protein C or protein S deficiency
B. to assess the risk of heparin-induced thrombocytopenia
C. to determine the potential benefit of factor IIA (thrombin) inhibitors
D. to determine the risk of clopidogrel-induced thrombocytopenic purpura
E. to optimize dosage of warfarin

b 10. A 5-year-old boy is brought to the office by his mother. She is concerned
that the child may have a congenital neuropathy because she was recently
diagnosed with autosomal dominant Charcot-Marie-Tooth disease type 1A
due to a PMP22 duplication. The child, who has no siblings, has had normal
developmental milestones, has no motor or sensory symptoms, and has a
normal neurologic examination. Which of the following is the most
appropriate approach to testing of the child?
A. chromosomal microarray testing
B. needle EMG
C. nerve conduction studies
D. no testing is appropriate
E. PMP22 gene testing

b 11. A 33-year-old man with a family history of Parkinson disease (PD) is aware
that low vitamin D has been associated with increased risk of developing
multiple sclerosis. He wonders whether he should take vitamin D to reduce
the risk of developing PD. Which of the following statements regarding the
relationship between vitamin D and PD is supported by current evidence?
A. A single nucleotide polymorphism of the vitamin D receptor that
increases risk of multiple sclerosis decreases risk for PD.
B. High vitamin D levels may lower the relative risk for PD.
C. Unlike patients with multiple sclerosis, patients with PD have higher
vitamin D levels than controls.
D. Vitamin D is unlikely to be protective, as its plasma levels increase with age.
E. Vitamin D has not yet been shown to be neuroprotective in
experimental models of PD.

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b 12. A 65-year-old woman is evaluated for progressive difficulties with memory
over the past 8 months. Examination shows that she has normal orientation,
attention span, language, and visuospatial abilities but is unable to recall the
name of four objects after 5 minutes. Her MRI shows moderate bilateral mesial
temporal atrophy. Deoxyglucose scan shows reduced temporoparietal
metabolism in the precuneus and posterior cingulate gyrus. Which of the
following molecules has been recently identified as a potential risk factor for
this patient’s condition?
A. dynactin 1
B. progranulin
C. sortilin-related receptor
D. TAR DNAYbinding protein 43 (TDP-43)
E. valosin-containing protein

b 13. A 55-year-old woman with hypercholesterolemia is started on simvastatin.

One week after starting treatment she develops myalgia, weakness of the
quadriceps muscles, and elevation of serum creatine kinase to 100 times
normal. Polymorphism of which of the following genes could have
predisposed her to this complication?
A. CYP2C9
B. GBA
C. ITGB3
D. SLCO1B1
E. VKORC1

b 14. A 28-year-old woman presents to the office with a 2-year history of muscle
soreness and cramps and mild weakness. She is the mother of two boys
with Duchenne muscular dystrophy. Examination shows mild hip flexor
weakness. Serum creatine kinase is mildly elevated; other routine laboratory
tests, including thyroid function tests, are normal. Which of the following is
the most likely genetic explanation for her presentation?
A. autosomal dominant inheritance
B. autosomal recessive inheritance
C. mitochondrial inheritance
D. nonrandom X-chromosome inactivation
E. X-linked dominant inheritance

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 Multiple-Choice Questions

b 15. A 16-year-old girl is evaluated for progressive difficulty walking over the past
4 years. She first noticed that she would often trip when walking on uneven
ground. Over the past 3 months she has developed bilateral footdrop. She has
also noticed numbness in both feet. Her father, who died at age 60 of a
myocardial infarction, had a neuropathy, but she cannot provide more details.
Examination shows a steppage gait, atrophy of leg muscles, pes cavus, and
hammer toes. There is weakness and atrophy of hand muscles and severe
weakness of all muscles innervated by the tibial and peroneal nerves. Reflexes
are absent at the ankles. There is moderate sensory loss to all modalities in
the feet. EMG shows reduced compound muscle action potential amplitudes
with only mild decrease in nerve conduction velocities; there are fibrillation
potentials and large motor unit potentials in the anterior tibialis, posterior
tibialis, peroneus longus, and medial gastrocnemius muscles. Genetic testing
is most likely to reveal a mutation in which of the following genes?
A. HSPB8
B. MFN2
C. NEFL
D. PMP22
E. RAB7

b 16. A 40-year-old asymptomatic woman requests genetic testing for Alzheimer

disease. Her father developed the disease at age 55 and died 6 years later.
Her 52-year-old brother has amnestic mild cognitive impairment. She is
concerned about being a carrier of a mutation and transmitting the disease to
her 12-year-old son. Her neurologic examination, including mental status
testing, is normal. What is the most appropriate next approach for the
physician?
A. contact the brother’s physician and suggest he be tested for presenilin
type 1 mutations
B. refer the patient for pretest genetic counseling and psychological assessment
C. test for APOE (4 allele and, if present, refer for genetic counseling
D. test for presenilin type 1 mutation and, if present, refer for genetic counseling
E. test the patient and her son for both presenilin type 1 and presenilin
type 2 mutations

b 17. A 26-year-old Taiwanese-American man comes to the office for follow-up

of a 1-year history of partial complex seizures with secondary generalization
that have recurred despite treatment with levetiracetam. Treatment with
carbamazepine is being considered. Testing for which of the following genes
should be performed prior to initiating treatment with carbamazepine in
this patient?
A. ABCG2
B. CYP2C9
C. HLA-B*1502
D. P2RY12
E. VKORC1

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b 18. A 44-year-old Brazilian man is evaluated for progressive gait ataxia and
dysarthria over the past 14 months. The patient’s father, who is Portuguese
Azorean, was diagnosed with motor neuron disease when he was 70 years
old. Neurologic examination reveals dysarthria, ataxic gait, and limb
dysmetria. Mild rigidity is present in the upper and lower limbs. Reflexes are
absent at the ankles. Which of the following types of spinocerebellar ataxia
(SCA) is most likely to be diagnosed on the basis of the ataxia testing panel?
A. SCA1
B. SCA2
C. SCA3
D. SCA6
E. SCA7

b 19. An 18-year-old woman is evaluated for progressive difficulty walking over

the past 2 years. Both her father and brother have been diagnosed with
peripheral neuropathy. Examination shows a steppage gait, atrophy of leg
muscles, pes cavus, and hammer toes. Mild weakness and atrophy of hand
muscles and moderately severe weakness of all leg muscles are present. She
has areflexia at the ankles and knees. There is loss of vibration sense at the
toes. EMG shows reduced compound muscle and sensory action potential
amplitudes with mild decrease in nerve conduction velocities; there are
fibrillation potentials and large motor unit potentials in the thenar and leg
muscles. Genetic testing shows a mutation in the mitofusin 2 gene, MFN2.
Which additional manifestation may be found in members of this family?
A. anhidrosis
B. hearing loss
C. optic atrophy
D. scoliosis
E. spasticity

b 20. A 50-year-old man is evaluated for a 10-month history of cognitive and

speech difficulties. He has difficulty naming and even recognizing persons
or objects that used to be familiar to him. His father died at age 65, 5 years after
developing an illness characterized by personality and behavioral changes.
He has a 55-year-old sister who developed progressive difficulty articulating
words. On examination, he speaks fluently and has normal attention, executive
function, and visual spatial memory. He names only 15 of 30 objects in the
Boston Naming test and generates a list of only three animals in 1 minute. The
brain of his father is available for neuropathologic analysis and shows neuronal
loss and gliosis in the frontoparietal regions associated with inclusions
immunoreactive for TAR DNAYbinding protein 43. Mutations in which of the
following genes are most likely to be found in this family?
A. DCTN1
B. GRN
C. MAPT
D. PRNP
E. SORL1

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 Multiple-Choice Questions

b 21. The Genetic Information Nondiscrimination Act provides protection

from employment and health insurance discrimination based on genetic
information involving which of the following groups?
A. military personnel
B. persons applying for disability insurance
C. persons applying for life insurance
D. persons who are asymptomatic
E. persons with a diagnosis of genetic disease

b 22. An 8-year-old boy is evaluated for progressive difficulty walking, climbing

stairs, and running over the past 2 years. He has no family history of
muscle disease. Examination shows moderate proximal lower extremity
weakness and enlarged calves. His creatine kinase is 100 times elevated.
A complete screening fails to show deletions and duplications of the
dystrophin gene. Which of the following is the most appropriate next step
for diagnosis of his condition?
A. dystrophin gene sequencing
B. EMG to exclude spinal muscular atrophy
C. muscle biopsy with immunostaining for dysferlin
D. Southern blotting to detect partial D4Z4 repeat deletions
E. testing for lamin A/C mutations

b 23. A 34-year-old woman with a history of migraines is evaluated for

acute-onset dysarthria and hand weakness. A head MRI shows an acute
lacunar infarction in the right internal capsule. Evidence of leukoaraiosis and
two subcortical microhemorrhages in the left hemisphere also exists. Her
father had an MRI for evaluation of headaches and was found to have
extensive leukoaraiosis. Her uncle had depression and early-onset dementia.
A mutation of which of the following genes is most likely in this family?
A. ATPA2
B. CBS
C. GLA
D. MRM1
E. NOTCH3

b 24. Which of the following genetic diseases is associated with decreased

number, rather than expansion, of a small repeat element?
A. facioscapulohumeral muscular dystrophy
B. fragile X syndrome
C. Huntington disease
D. myotonic dystrophy type 1
E. myotonic dystrophy type 2

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b 25. A 22-year-old student is evaluated for progressive difficulties in sports
performance over the past 6 years. He often trips and falls when he runs. He
is accompanied by his 40-year old father, who has recently experienced
gait imbalance, and his 18-year old sister, who has always been a slow runner
because of weak ankles. Examination shows pes cavus; difficulties walking
on heels and toes; atrophy of the anterolateral and posterior compartment
muscles; weakness of anterior tibialis, peronei, posterior tibialis, toe flexors, and
extensors; and absent ankle jerks. Sensation to vibration and joint position
are reduced in the feet. The EMG shows slow nerve conduction velocities
(20 m/s in all nerves tested). Needle examination is normal. Examinations of
his father and sister show that both have pes cavus and absent ankle jerks. Which
of the following is the most likely genetic alteration to be found in this family?
A. GJB1 point mutation
B. MFN2 deletion
C. MBP duplication
D. MPZ point mutation
E. PMP22 duplication

b 26. The recent practice guidelines for the genetic testing and counseling
of Alzheimer disease (AD) from the American College of Medical Genetics
and the National Society of Genetic Counselors suggest that APOE testing for
AD risk in an asymptomatic individual could be appropriately considered
in which of the following situations?
A. after genetic counseling using a strict pretesting and posttesting counseling
protocol
B. in patients who have negative testing for autosomal dominant early-onset
forms of AD
C. in patients with a family history of AD applying for long-term disability insurance
D. there is no clinical situation where APOE testing is appropriate
E. upon request by any patient as part of routine susceptibility assessment

b 27. A 24-year-old man is evaluated for progressive hand and leg weakness. He
first started noticing inability to hold a pen when he was 10 years old. When
he was 15 years old he developed progressive foot weakness and eventually
bilateral footdrop requiring ankle-foot orthoses. Both his mother and maternal
grandmother had a history of mild foot weakness. Examination shows a
steppage gait; pes cavus; and severe weakness and atrophy of thenar,
hypothenar, peroneal, and tibialis muscles. Reflexes are absent throughout.
There is sensory loss in the hands and feet. Nerve conduction study shows
reduced amplitude of compound motor and sensory action potentials. Median,
ulnar, peroneal, and tibial nerve conduction velocities are in the intermediate
range (30 m/s to 35 m/s). This disorder is most likely linked to a mutation
affecting which of the following proteins?
A. connexin 32
B. dynactin 1
C. mitofusin 2
D. myelin basic protein
E. peripheral myelin protein 22

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 Multiple-Choice Questions

b 28. Of the following list of genes and the disease states associated with them,
which of the genes is a polymorphism rather than a mutation?
A. APOE gene and Alzheimer disease
B. GLA gene and Fabry disease
C. HTT gene and Huntington disease
D. PMP22 gene and Charcot-Marie-Tooth disease
E. SPAST gene and hereditary spastic paraplegia

b 29. A 44-year-old man is evaluated for bilateral hand tremor. Examination

shows postural hand tremor and mild head tremor. There is no evidence of
parkinsonism. The tremor improves with propranolol. His father has head
and hand tremor. This condition has shown association with a variant of the
gene encoding which of the following proteins?
A. ATPase !2 subunit
B. dynactin 1
C. LINGO1
D. PINK1
E. tyrosine hydrolyase

b 30. A 26-year-old man is evaluated for a 4-year history of mild progressive

difficulty with gait, weakness in his feet and hands, and tingling in his toes.
Examination shows bilateral pes cavus, mild weakness of intrinsic hand muscles
and foot dorsiflexors, moderate vibratory sense loss in the toes, diminished
distal reflexes, and inability to walk on his heels. Nerve conduction velocities are
mildly symmetrically slow in motor and sensory nerves of the upper and lower
extremities. Laboratory testing confirms a GJB1 mutation consistent with
Charcot-Marie-Tooth disease type 1X. What is the approximate likelihood that
this patient will pass this gene on to one of his sons?
A. 0%
B. 25%
C. 50%
D. 75%
E. 100%

b 31. A 65-year-old man of Arab-Berber ancestry developed mild right upper

extremity tremor 6 months ago. His grandmother developed Parkinson disease at
age 70. Genetic testing shows that he has a G2019S variant of the leucine-rich repeat
kinase 2 gene, LRRK2. Which of the following is an implication of this finding?
A. he is at risk of developing rapidly progressive, levodopa-resistant parkinsonism
B. he should be tested for the G2385 variant, which is prevalent in this
ethnic group
C. his asymptomatic 12-year-old grandson should be tested because this is
an autosomal dominant familial form of Parkinson disease
D. this variant is present in up to 40% of Parkinson disease cases in this
ethnic group
E. this variant is probably not associated with familial Parkinson disease in
his case

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b 32. A 4-year-old boy with a diagnosis of autism spectrum disorder is brought
to the office by his parents for further etiologic evaluation. There is no family
history of neurologic disease. Examination shows no stigmata of a specific
cause for his syndrome, such as tuberous sclerosis or fragile X syndrome, and
recent MRI imaging is normal. Which of the following genetic tests is the
most appropriate for this patient?
A. chromosomal microarray
B. individual gene testing for the most common genetic causes of autism
C. interphase fluorescent in situ hybridization (FISH) analysis
D. metaphase FISH analysis
E. standard karyotype analysis

b 33. A 72-year-old man is evaluated for mild difficulties with memory, particularly
for names, over the past 6 months. The patient’s wife has also noticed the
memory problems, but they have not interfered with his job, family, or social
activities. He has an asymptomatic 50-year-old son. Mental status examination is
consistent with mild cognitive impairment, amnestic type. Which of the following
is the most appropriate statement regarding APOE genotyping in this patient?
A. APOE testing is not useful because he only has mild cognitive impairment.
B. If he has an APOE (4/(4 genotype, his asymptomatic son should also
be tested.
C. If he lacks the APOE (4 status, he has a 3% per year risk of developing
Alzheimer disease.
D. The (2 genotype virtually excludes Alzheimer pathology as the cause of
his symptoms.
E. The (4 genotype increases the risk of progression to Alzheimer disease.

b 34. A 66-year-old woman is evaluated for a left middle cerebral artery

distribution stroke 12 hours ago. She is found to have atrial fibrillation.
Polymorphisms of which of the following genes may affect the requirements
of warfarin in this patient?
A. ABCG2
B. CYP2C19
C. P2Y12R
D. SLCO1B1
E. VKORC1

b 35. A 58-year-old man with a 4-year history of progressive dementia is diagnosed

with Alzheimer disease (AD). His father died of dementia at the age of 60, and
one of his brothers died of autopsy-confirmed AD at age 62. This patient is most
likely to have a mutation in a gene encoding which of the following proteins?
A. amyloid precursor protein
B. ApoE
C. presenilin 1
D. presenilin 2
E. progranulin

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 Multiple-Choice Questions

b 36. A 42-year-old man is evaluated for progressive leg weakness with bilateral
footdrop, loss of manual dexterity, and stiffness in his hands. Examination
shows male pattern baldness, ptosis, weakness of the lower face, and atrophy
of the temporalis and masseter muscles. Percussion myotonia is elicited in
the thenar muscles. Which of the following is the primary mechanism of the
patient’s findings?
A. disruption of intracellular calcium homeostasis
B. disruption of the submembrane cytoskeleton
C. impaired function of the dystrophia myotonica-protein kinase gene, DMPK,
leading to abnormal channel phosphorylation
D. impaired maintenance of the myofibrillary apparatus
E. toxic effects of expanded messenger RNA (mRNA) leading to abnormal
mRNA splicing

b 37. A 45-year-old man is evaluated for progressive gait instability, orthostatic

dizziness, and urinary incontinence for the past 6 months. Examination
shows cerebellar ataxia, dysarthria, and mild rigidity in the upper and lower
extremities. He has orthostatic hypotension. Postvoid residual volume is 300
mL. An MRI shows atrophy of middle cerebellar peduncles and pons with the
hot cross bun sign. Which of the following genetic loci has been associated
with risk of developing this condition?
A. ATN1
B. ATXN3
C. CACNA1A
D. GLA
E. SNCA

b 38. A 17-year-old man is evaluated for weakness in the shoulder and arm
muscles and prominent contractures in the elbows, ankles, and neck. He toe
walked as a child and first noticed stiff elbows and ankles 6 years ago. His
brother died suddenly at age 20. Examination shows contracture in the neck
extensor muscles, elbows, and ankles, and mild symmetric weakness and
atrophy in the biceps and triceps. His creatine kinase is elevated (10 times
normal). Muscle biopsy shows increased endomysial tissue and fatty
replacement. EKG shows atrial fibrillation and a second-degree atrioventricular
block. Which of the following is the most likely cause of this disorder?
A. autosomal dominant D4Z4 repeat deletion
B. autosomal dominant mutation of the caveolin gene
C. autosomal recessive mutations of the calpain gene
D. CTG expansion of the dystrophia myotonica-protein kinase gene, DMPK
E. X-linked mutation of the emerin gene

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b 39. A 60-year-old man is evaluated for slowly progressive ataxia, bilateral hand
tremor, and urinary urgency over the past 3 years. He comes to the
consultation with his 25-year-old daughter, who is pregnant with an 18-week
male fetus, and his 35-year-old son, who has an 11-year-old daughter.
Examination reveals an ataxic gait, mild bilateral tremor at rest, and
hyporeflexia in the lower limbs. An MRI of the head shows increased
T2 signal in the middle cerebellar peduncles. Genetic testing shows that
he has 120 CGG repeats in the fragile X mental retardation 1 gene, FMR1.
Which of the following concerns should be discussed during genetic
counseling with this family?
A. the patient’s daughter is at 50% risk to have inherited her father’s
premutation
B. the patient’s 11-year-old granddaughter is at risk of developing ovarian
failure
C. the patient’s son is an obligate carrier of the mutation
D. the patient’s son is at risk of developing dementia at a later age
E. the patient’s unborn grandson is at risk of mental retardation

b 40. A 23-year-old man is evaluated for numbness and burning sensation in

the feet, numbness in the hands, episodes of lancinating pain in the lower
limbs, and progressive gait difficulties over the past 3 years. On one occasion
he hurt his right foot while playing soccer but only became aware of this
after he saw swelling around the ankle. He has a history of problems with
calluses and pressure sores from shoes and has more recently developed foot
ulcerations. His father and brother have the same symptoms. Examination
shows loss of pinprick and temperature sensation in the hands and feet and
loss of joint position and vibration sense in the toes. This disorder has
been associated with a mutation of which of the following genes?
A. GALA
B. GJB1
C. SCN9A
D. SPTLC1
E. TRKA

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