Genetic Hearing Loss Associated with Eye Disorders

Question 1

What is usher syndrome?

Answer 1

Deaf-blind disorder
Common among profoundly deaf community and deaf-blind community

Question 2

How is ushers inherited?

Answer 2

Autosomal recessive; consanguinity often reported
Multiple genes and multiple chromosomes involved
Most common AR syndromic hearing loss

Question 3

What do the genes involved in ushers do?

Answer 3

These genes have instructions for making proteins (e.g., myosin) that play important roles in the development and maintenance of hair cells
In the retina, these genes are involved in determining the structure and function of rods and cones
Most mutations responsible for Usher syndrome lead to loss of hair cells in the inner ear and gradual loss of rods and cones in retina

Question 4

What are some characteristic features of ushers?

Answer 4

Intellectual disability and psychosis are reported in many cases
Hearing loss can be mild to severe progressive SNHL
The most common symptoms are progressive hearing loss and blindness associated with retinitis pigmentosa (RP), which typically develops during the 2nd decade

Question 5

What is retenitis pigmentosa?

Answer 5

It is the scarring of the retinal pigment layer with uneven gathering of pigment into clusters
Regions initially affected are at the periphery of the retina and then progresses towards the macula or center

Question 6

What are the progressive loss of vision stages in ushers?

Answer 6

Difficulty seeing at night during their teen years
Progressing to tunnel vision
Progressing to blindness by 30 to 40 years old

Question 7

What are the different types of ushers?

Answer 7

Type I
Type II
Type III

Question 8

What is the rarest form of ushers?

Answer 8

Type III

Question 9

What are some characteristic features for type I of ushers?

Answer 9

Congenital severe-to-profound SNHL
Traditional amplification is ineffective
Abnormal vestibular function and gait ataxia
Delayed motor milestones

Question 10

What are some characteristic features for type II of ushers?

Answer 10

Congenital mild-to-severe SNHL
HAs are effective
Normal vestibular function

Question 11

What are some characteristic features for type III of ushers?

Answer 11

Progressive SNHL with progressive vestibular dysfunction
Possible founder effect in the Fins and Ashkenazi Jews

Question 12

What is the differential diagnosis for ushers?

Answer 12

Norrie syndrome and other disorders with retinitis pigmentosa and SNHL

Question 13

What are other major syndromes associated with RP and SNHL?

Answer 13

Hallgren syndrome
Cockayne syndrome
Alstrum syndrome
Refsum syndrome

Question 14

What is norrie syndrome?

Answer 14

Rare
Exact incidence unknown
Not associated with any specific racial or ethnic group
Visual problems, associated with SNHL and dementia

Question 15

What is the inheritance pattern of norrie syndrome?

Answer 15

X-linked recessive
Mutation believed to be deletion
The greater the deletion, the greater the severity of intellectual disability and other symptoms

Question 16

What are some characteristics of norrie syndrome?

Answer 16

Typical onset, is in the early 2nd decade
Most common cause of congenital retinal detachment
Congenital progressive blindness generally not caused by retinitis pigmentosa
Cataracts and atrophy of iris visible to even the casual observer
CNS involvement (Intellectual disability (low IQ), Seizures, Psychiatric disorders reported but not for all cases)

Question 17

What are the audiologic findings for norrie syndrome?

Answer 17

Progressive moderate to severe SNHL developing at about ~ 10 years in ~ 30% of patients
Flat or sloping configuration
Histopathologic studies reveal atrophy of the stria vascularis with degeneration of hair cells and cochlear neurons

Question 18

What is the prognosis for norrie?

Answer 18

Poor with universal blindness
Progressive SNHL in about 30% of cases
Infantile psychosis that is progressive
During middle age, psychosis and hallucinations are common

Question 19

What is the differential diagnosis for norrie?

Answer 19

Cytomegalovirus (CMV) infection
Rubella
Usher syndrome (Hearing loss and blindness – not due to RP in Norrie)