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LESSON 149

Common syndromes

Year 2
Spring semester
Genetic Hearing Loss
Genetics
Duration: 11:25

We explain four important syndromes with hearing loss: Usher syndrome with retinitis pigmentosa, Pendred syndrome with thyroid enlargement and an enlarged vestibular aqueduct, Waardenburg syndrome with its pigment findings, and Alport syndrome with kidney involvement. We cover their types, inheritance patterns, audiological features and the audiologist's role in referral.

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Hello, and welcome to the AIHEAR Audiology Academy.
In this lesson, we learn about four important syndromes that come with hearing loss.
We will cover the findings, inheritance and audiological features of Usher, Pendred, Waardenburg and Alport syndromes.
In syndromic loss, findings in other organs accompany the hearing loss; these findings are the key to diagnosis.
In Usher syndrome, the hearing loss comes with progressive vision loss.
In Pendred syndrome, the thyroid gland enlarges.
In Waardenburg syndrome, pigment changes are seen in the hair, skin and eyes.
In Alport syndrome, kidney disease is at the center of the picture.
Usher syndrome is an inherited syndrome in which sensorineural hearing loss is accompanied by retinitis pigmentosa.
Retinitis pigmentosa is an eye disease in which the light-sensing cells of the retina are gradually lost.
The first symptom is usually night blindness; then the visual field narrows from the edges and tunnel vision develops.
Usher syndrome is inherited in an autosomal recessive pattern and is the most common cause of inherited deafblindness.
Its frequency varies between populations; it is reported at about four to seventeen per hundred thousand.
The hearing loss is found early through screening, but because vision symptoms begin years later, the syndrome may be recognized late.
Usher syndrome is divided clinically into three types.
In type 1, the loss is congenital and profound, and vestibular function is also markedly reduced.
These children usually start walking late; vision symptoms mostly appear in the first decade.
Type 2 is the most common type; the loss is congenital, moderate to severe and sloping toward the high frequencies.
In type 2, balance is normal; vision symptoms usually begin in adolescence or later.
In type 3, the loss begins after birth and progresses; balance and vision findings vary from person to person.
Most Usher genes code for proteins involved in the structure and development of the hair cell stereocilia bundle.
Cadherin 23 and protocadherin 15, which form the tip link, are among the proteins linked to type 1 Usher.
These proteins keep the bundle neatly arranged and allow the transduction channels to open.
Similar proteins work in the light-sensing cells of the retina, which is why hearing and vision are affected together.
Some changes in the same genes, however, can cause hearing loss alone, that is, nonsyndromic loss.
One way to recognize type 1 Usher early is to ask about motor development in a child with severe loss.
Delays in head control, sitting and walking can suggest vestibular loss; vestibular tests can show this.
Complaints such as falling in the dark, struggling on stairs in the evening or often bumping into things call for an eye exam.
The definitive diagnosis is made with an ophthalmologist's evaluation, electrical tests of the retina and genetic testing.
Early diagnosis gives the family the chance to make timely decisions about communication approach and cochlear implants.
In Usher syndrome, hearing rehabilitation is planned with the expectation that vision will also decline over time.
In type 1, because of the profound loss, a cochlear implant often comes up early.
In type 2, hearing aids usually give good benefit; settings are updated with regular monitoring.
As vision declines, hearing becomes even more important for communication and for sensing the surroundings.
This is why it matters that the ophthalmologist, the audiologist and the education team work together.
We saw Pendred syndrome in the lesson on enlarged vestibular aqueduct; let us briefly recall it.
Pendred syndrome is an autosomal recessive syndrome caused by the SLC26A4 gene.
The sensorineural loss is often severe, and it can fluctuate and progress.
Imaging shows an enlarged vestibular aqueduct and sometimes structural differences of the cochlea.
Thyroid enlargement usually appears in late childhood or adolescence; the physician plans the thyroid evaluation.
Waardenburg syndrome is a syndrome in which hearing loss is accompanied by pigment changes in the hair, skin and eyes.
The problem lies in the development of neural crest cells, which in the embryo become pigment cells and some inner ear cells.
A white tuft of hair at the front, called a white forelock, is a typical finding.
Two eyes of different colors, or two colors in one eye, is called iris heterochromia.
Early graying of the hair and light-colored patches on the skin can also be seen.
The findings vary greatly from person to person, even within one family; some individuals have only one finding.
Waardenburg syndrome is divided into four types.
In type 1, the inner corners of the eyes are displaced outward; this is called dystopia canthorum.
In type 1, the most commonly responsible gene is PAX3.
Type 2 has no dystopia canthorum; hearing loss is more common in this type.
In type 3, muscle and joint anomalies of the arm and hand are added to the type 1 findings.
In type 4, it is accompanied by Hirschsprung disease, in which nerve cells are missing from the large intestine.
In Waardenburg syndrome, the loss can be unilateral or bilateral, and its degree varies widely.
In this example, the right ear has a profound loss, while the left ear has normal hearing.
In the same family, one person may have severe loss and another normal hearing; this is called variable expressivity.
So the hearing of each family member should be evaluated separately.
The loss is usually congenital and often does not progress; even so, regular monitoring is done.
Alport syndrome is an inherited syndrome in which kidney disease is accompanied by hearing loss and eye findings.
The cause is changes in the genes that code for type four collagen, a structural part of basement membranes.
The first kidney finding is usually blood in the urine; over time, the disease can progress to kidney failure.
Most cases are X-linked, so males are affected more severely and earlier.
There are also autosomal recessive and, less often, autosomal dominant forms.
In the eye, a forward bulging of the front surface of the lens and spots on the retina can be seen.
In Alport syndrome, hearing loss is not present at birth; in X-linked males, it usually begins in late childhood.
The loss is bilateral and sensorineural; it usually starts at the high frequencies and progresses over the years.
In this example, both ears show a symmetric loss that increases toward the high frequencies.
The loss is thought to be linked to involvement of basement membrane structures in the cochlea.
In the X-linked type, early-onset hearing loss is seen as a clue that kidney disease may progress faster.
This is why regular hearing monitoring is recommended for children diagnosed with Alport syndrome.
A clinical tip: add a few short questions to the history of every child with hearing loss.
Is there trouble seeing in the dark, or a white forelock or different-colored eyes in the family?
Is there a family history of kidney disease or dialysis at a young age, or thyroid enlargement?
The answers to these questions directly guide the physician's decision on genetic and systemic evaluation.
Now let us see the four syndromes side by side.
Usher is autosomal recessive; the hearing loss comes with retinitis pigmentosa.
Pendred is also autosomal recessive; it comes with goiter and an enlarged vestibular aqueduct.
Waardenburg is usually dominant and is recognized by its pigment findings.
Alport is usually X-linked; the hearing loss begins after birth and comes with kidney disease.
The audiologist is often one of the first to notice syndromic clues.
They clearly record the findings they observe beyond hearing and the family history in the report.
Through the physician, they arrange referral for genetic evaluation and to the needed specialists.
In syndromes where progressive loss is expected, they monitor hearing regularly and update rehabilitation accordingly.
Diagnosis and treatment decisions belong to the physician and the relevant specialists; the audiologist is a constant part of this team.
In Usher syndrome, the hearing loss comes with retinitis pigmentosa; there are three clinical types.
Pendred syndrome shows an enlarged vestibular aqueduct and goiter in adolescence.
Waardenburg syndrome is recognized by a white forelock, heterochromia and variable hearing loss.
In Alport syndrome, kidney disease is accompanied by a progressive sensorineural loss that begins after birth.
Test yourself: In a child with congenital profound loss who walks late, which syndrome should be considered?
The correct answer is A: type 1 Usher syndrome.
In this type, vestibular loss delays motor development, while vision symptoms begin years later.
In the next lesson, we will look at other important syndromes linked to hearing loss and their audiological monitoring.
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Prerequisites

LESSON 148 GJB2 and connexin 26

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