Usher Syndrome

Erica Choi

History of Usher Syndrome

• 1860, German von Graeffe and Liebrreich detect pigmentary changes in the retinas of deaf children

• 1914 – C. H. Usher (for whom the syndrome is named after) published case studies of affected people and stressed the family link

• Since then, researchers have been working to find at least eleven different genes involved, and develop a better understanding of the syndrome

• Currently researchers are trying to utilize dietary supplements to slow the progression of RP

What causes Usher Syndrome?

• Usher Syndrome is caused by an autosomal recessive disorder

• 10 genes are generally associated with Usher Syndrome, one or more of which can be responsible

• In order for an individual to be born with Usher Syndrome, both of his/ her parents must be a carrier of the identical gene mutation – (i.e. carriers of two differing Usher genes will NOT

produce children with Usher phenotypes, only more carriers)

Genes Linked to Usher Syndrome

Acquiring Usher Syndrome

• 25% chance IF both parents are carriers of the same gene disorder

• In the U.S., about 4 babies in every 100,000 births

• Responsible for 6% of all deaf children and another 6% of all blind children

General Symptoms

• Hearing loss eventually leading to deafness• Eye disorder eventually leading to complete

blindness– initially in terms of night blindness, loss of peripheral

vision and, eventually• Though rare, it is the most frequent cause of

deaf-blindness in humans

Retinis Pigmentosa (RP)

Eye affected by RP A Normal Eye

• RP is a degenerative disease leading to eventual blindness (the onset and rate of blinding vary)

• Characterized by pale optic nerve, thin vessels, and bone spicules (shown by the double white arrows)

What causes RP?

• Genetic malformation causes the absence of one or more vital proteins for retinal survival – Explains why affected children can see normally at

first but experience night-blindness, loss of peripheral vision, and eventual blindness as the photoreceptors gradually die.

– Depending on the protein that is absent, affected people may maintain a small pinhole of usable vision well into midlife

Usher Syndrome Type I

• Profoundly deaf at birth; will obtain no benefits from hearing aids due to the severity of the issue

• Early and rapid development of visual problems, usually by their tenth year

• Severe balance problems; children often can’t sit or walk independently

• Need to be diagnosed early to take full advantage of intervention methods before the phenotype is completely expressed

Usher Syndrome Type II

• Moderate to severe hearing loss, normal balance• Can benefit from hearing aids• Onset of visual issues slower than those with

Type I (RP not apparent until well into their teens)

Usher Syndrome Type III

• Normal hearing at birth, and the rate of deterioration vary greatly among individuals

• Generally acquire hearing aids by mid- to late-adulthood

• Night blindness begins sometime during puberty, and by mid-life, the individual is generally legally blind

• Near-normal balance (may develop balance issues later in life)

Classification of the Different Types

Clinical Type Subtype Gene/Protein Hearing Loss VestibularNight Blindness Onset

  I Ib MYO7A Profound Absent 1st decade

  Ic Harmonin Profound Absent 1st decade

  Id CDH23 Profound Absent 1st decade

  If PCDH15 Profound Absent 1st decade

  Ig SANS Profound Absent 1st decade

  II IIa UsherinModerate/ Progressive?

Normal 2nd decade

  IIc VLGR1Sloping Moderate

Normal 2nd decade

  IId WhirlinSloping Moderate

Normal 2nd decade

  III IIIc Clarin-1 Progressive Variable 2nd decade

Identification of the Disease

• Direct examination of the retina, where an ophthalmologist will find attenuated blood vessels, a waxy pallor, and clumps of dead retinal cells called bone spicules

• Electroretinogram (ERG), an evoked response from the rods and cones of the retinate that is reduced when Usher syndrome is present

• Genetic testing• Study of behavioral patterns (objective measures

of the audiologist)

Treatment

• Currently, no fundamental cure is available• Treatment can include: hearing aids, cochlear

implants, learning American Sign Language, orientation training, etc

• Some believe that vitamin A palmitate may slow the worsening of symptoms for individuals with Type II and III – This belief is based on researches conducted by the

National Eye Institute and the Foundation for Fighting Blindness

Bioethical Concerns

• To enhance our understanding of Usher syndrome, genetic testing is inevitable

• This presents an ethical dilemma as many worry that genetic testing will lead to some kind of a discrimination against the carrier of the “inferior” gene– Ex: a health insurance company refuses to accept a

person based on their genes

• Genetic testing may also alter humans’ natural reproductive patterns to produce better offspring, an idea unacceptable to many religious groups

Bibliography

• CAUSE Project. "Usher Syndrome - A Brief History." Usher Syndrome - A Brief History. European Commission, n.d. Web. 18 Feb. 2013. <http://www.deafblindinternational.org/cause_fact2.html>.

• Christenson, Shaun. "The Ethical Considerations of Genetic Screening." The Ethical Considerations of Genetic Screening. North Dakota State University, 1998. Web. 18 Feb. 2013. <http://www.ndsu.edu/pubweb/~mcclean/plsc431/students98/christenson.htm>

• National Eye Institute. "What Is Usher Syndrome?" Usher Syndrome Home Page. USAgov.com, n.d. Web. 08 Feb. 2013. <http://www.ushersyndrome.nih.gov/index.html>

• Wallber, Josara. "Understanding Usher Syndrome." Understanding Usher Syndrome. American Speech-Language-Hearing Association, n.d. Web. 09 Feb. 2013. <http://www.asha.org/aud/articles/UsherSyndrome/>.