Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_4455_Библиотеки_им_академика_М_И_Перельмана
.pdf
412 Disorders of the Auditory System
https://t.me/medicina_free
K. (2004). Temporal course of auditory hallucinations. British Journal of Psychiatry, 185,
516–517.
Shergill, S. S., Murray, R. M., & McGuire, P. K.
(1998). Auditory hallucinations: A review
of psychological treatments. Schizophrenia
Research, 32(3), 137–150.
Sood, S. K., & Coles, R. R. A. (1988). Hyperacu-
sis and phonophobia in tinnitus patients.
British Journal of Audiology, 22, 228.
Sullivan, M., Katon, W., Russo, J., Dobie, R.,
& Sakai, C. (1993). A randomized trial of
nortriptyline for severe chronic tinnitus.
Effects on depression, disability, and tinnitus symptoms. Archives of Internal Medicine,
153(19), 2251–2259.
Sweetow, R. W. (2000). Cognitive-behavior
modification. In R. S. Tyler (Ed.), Tinnitus
handbook (pp. 297–311). San Diego, CA: Singular Publishing.
Tien, A. Y. (1991). Distributions of hallucina-
tions in the population. Social Psychiatry and
Psychiatric Epidemiology, 26(6), 287–292.
Tiihonen, J., Hari, R., Naukkarinen, H., Rimón,
R., Jousmäki, V., & Kajola, M. (1992). Modified activity of the human auditory cortex
during auditory hallucinations. American
Journal of Psychiatry, 149(2), 255–257.
Tonndorf, J. (1980). Acute cochlear disorders:
The combination of hearing loss, recruitment, poor speech discrimination, and tinnitus. Annals of Otology, Rhinology, and Lar-
yngology, 89(4, Pt. 1), 353–358.
Tonndorf, J. (1987). The analogy between tin-
nitus and pain: A suggestion for a physiological basis of chronic tinnitus. Hearing
Research, 28(2–3), 271–275.
Traynor, R. M. (2018). Heard but not seen:
Tinnitus and auditory hallucinations. The
ASHA Leader, 23(12), 20–21.
Tunkel, D. E., Bauer, C. A., Sun, G. H., Rosen-
feld, R. M., Chandrasekhar, S. S., Cunningham, E. R., Jr., . . . Whamond, E. J. (2014).
Clinical practice guideline: Tinnitus. Oto-
laryngology-Head and Neck Surgery, 151(2
Suppl.), S1–S40.
Tyler, R. S., & Erlandsson, S. (2003). Manage-
ment of the tinnitus patient. In L. Luxon,
J. M. Furman, A. Martini, & D. Stephens
(Eds.), Audiological medicine: Clinical aspects
of hearing and balance (pp. 571–578). London,
UK: Martin Dunitz.
Vernon, J. A. (1975). Tinnitus. Hearing Aid Jour-
nal, 13, 82–83.
Vernon, J. A., & Meikle, M. B. (1988). Measure-
ment of tinnitus: An update. In M. Kitahara
(Ed.), Tinnitus: Pathophysiology, diagnosis,
and treatment (pp. 36–52). Tokyo, Japan:
Igaku-Shoin.
Vernon, J. A., & Meikle, M. B. (2000). Tinnitus
masking. In R. S. Tyler (Ed.), Tinnitus hand-
book (pp. 313–356). San Diego, CA: Singular
Publishing.
Wang, H. T., Luo, B., Huang, Y. N., Zhou, K. Q.,
& Chen, L. (2008). Sodium salicylate suppresses serotonin-induced enhancement of
GABAergic spontaneous inhibitory postsynaptic currents in rat inferior colliculus
in vitro. Hearing Research, 236(1–2), 42–51.
Waters, F., Allen, P., Aleman, A., Fernyhough,
C., Woodward, T. S., Badcock, J. C., . . .
Larøi, F. (2012). Auditory hallucinations in
schizophrenia and nonschizophrenia populations: A review and integrated model of
cognitive mechanisms. Schizophrenia Bulle-
tin, 38(4), 683–693.
Wilson, P. H., & Henry, J. (2000). Psychological
management of tinnitus. In R. S. Tyler (Ed.),
Tinnitus handbook (pp. 263–279). San Diego,
CA: Singular Publishing.
Wilson, P. H., Henry, J., Bowen, M., & Hara-
lambous, G. (1991). Tinnitus Reaction
Questionnaire: Psychometric properties of
a measure of distress associated with tinnitus. Journal of Speech and Hearing Research,
34(1), 197–201.
9
https://t.me/medicina_free
Hereditary and Congenital
Hearing Loss
intRoduction
Genetics has emerged as an important
topic in the field of audiology today. It
is particularly valuable for the audiologist and health care professional to have a
fundamental knowledge of genetics when
discussing disorders of the auditory system due to the fact that many conditions
have strong genetic associations. Although
the purpose of this book is not to provide
the reader with a comprehensive coverage
of the genetic disorders that can result in
hearing loss, we felt that we could not
write a book on auditory disorders without dedicating some time to a review of
basic genetic principles and disorders. It
is beyond the scope of this book to discuss
these topics in great depth; however, we
provide the reader with some of the more
critical concepts associated with genetics,
along with a brief overview of the more
common genetically based auditory disorders. For those interested in learning
more about these topics, the following
resources are recommended:
➤ GeneReviews
➤ Genetics, Embryology, and Development
of Auditory and Vestibular Systems
(Jones & Jones, 2011)
➤ Genetics Home Reference: Your Guide to
Understanding Genetic Conditions (U.S.
National Library of Medicine, 2019l)
➤ Hereditary Hearing Loss and Deafness
Overview (Shearer, Hildebrand, &
Smith, 2017)
➤ Hereditary Hearing Loss and Its
Syndromes, Third Edition (Toriello &
Smith, 2013)
➤ Hereditary Hearing Loss Homepage (Van
Camp & Smith, 2019)
➤ Medical Genetics: Its Applications
to Speech, Hearing, and Craniofacial
Disorders (Robin, 2008)
®
(Adam et al., 1993–2019)
genetics oveRview
The typical human being has 23 pairs of
chromosomes, including 22 pairs of autosomes and a pair of sex chromosomes
(i.e., XX in females and XY in males).
413
414 Disorders of the Auditory System
https://t.me/medicina_free
These chromosomes contain genetic
material composed of deoxyribonucleic
acid (DNA) that is arranged on chromosomes in units called genes. DNA is inherited from one’s parents and is composed
of four chemical bases or nucleotides.
A nucleotide is a molecule that consists
of a nitrogen-containing base (adenine,
guanine, thymine, or cytosine in DNA
and adenine, guanine, uracil, or cytosine
in RNA), a phosphate group, and a sugar
(deoxyribose in DNA and ribose in RNA).
These nucleotides are strung together
in sequences on strands. There are two
strands of DNA nucleotides that bond
together to form a double helix. The bond
between these two strands is created by
the pairing of adenine with thymine and
guanine with cytosine.
Genes are composed of sequences of
DNA that contain the “genetic instructions” for creating proteins. There are two
copies of each gene, called alleles, with
one allele located on each member of the
chromosome pair. The genes carry the data
(i.e., the DNA sequences) needed to make
the various proteins that play important
roles in the growth and development of
the various structures and characteristics
of the human body. This is accomplished
via the processes of transcription and
translation. Transcription is the process
by which a complementary ribonucleic
acid (RNA) copy of a DNA sequence is
created (commonly referred to as messenger RNA or mRNA). This differs from
translation, where short strands of transfer RNA (tRNA) nucleotides (carrying
amino acids) pair with the corresponding
mRNA bases that have traveled from the
cell nucleus to the cell’s cytoplasm. The
end result of these processes is the decoding of the genetic code and the assemblage of a protein with a specific amino
acid sequence. There are several hundred
of these proteins that result from these
processes that are essential for the normal
formation and functioning of the auditory
system.
Changes may occur in the DNA
material of the genes (called mutations)
for a variety of reasons. If such changes
occur, they may result in alterations in
the end products of the genes (i.e., their
proteins). In turn, abnormalities in the
specific human growth or development
processes in which these proteins are
involved are likely to occur. Several types
of gene mutations can occur, including
nucleotide substitutions, deletions, and
insertions. A comprehensive discussion
of gene mutations is beyond the scope of
this chapter. The reader interested in additional information on gene mutations is
encouraged to access the resources listed
previously as well as a basic text addressing the principles of genetics (e.g., Lewis,
2018; Read & Donnai, 2015).
The inheritance of a disorder can be
caused by a single gene mutation or by
more than one gene mutation, as in the
case of digenic inheritance or modifier
genes. There are two types of inheritance
patterns: monogenic inheritance (includes
Mendelian inheritance) and complex or
multifactorial inheritance. When discussing monogenic inheritance patterns
related to hereditary hearing loss, there
are three patterns of inheritance that
are commonly discussed: (1) autosomal
recessive, (2) autosomal dominant, and
(3) X-linked. The location of the gene (i.e.,
on either an autosome or the sex-linked X
chromosome) and the number of mutated
alleles (one or two) will determine the
exact pattern of inheritance.
An important concept when one is
discussing monogenic inheritance patterns is that of zygosity, which refers to the
similarity of the gene’s two alleles. If the
9. Hereditary and Congenital Hearing Loss 415
https://t.me/medicina_free
two alleles of a single gene are identical,
they are said to be homozygous, whereas
if one of the alleles is a wild-type (or normal) allele and the other is mutated, they
are referred to as being heterozygous. If
both alleles of a gene are affected but by
different mutations, then the term compound heterozygous is used. The term
hemizygous is used to refer to the condition where only one allele is present, as
would be the case in sex-linked genes
where only one X chromosome is inherited (e.g., XY).
An additional monogenic inheritance
pattern sometimes seen in families with
hearing loss is the mitochondrial inheritance pattern. This inheritance pattern is
not as common as the other inheritance
patterns. It is unique in that the inherited
trait or characteristic can only be passed
by a mother to her child through her mitochondrial DNA (mtDNA).
When an individual is seen for
genetic evaluation, a geneticist or genetic
counselor will draw a pictorial representation of the family called a pedigree, which
includes the history of the family and the
occurrence of a specific disorder or syndrome within the family. The individual
who first brought the disorder or syndrome to medical attention is called the
proband, and this individual is typically
indicated in the pedigree by the presence
of an arrow. The various symbols used
in drawing a pedigree are shown in Figure 9–1, and these will be used in the pedigrees included in this chapter.
ual to have the disorder or syndrome. If
both parents have an autosomal recessive
disorder, then the offspring will inevitably
inherit the disorder as the offspring will
receive a mutated allele from each parent.
However, if both parents are heterozygotes
(i.e., they each have one mutated allele
and one nonmutated or wild-type allele),
the offspring may or may not inherit the
disorder depending on the specific allele
received from each parent as depicted in
Figure 9–2. In the latter scenario, neither
parent will manifest the disorder or condition, but both will be carriers of the trait
that then can be passed down to their offspring. In such a situation, each parent has
a 50% chance of passing a mutated allele
to their offspring, and as such, there is a
25% chance of having an offspring with
the disorder or syndrome, a 50% chance
of having an offspring who does not have
the disorder or condition but who would
be a carrier (i.e., the offspring would have
one mutated allele), and a 25% chance of
having an offspring who would neither
be a carrier nor have the disorder or syndrome. The same probability exists for
every pregnancy and does not change
as the number of pregnancies increases.
Consanguinity (i.e., parents related by
descent) significantly increases the chance
that two parents will be carriers for the
same mutated recessive gene that they
inherited from their common ancestors.
Figure 9–3 shows an example of a pedigree
that might be observed when there is an
autosomal recessive inheritance pattern.
Autosomal Recessive
Inheritance Pattern
In the autosomal recessive inheritance
pattern, both autosomal gene alleles must
have a mutation in order for the individ-
Autosomal Dominant
Inheritance Pattern
In the autosomal dominant inheritance
pattern, the inheritance of one mutated
allele is sufficient to cause a disorder or
416 Disorders of the Auditory System
https://t.me/medicina_free
Figure 9–1. The key to reading symbols of a pedigree.
Figure 9–2. Inheritance pattern for autosomal recessive conditions.
https://t.me/medicina_free
417
Figure 9–3.
Pedigree showing
autosomal recessive inheritance.
Note: the shaded
symbols represent
individuals in the
family tree with
the condition and
the arrow indicates
the proband.
418 Disorders of the Auditory System
https://t.me/medicina_free
syndrome (Figure 9–4). With every pregnancy, there is a 50% chance for a parent
with a specific disorder or condition to
pass the mutated allele to his or her offspring. If the mutated allele is passed to
the offspring, he or she will have the same
condition or syndrome as the affected parent. Here, unlike in the case of autosomal
recessive inheritance, many individuals
in different generations of the family may
have the disorder or syndrome; however,
the severity and the age of onset of the
condition may vary among these individuals. This phenomenon is called variable
expression and refers to the range in phe-
notype
that a particular genotype might
cause (Welch, 2006). A phenotype is the
clinical presentation or observable characteristics that result from the expression
of a particular genotype (i.e., the constitution of a set of alleles present at one or
more sites). For example, the same gene
mutation may result in varying degrees
of hearing loss within a family, with some
individuals having profound hearing loss
while others experience milder forms of
hearing loss. Another phenomenon that
can be associated with autosomal dominant inheritance patterns is reduced penetrance. This refers to the likelihood that a
Figure 9–4. Inheritance pattern for autosomal dominant conditions.
9. Hereditary and Congenital Hearing Loss 419
https://t.me/medicina_free
particular genotype will be expressed as a
phenotype less than 100% of the time. For
example, if 75% of individuals with a particular mutation are deaf and the remainder have normal hearing, this mutation
is said to have reduced penetrance. Figure
9–5 provides an example of a pedigree
that might be observed when there is an
autosomal dominant inheritance pattern.
X-Linked Inheritance Pattern
The X-linked inheritance pattern refers to
the mode of transmission of genes on the
X chromosome. This is a unique inheritance pattern as females have two X chromosomes (XX), whereas males have one X
and one Y chromosome (XY), and most of
the X chromosome genes do not have corresponding alleles on the Y chromosome.
As a result, if a male has a mutation in a
gene on the X chromosome, he will have
the condition or disorder associated with
that mutation because he only has the
one mutated allele. Females, on the other
hand, will not typically have the condition or disorder because they have one
mutated allele and one wild-type allele.
Figure 9–6 shows the inheritance pattern
for a recessive X-linked disorder with a
maternal carrier. In this inheritance pattern, there is a 25% chance that the couple
will have a male offspring with the disorder or syndrome, a 25% chance that
the offspring will be an unaffected male,
a 25% chance that the offspring will be
an unaffected female, and a 25% chance
that the offspring will be an unaffected
female who is a carrier for the condition.
Figure 9–7 depicts a representative pedigree for a family with this type of X-linked
recessive trait. The previous discussion
addresses the mode of inheritance with
a maternal carrier; however, an X-linked
recessive disorder or condition can also
be inherited paternally. If a male with the
disorder or condition mates with a female
with two wild-type (normal) alleles, then
none of the male offspring will be affected,
Figure 9–5. Pedigree showing autosomal dominant inheritance. Note: the
shaded symbols represent individuals in the family tree with the condition
and the arrow indicates the proband.
420 Disorders of the Auditory System
https://t.me/medicina_free
Figure 9–6. Inheritance pattern for X-linked recessive conditions.
but all of the females will be carriers who
may or may not show milder manifestations of the disorder.
Mitochondrial Inheritance
Although most of the DNA in humans is
located in the nucleus, a small amount is
located in the energy producing organelles called mitochondria. Humans obtain
their mitochondrial DNA from their
mothers due to the fact that egg cells contain mitochondria and sperm cells do not.
Hence, any mutations in the mtDNA are
passed from the mother to all of her children, both males and females. Figure 9–8
provides an example of a pedigree that
might be observed when there is a mitochondrial inheritance pattern.
Multifactorial Traits
For many disorders and conditions that
result in hearing loss, the cause can be
multifactorial (i.e., there can be an intricate interaction between genes and the
9. Hereditary and Congenital Hearing Loss 421
https://t.me/medicina_free
Figure 9–7. Pedigree showing X-linked recessive inheritance. Note: the
shaded symbols represent individuals in the family tree with the condition
and the arrow indicates the proband.
Figure 9–8. Pedigree showing mitochondrial trait inheritance. Note: the shaded
symbols represent individuals in the family tree with the condition and the arrow indicates
the proband.
Соседние файлы в папке Библиотека им академика М.И. Перельмана