Chapter 44. Clinical Neurogenetics Flashcards
Question 44-1:
A woman is diagnosed as having an autosomal dominant condition. Which advice is appropriate regarding counseling?
A. Half of the children wiII have the condition
B. Each child has a 50% chance of having the gene
C. Transmission of the gene is from females to males
D. All are true
Answer 44-1: B.
Each child has a 50% chance of having the
gene. Choice A seems to say the same thing,
but is different in that the genetics predict a
probability rather than a certainty.
Transmission of autosomal dominant genes is
from both sexes to both sexes. (p782)
Question 44-2:
A boy is diagnosed as having a mitochondrial disorder. There are three younger siblings. Neither parent appears to be affected. What is the most appropriate counseling for the patient and family?
A. Each of the siblings has a 50% chance of carrying the gene
B. Transmission is only from females to males
C. Children of the patient will not carry the gene
D. The lack of symptoms in the parents indicates that this is a new mutation in the child, and siblings are not at risk
Answer 44-2: C.
Mitochondrial genes are transmitted from
mother to children of both sexes. As such,
children of affected males will not inherit the
gene. The transmission rate is variable and not
50%. as would be expected from autosomal
dominant inheritance. The lack of symptoms
in mother is not uncommon, since
mitochondrial disorders typically have
extremely variable expression. (P782)
Question 44-3:
A male child is diagnosed as having an X-linked disorder. What would be appropriate counseling for the patient and family?
A. All daughters of the patient will carry the gene
B. None of the sons of the patient will have the gene
C. Females can be affected
D. All are true
Answer 44-3: D.
All of these statements are true. X-linked
transmission is due to a defective gene on the
X-chromosome which in male children is
always from the mother. In female children,
one X-chromosome is obtained from the
father and one from the mother, so all females
are carriers. Females can be affected and are
mosaics. If the disorder is X-linked recessive,
then only males will be affected, whereas if
the disorder is X-linked dominant, then both
sexes will be symptomatic but there will be a
worse clinical presentation in males. (p782)
Question 44-4:
What neurologic disorder is associated with defect of the Y -chromosome?
A. Progressive ataxia
B. Peripheral neuropathy
C. Developmental delay progressing to mental retardation
D. Muscular dystrophy
E. None of these
Answer 44-4: E.
All of the listed conditions can be produced by
genetic defect, however, there are no known
neurologic conditions related to defect of the
Y -chromosome. (P784)
Question 44-5:
Which of the following statements are true regarding trinucleotide repeats in patients with neurologic disease?
A. There can be earlier onset with increases in the repeat number
B. Huntington’s disease is due to unstable triplet repeats
C. Some hereditary spinal cerebellar ataxias are due to unstable triplet repeats
D. Polymerase chain reaction is used to determine the repeat size
E. All of these are true
Answer 44-5; E.
All of these statements are true. Increase in
the number of repeats with successive
generations results in earlier onset of
conditions caused by trinucleotide repeats,
such as myotonic dystrophy. In addition to
myotonic dystrophy, Huntington’s disease,
some hereditary SCAs, Kennedy’s X-linked
spinal-bulbar muscular atrophy, and fragile-X
syndrome have the same genetic features.
(p792-793)
Question 44-6:
Which of the following are autosomal recessive disorders?
1. Tay-Sachs disease
2. Friedreich ‘s ataxia
3. Phenylketonuria.
4. Wilson’s disease
Selectl : A = 1,2, 3. B = 1, 3. C = 2, 4. D= 4 only. E =All
Answer 44-6: E.
All of these are inherited as autosomal
recessive disorders. Patients are symptomatic
if they have inherited the abnormal gene from
both parents who are carriers. Affected
families include children of carrier parents.
Males and females are affected. Multiple
generations can be affected if there is
inbreeding with consanguineous marriages.
(p783)
Question 44-7:
A 40-year-old woman has a parent with Huntington’s disease and has no clinical symptoms. She wants testing for herself. She is status post hysterectomy for ovarian cancer, presumably cured years before. She has no children. Which of the following pieces of information are accurate and appropriate for counseling?
1. Early diagnosis carries no opportunity for early intervention in the disease
2. Testing cannot determine the age of onset of anticipated severity of the disease
3. There is estimated 90010 penetrance by age 60 years
4. Patients homozygous for the gene have a much worse clinical presentation than heterozygous patients
Select: A = 1.2,3. B = 1, 3. C= 2, 4. D= 4 only. E=AII
Answer 44-7: A.
Relatives of patients with Huntington’S
disease frequently want to be tested to
determine whether they carry the gene. The
interest in identification of status not only has
implications for the person presenting, but
also for children of the patient. In this patient,
she is beyond the possibility of producing
children so the counseling is relatively simple
- she has a chance of having the gene, and can
be tested, but there is no intervention which
could be performed if she were shown to have
the gene. If she had children who might carry
the gene and transmit the gene to their
children, the decision would be even more
difficult The testing cannot detennine the age
of onset or severity of the disease. Those with
Huntington’s disease have the same severity
whether homozygous or heterozygous. (p782-
783).
Question 44-8:
A patient is diagnosed with a disorder which is typically thought of as inherited in an autosomal dominant fashion. Parents are no longer living, but apparently lived to advanced age without similar clinical symptoms. Which are possible explanations for this?
1. The parents did not live long enough to express the defective gene and become symptomatic.
2. Alternative parentage should be considered.
3. The patient may have a new mutation.
4. The patient has a recessive condition rather than a dominant condition
Select: A = 1.2.3. B = 1, 3. C = 2. 4. D = 4 only. E = All
Answer 44-8: E.
All of these are possibilities. The most likely
depends on the disorder, since some have a
very low rate of new mutations. Alternative
parentage should always be considered when
there is the apparent new mutation producing
an autosomal dominant disorder. Recessive
conditions should also be conceded, for
example, some hereditary motor sensory
neuropathies are dominant whereas others are
recessive. (p784, 802)
Question 44-9:
A rare inheritance pattern is uniparental disomy. What are the implications of this?
A. A single parent donates two adjacent chromosomes which make up a novel chromosome pair
B. Patients have a single chromosome which would be recessive but is dominant because the single chromosome is unopposed
C. Two of the same chromosomes are inherited from a single parent
D. Genetic material for the chromosome is inherited through the mitochondria, rather than nuclei
Answer 44-9: C.
Uniparental disomy is when both of a certain
chromosome are inherited from a single
parent. A patient may be homozygous for a
defective chromosome because of inheritance
when a single parent was a heterozygote.
(p788)
Question 44-10: Which is the mode of inheritance of familial Alzheimer's disease? A. Autosomal dominant B. Autosomal recessive C. X-linked dominant D. Mitochondrial
Answer 44-10: A.
Familial Alzheimer’s disease is inherited as
autosomal dominant, and early onset is linked
with chromosomes 14 and 21, whereas late
onset is linked to chromosome 19. (p805-806)
