Professional Documents
Culture Documents
and Deafness
Hereditary Blindness
and Deafness
The Race for Sight
and Sound
Todd T. Eckdahl
Hereditary Blindness and Deafness: The Race for Sight and Sound
Copyright Momentum Press, LLC, 2017.
DOI: 10.5643/9781944749743
10987654321
Keywords
autosomal dominant, autosomal recessive, blindness, deafness, genetic
disease, hearing loss, hereditary blindness, hereditary deafness, nonsyn-
dromic deafness, sex-linked, X-linked, syndromic deafness, Y-linked,
vision loss
Contents
Acknowledgmentsix
Introductionxi
Chapter 1 Symptoms and Diagnosis1
Chapter 2 Causes and Contributing Factors17
Chapter 3 Treatment and Therapy45
Chapter 4 Future Prospects51
Conclusion59
Glossary61
Bibliography67
Index69
Acknowledgments
I am grateful to my friend Malcolm Campbell for encouraging me to take
a leap of faith for this project, and for several others that have shaped my
career as a science educator. I value Malcolm as a teaching and research
collaborator, and I am proud of the positive impact that we have made
together on science education and the improvement of science literacy. I
am also grateful for the cheerful and professional support I received from
the publishing team at Momentum Press.
This book would not have been possible without the support of my
wife Patty Eckdahl. She understands my passion for science and science
education and helps me to channel it in ways that benefit students and
others around me. I also appreciate the support and encouragement that
my parents, Tom and Bonnie Eckdahl, gave me in the pursuit of an edu-
cation that would give me the privilege of sharing my love of DNA and
genetics with undergraduate students and everyone else I meet.
I am grateful to my undergraduate genetics professor at the University
of Minnesota, Duluth, Stephen Hedman, for helping me to understand
that I could pursue my love of genetics in graduate school. Thanks to
John Anderson at Purdue University, who taught me to conduct molecu-
lar genetics research and to value undergraduate education. I appreciate
the supportive environment that Missouri Western State University has
provided me, and I am grateful to my mentors in the Missouri Western
Biology Department, Rich Crumley, Bill Andresen, John Rushin, and
Dave Ashley, who helped me to learn how to engage students in the class-
room and the research lab. I appreciate the many students that I have
worked with in class and collaborated with on research projects outside
of class. I take pride in the contributions that my former students have
already made, and will continue to make, to society.
Introduction
Kent Desormeaux is a jockey who won over 5,700 thoroughbred horse
races and set the U.S. record in 1989 for most wins in a year with 598.
Kent won the Kentucky Derby three times, the Preakness Stakes three
times, and the Belmont Stakes once. In 2008, he had a chance to win
them all in the same year, which is called the Triple Crown. He had
already won the Kentucky Derby and the Preakness as his 9-year-old
son Jacob cheered him on at the Belmont Stakes. As his father raced for
the Triple Crown, Jacob was in his own race for sight and sound. Jacob
could not hear the thundering hooves heading down the home stretch
and strained through his glasses to see his father lose his bid for the Triple
Crown because Jacob was born with Usher syndrome, a hereditary dis-
ease that caused him to be profoundly deaf and to slowly lose his sight
by adulthood. Jacob has since gained ground in his race for sound with
cochlear implants that allow him to hear, but he is losing his race for sight
and is becoming blind.
More than 350 million people worldwide have moderate to severe
hearing loss or are profoundly deaf. About 1 in 1,000 babies is born
with moderate to profound hearing loss, and about half of the cases have
genetic causes, with the other half being due to nongenetic factors such as
maternal infections, drug or alcohol use during pregnancy, or premature
birth. About 30 percent of hereditary hearing loss is syndromic hearing
loss, during which partial or total hearing loss is caused by malformations
of the external ear and is accompanied by problems with other organ
systems. There are over 400 genetic diseases that cause syndromic deaf-
ness. Usher syndrome is an example of syndromic deafness because it
causes mild to profound hearing loss and a progressive loss of vision from
retinitis pigmentosa. Other examples of syndromic deafness are Alport
syndrome, which causes mild to profound hearing loss, kidney disease,
and vision loss, and Waardenburg syndrome, which causes mild to pro-
found hearing loss and developmental abnormalities. About 70 percent of
hereditary hearing loss is nonsyndromic hearing loss, which is a partial
xii INTRODUCTION
This chapter describes examples that illustrate the large diversity of ge-
netic diseases that affect vision and hearing. It presents the symptoms and
diagnosis of nonsyndromic hearing loss and three examples of syndromic
deafness. It illustrates hereditary blindness with information about the
symptoms and diagnosis of seven hereditary eye diseases, chosen for their
prevalence and their varied effects on the visual system. Throughout this
chapter and book, the terms hearing loss and vision loss will be used to
refer to the effects of diseases that are not complete deafness or blindness.
signals of nerve impulses. The cochlea is also part of the vestibular sys-
tem, which provides overall body balance and spatial orientation. The
vestibulocochlear nerve sends impulses from the inner ear to the brain,
which processes them as sounds that we perceive. Hearing occurs either
through air conduction or bone conduction. Air conduction occurs when
sound waves that enter the ear canal cause the eardrum to vibrate, which
leads to vibration of the bones of the middle ear. During bone conduc-
tion, sound waves that travel through the bones of the skull are detected
by the cochlea. Bone conduction is also facilitated by the mastoid bone
located behind the ear.
The perceived loudness of a sound depends on the ability to hear and
on the intensity of the sound. The decibel (dB) is a unit named after Al-
exander Graham Bell that measures the relative intensity of sounds, and it
is defined as 10 times the logarithm of the ratio of the intensity of a given
sound to the standard threshold of hearing, which is set as the minimum
intensity that most people can hear. A value of 0 dB does not mean there
is no sound, but that the sound pressure is equal to the standard. The
standard threshold of hearing causes a pressure change that is about one
billionth of the standard pressure of the atmosphere, which illustrates the
sensitivity of human hearing. Because the decibel scale is logarithmic,
there is a 10-fold increase or decrease in intensity between sounds that
differ by 10 dB, a 100-fold increase or decrease for 20 dB, a 1,000-fold
increase or decrease for 30 dB, and so on. For perspective, a whisper is
about 20 dB, a conversational level is about 60 dB, train whistles are about
100 dB, and a very loud rock concert can be over 120 dB. The hearing
threshold is the minimum intensity of sound that a person can hear. The
normal hearing threshold ranges from 10 dB, which means that a person
can hear a sound that is one-tenth the intensity of the standard, to 15 dB,
which is an intensity that is about 32 times higher than the standard. As
shown in Table 1.1, the severity of hearing loss is categorized from mild
to profound. Adults with hearing loss greater than 40 dB and children
with hearing loss greater than 30 dB are said to have disabling hearing
loss. Total deafness occurs when a person has profound hearing loss or
cannot hear sound at all, regardless of its intensity.
There are about 360 million people worldwide who have disabling
hearing loss, which is about 5 percent of all people. About 10 percent of
Symptoms and Diagnosis 3
people with disabling hearing loss are children, and one-third are 65 years
of age or older. Data from the United States demonstrate that the preva-
lence of hearing loss increases with age. Two percent of adults aged 45 to
54 have hearing loss, compared to 8.5 percent of those aged 55 to 64 years,
25 percent of those aged 65 to 74 years, and 50 percent among people
75 years or older.
Hearing loss can be congenital, which means that it is present at birth,
or it can develop later in life, during childhood or adulthood. Hearing
loss can also be hereditary or acquired. Acquired hearing loss can occur
at any stage of life, including embryonic and fetal development. Infec-
tions during pregnancy such as syphilis, rubella, herpes, toxoplasmosis,
or cytomegalovirus are responsible for about 30 percent of congenital
acquired hearing loss. The risk of congenital hearing loss is also higher
among infants that have low birth weight, jaundice, or oxygen depriva-
tion. Acquired hearing loss can occur in infants, children, and adults from
infectious diseases such as encephalitis, measles, mumps, chicken pox,
meningitis, or the flu. Trauma to the head or the ear, repeated exposure to
occupational or recreational loud noise, and side effects of some medica-
tions can also cause acquired hearing loss.
Hereditary hearing loss is categorized as syndromic or nonsyndromic.
Nonsyndromic hearing loss is a partial or complete loss of hearing that
is not associated with symptoms involving other parts of the body, and
it accounts for about 70 percent of the cases of inherited hearing loss.
Nonsyndromic hearing loss can be categorized according to four patterns
of inheritance (Table 1.2), which are explained in Chapter 2. Within each
of these categories, the age of onset, progression, and severity of hearing
4 HEREDITARY BLINDNESS AND DEAFNESS
the ability of the patient to hear a vibrating tuning fork pressed against
the bone behind their ear to their ability to hear it when it is placed just
outside their ear. For a patient with conductive hearing loss, the ringing
sound is transmitted better through their bones than through the struc-
tures of their ear. A patient with sensorineural hearing loss cannot convert
either source of sound vibrations into a nerve signal to the brain.
Whereas the diagnosis of nonsyndromic hearing loss depends solely
on clinical assessments of hearing loss and the functions of the auditory
system, the diagnosis of syndromic hearing loss involves evaluation of
other body systems. The diagnosis of Alport syndrome might begin with
the detection of blood in the urine of an infant. More commonly, the
progressive kidney dysfunction associated with the disorder is detected by
blood discoloration in the urine that occurs in childhood or adolescence.
Clinical laboratory analysis is used to confirm the presence of blood and
abnormally high protein levels in the urine, which are indirect measures of
kidney disease. Microscopic examination of a kidney biopsy provides direct
evidence of characteristic changes in the structure of the kidney in support
of a diagnosis of Alport syndrome, and is used to exclude other causes of
kidney disease. A clinical ear examination is also used to diagnosis Alport
syndrome and to rule out other causes of hearing loss such as damage to
the eardrum or infection of the middle ear. Audiometry is used to m easure
the hearing threshold for a series of frequencies ranging from low to high.
The onset of hearing loss for patients with Alport syndrome involves a
reduction in their ability to hear high-frequency sounds. Aconductive
hearing test can also be used to distinguish the sensorineural hearing loss
associated with Alport syndrome from conductive hearing loss. Because
Alport syndrome is hereditary, family history can contribute significantly
to its diagnosis, which can be confirmed by genetic testing.
Waardenburg syndrome causes hearing loss that ranges from mild to
profound, and can be present at birth or develop later. Audiometry is
used to measure the onset and severity of the hearing loss. A diagnosis
of Waardenburg syndrome can distinguish among the four types of the
syndrome that occur, the two most common of which are type I and
type II. Because the characteristic feature of wide-set eyes is found with
type I Waardenburg syndrome but not type II, careful measurements of
the angle of the eyes and the distance between the pupils are useful in a
Symptoms and Diagnosis 9
contain proteins that make the cells transparent. Small muscles attached
to the lens can change its optical properties by making it thicker or thin-
ner, thereby focusing the image on the retina at the back of the eye. The
retina contains photoreceptor cells called rods and cones that convert
light information into electrical signals that are conveyed by the optic
nerve to the brain. Rods are specialized for distinguishing black and white
and for detecting low light, whereas cones are specialized for various col-
ors of light. The fluid in the eye is called the aqueous humor, and its level
is maintained by a filtration system (trabecular meshwork) located at the
angle of the eye where the pigmented iris meets the cornea. Human vision
is so complex that it is not surprising to learn the variety of ways that it
can be compromised. Injuries, acquired diseases, and inherited diseases
can cause moderate or severe visual impairment, including blindness.
The most common cause of partial or total blindness in one eye is
amblyopia, and it affects about 3 percent of children worldwide under the
age of 6 years (Table 1.3). Amblyopia is commonly called lazy eye because
one eye makes a much smaller contribution to vision than the other eye, but
this term is misleading because it implies that the problem would go away
with better effort and that the eye is solely to blame for it. The problem
is poor communication between the eye and the brain, and it starts when
the brain receives better visual input from one eye than the other because
of nearsightedness, childhood cataracts, or permanently crossed eyes. As the
brain continues to ignore input from the weaker eye, the function of the eye
gradually deteriorates from lack of use. The symptoms of amblyopia include
blurred vision, double vision, and poor depth perception. Amblyopia often
causes the eyes to move independently of one another, instead of coordinately.
A cataract occurs when the lens of an eye becomes opaque to visible
light. The resulting blurred and dulled vision worsens over time as the
cataract worsens, and can lead to blindness. Cataracts cause sensitivity
to bright light, poor night vision, double vision, and frequent changes
in the prescription for corrective lenses. Eventually, a cataract causes the
lens to adopt a yellowish color that tints the visual image and makes it
difficult to identify shades of blue. A congenital cataract is either pres-
ent at birth or develops within the first year. Congenital cataracts occur
at a rate of about 3.5 in 10,000 births and account for between 5 and
20 percent of worldwide childhood blindness. Age-related cataracts
result from a progressive change in the lens over 45 or more years. This
form of cataracts is responsible for almost half of the cases of blindness
worldwide, and occurs in about 2.5 in every 1,000 people. (Table 1.3)
Cataracts can also be acquired by an eye injury, by exposure to radiation,
as a health complication of diabetes, or as a complication of eye surgery.
Color blindness is the inability to distinguish colors, and it takes
a variety of forms that differ in symptoms and severity. The three main
types of color blindness are red-green, blue-yellow, and total color blind-
ness. Color blindness ranges from subtle and often unnoticed differences
in color perception to the complete inability to distinguish colors. The
most common form of color blindness is red-green color blindness, and
because it is caused by a gene on a sex chromosome, it affects males more
often than females, with a worldwide prevalence of about 80 males and
5 females in every 1,000 births (Table 1.3). The symptoms of red-green
color blindness depend on whether there is partial or total loss of the
perception of red or green. Most people with red-green color blindness
have partial loss of green perception, which makes yellow and green colors
appear redder to them, and makes it hard for them to distinguish violet
and blue. These are mild symptoms that do not have a large impact on
daily life. The two types of red-green color blindness that are associated
12 HEREDITARY BLINDNESS AND DEAFNESS
with the complete failure to perceive red or green have more substantial
symptoms. Blue-yellow color blindness affects males and females equally.
It can be caused by a diminished ability to detect blue light, which makes
blue appear to be greener, and makes it difficult to tell yellow and pink
apart. It can also be caused by the complete inability to perceive blue,
which makes blue appear to be green and yellow appear to be violet or
gray. Complete color blindness is the inability to detect at least two of
the three colors of red, green, and blue. People with this condition see
the world in shades of gray. Complete color blindness affects males and
females equally, and is extremely rare.
Corneal dystrophy refers to a collection of over 20 eye diseases that
cause the abnormal accumulation of foreign material such as dust, dead
cells, and bacteria in one or more of the five tissue layers of the cornea. The
symptoms of corneal dystrophies accumulate gradually during the first 20
years of life, and their severity varies widely. Some people with corneal dys-
trophy are asymptomatic, whereas others have severe visual impairment, in-
cluding blindness. Many types of corneal dystrophy cause corneal erosion,
during which the attachment of the outermost layer of the cornea to the un-
derlying tissue is compromised. The symptoms of corneal erosion include
mild to severe eye pain, light sensitivity, blurred vision, watery eyes, and dry
eyes. Corneal dystrophies usually affect both eyes equally. The worldwide
prevalence of corneal dystrophy is about 9 in 10,000 births (Table 1.3).
Age-related macular degeneration is the deterioration of the macula,
a small patch of densely packed rods and cones at the center of the retina
that controls the sharpness of visual images and enables visual perception
of fine details. Age-related macular degeneration is the leading cause of vi-
sion loss among the elderly. Its prevalence in developed countries is about
5 in 10,000 people (Table 1.3), and is expected to increase as the propor-
tion of elderly people rises. About 90 percent of the cases of age-related
macular degeneration are of the dry type, associated with the accumula-
tion of yellowish deposits underneath the retina that cause gradual loss of
vision in both eyes. The remaining cases are of the wet type and are char-
acterized by the abnormal growth of blood vessels beneath the macula,
which leak blood and serum that cause blurry and distorted vision.
Another cause of hereditary blindness is retinitis pigmentosa, which is
a collection of diseases that are characterized by degeneration of the retina
Symptoms and Diagnosis 13
countries, routine eye tests are not usually given until the age of 5 years.
The American Optometric Association recommends a comprehensive eye
examination for children at the ages of 6 months and 3 years. In older
children and adults, amblyopia often goes unnoticed because the brain
and the stronger eye compensate for the weaker eye. The diagnosis of
amblyopia depends on detecting a difference in vision between the two
eyes, or poor vision in both eyes. In older children and adults, visual
acuity is usually measured with a Snellen chart containing progressively
smaller letters or with a chart containing symbols for those who cannot
read. Visual acuity is measured in an infant by covering one eye and ob-
serving how well the infant can follow an interesting moving object. If
monocular amblyopia is present, the infant might try to remove the patch
to better see the object or outwardly display their frustration. Treatments
for amblyopia are most effective if the diagnosis is made at an early age.
A diagnosis of congenital cataracts begins with a comprehensive eye
examination. A key test is to measure the response to red light, which
is reduced or absent in infants with congenital cataracts. The opacity
of the lens is also measured, and microscopic examination of the eye is
used to directly observe the location and severity of cataracts. If there is
a family history of cataracts, then it is reasonable to assign the cause of
congenital cataracts as hereditary. If not, additional tests are performed
to attribute congenital cataracts to environmental exposure, infectious
disease, a metabolic disorder, or a genetic syndrome. The diagnosis of
age-related cataracts begins with a standard eye exam and is often con-
firmed by an ophthalmologist. A Snellen chart test detects the effect of
cataracts on visual acuity, and examination of the lens with an ophthal-
moscope after pupil dilation enables direct observation of the size and
severity of cataracts.
Several tests are used to quickly diagnose color blindness. Historically,
the most commonly used test is the Ishihara Color Test, which uses a
series of 38 plates that are composed of circles of various sizes and col-
ors. Each plate has a number or a shape that can be perceived by those
who can distinguish colors, but not by those who have color blindness.
It is easy to find Ishihara Color Test plates online, and although these
can be used for initial testing, a definitive diagnosis should be made by
an ophthalmologist. The Cambridge Color Test is based on the same
Symptoms and Diagnosis 15
concept, but asks the patient to observe the orientation of the letter C.
Getting the correct answer depends on being able to make color distinc-
tions such as red versus green, or subtler distinctions such as violet versus
blue. Another test for color blindness, called the anomaloscope, presents
the patient with a circle formed by two different sources of light. The
patient is asked to adjust the brightness of the yellow light in the top half
of the circle and the proportion of red and green light in the bottom half of
the circle until the two halves appear to be the same shade and intensity
of yellow. People with color blindness adjust the anomaloscope differently
than people with normal vision. More specialized color blindness tests
have been developed to test graphic designers, photographers, or pilots
who depend on accurate color perception.
The diagnosis of corneal dystrophy begins with the observation that
the cornea has lost some or all of its transparency. Having a family history
of corneal disease contributes to the preliminary diagnosis. A definitive
diagnosis of corneal dystrophy is made by an ophthalmologist using a slit
lamp microscope to examine the cornea. A thin, bright sheet of light is
shined into the eye, and the ophthalmologist looks carefully at the nature
of the corneal defect to determine which of the over 20 forms of corneal
dystrophy is present.
Age-related macular degeneration can be detected during a regular eye
examination. Diagnosis of the dry form of macular degeneration requires
dilation of the pupils with eye drops and an ophthalmoscope to carefully
observe the retina at the back of the eye, looking for degradation of the
macula. The wet form of macular degeneration is diagnosed with more
specialized tests such as fluorescein angiography, which uses a fluores-
cent dye injected into the bloodstream to enable a detailed view of the
tiny blood vessels in the retina, and optical coherence tomography,
which can provide high-resolution images of the retina.
Retinitis pigmentosa can be diagnosed with clinical procedures that
are used during a comprehensive eye examination. An ophthalmologist
can use an electroretinogram to measure the ability of retinal rods and
cones to generate an electrical signal after receiving a light stimulus. The
visual field test presents objects to a patient with a fixed gaze in order to
map the visual field. Retinitis pigmentosa restricts the visual field in char-
acteristic ways that an ophthalmologist can recognize. Optical coherence
16 HEREDITARY BLINDNESS AND DEAFNESS
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