Genetics & Hearing Loss Flashcards
1
Q
Genetics and Hearing Loss
A
- Many HL (esp those in childhood) have genetic causes
- Often HL is only part of the phenotype
- Other family members, future siblings may be affected
2
Q
Etiologies of early hearing loss
A
(Figure 3-5)
3
Q
Hallmarks of autosomal dominance inheritance
A
- 1 parent expresses trait which they transmit to 50% of the offspring
- D/O typically HETEROzygous
4
Q
Hallmarks of recessive inheritance (Hint: 4)
A
- Parents are clinically normal and are carriers
- Can transmit to 25% of offspring per pregnancy
- 50% of offspring are carriers, 25% are genetically normal
- HOMOzygous
5
Q
Hallmarks of X-linked inheritance (Hint: 3)
A
- Carried on X chromosome and is recessive
- Females need both copies of deviant gene and males need only 1 copy to display phenotype
- Female carriers pass trait on to 50% of daughters who are themselves carriers and to 50% of sons who display the trait
6
Q
Hallmarks of mitochondrial inheritance (Hint: 4)
A
- Mitochondria are part of each cell that provides energy
- Have own genes made up of DNA
- DNA is inherited from mother
- Mitochondrial defects:
- can be recessive or dominant inherited
- can result in (non)syndromic HL
7
Q
Non-syndromic hearing loss Connexin 26/30 hearing loss (Hint: 6)
A
- Connexin 26 protein (controls iron transport; endoplymph; potassium)
- Import. to maintain endolymph equilibrium & high concentration of potassium
- GJB2 mutations are most common cause of non-synd HL
- HL ranges Mild - Profound
- Recessive deafness
- 2 mutations of GJB2 : may result in progressive HL
8
Q
Non-syndromic hearing loss
mitochondrial hearing loss (Hint: 8)
A
- Assoc. w/ neuromuscular HL
- HL may develop after antibiotic treatment
- Occasionally, HL associated w/ diabetes
- can be tied to mitochondrial mutation - HL: highly variable – flat, sloping or high freq type, progressive, or remain stable
- HL can begin in childhood > adulthood.
- Mother’s fault
- Recessive or dominate
- result in syndromic or nonsyndromic HL
9
Q
Non-syndromic hearing loss auditory neuropathy (Hint: 3)
A
1. Mult. etiologies
o Environ. or genetic
2. Syndromic or Non
3. Typically prelingual
- mod to profound
10
Q
Phenotypes of:
Branchio-oto-renal Syndrome (BOR) (Hint: 3)
A
- Conductive, sensorineural, or mixed
- can be progressive and range in severity - Ear pits in about 80% of BOR patients
- abnormal kidneys
11
Q
Charge Association
A
C = coloboma (defect of the eye) o bilat or unilat o may affect iris, retina, or disc o degree of visual impair. varies H = heart defects A = atresia of choanae (opening of the nasal cavity into the nasopharynx) R = retarded growth & development G = genital hypoplasia E = ear anomalies o abnormalities of the pinnae o HL may be conductive or sensorineural
12
Q
Apert syndrome (Hint: 6)
A
- Mental retardation
- Ocular hypertelorism
- Flat facial profile
- Syndactyly of hands or feet (fusion of the hands and fusion of the feet)
- Typically conductive HL
- Autosomal dominant (but can be sporadic)
13
Q
Stickler syndrome (Hint: 8)
A
- Midfacial flattening
- Long, thin extremities
- Cleft palate
- Bony enlargement of ankles, knees, joints during first few years of life
- Joints may be very loose
- Arthritis can worsen in older age
- Progressive myopia
- May have retinal detachment
- May cause increased pressure (glaucoma)
- Low percentage of sensorineural or mixed HL
- Mild to severe, can be progressive
- Autosomal dominant
- Mild midfacial hypoplasia
14
Q
Treacher Collins syndrome (Hint: 9)
A
- Downward sloping palpebral fissures (distance between eyelid → eyelids slant downward and might not have lwr eyelids)
- Depressed cheekbones
- Deformed pinnae & receding chin
- Coloboma (absence) of 5. Often will have cleft or incomplete soft palate
- Often have a conductive or mixed loss
- Congen. bilat conductive HL is most common
- Malformations of ossicles or labyrinth
- Autosomal dominant (or sporadic new mutation)
15
Q
Genetic HL w/ Associated Eye Disease: Usher syndrome (Hint: 9)
A
- Retinitis pigmentosa (RP) & sensorineural HL (SNHL)
- RP: degeneration of photoreceptor cells in the retina
- Types of Usher Synd:
- Type I (most severe): Congenital profound SNHL, balance problems, RP
- Type II: Congenital moderate-to-severe SNHL, RP, no balance problems
- Type III: Progressive SNHL (late onset), RP, and possible balance problems
- RP causes gradual loss of vision - night blindness and tunnel vision
- Total blindness by age 50 in about 40% of the population
- 90% have severe SNHL; 10% moderate hearing loss
- Some mental retardation and psychosis
- Autosomal recessive condition
- In pop. that intermarry (i.e., Cajun)
16
Q
Genetic HL w/ Integumentary System Disease: Waardenberg syndrome (Hint: 9)
A
- Widely spaced medial canthi (space between the eyes is wider than usual)
- Flat nasal root
- Confluent eyebrows (unibrow)
- White forelock (a lock of hair growing just above the forehead)
- Patchy areas of pigmentation
- Heterochromia → 2 diff colored eyes
- Approx. 50% with SNHL, often severe to profound
- Autosomal dominant transmission
- Schools for the deaf, but no severe ID
17
Q
Genetic HL w/ Renal Disease: Alport syndrome (Hint: 5)
A
- Many diff degrees of prog. SNHL
- males > females
- Small dysfunctional kidneys
- Progressive nephritis (inflammation of kidney) with uremia (more blood in urine)
- X-linked inheritance usually
18
Q
Genetic HL w/ Metabolic and Other Abnormalities:
Neurofibromatosis Type 2 (Hint: 8)
A
- Vestibular schwannomas AKA acoustic neuromas (tumor on vestibular portion of schwann cells on CN VIII 2. sensory-neural hearing loss
- Tumors may be unilateral or bilateral
- HL = prog.
- CI isn’t going to work
- Sometimes receive auditory brainstem implant
- Need mult. MRI to monitor tumor because it can grow back
- Profound neural deafness results post-surgery for tumors
19
Q
Genetic HL w/ Associated Chromosomal Disorders: Down syndrome (Hint: 10)
A
- Middle ear problems
- Small anomalous pinna/auricles/ossicles
- Upslanting papebral fissures (corners of eyes)
- Epicanthal folds (eyelids slant upwards)
- Flat facial profile
- Cardiac malformations
- Intel dis or dev delay
- Conductive HL
- High incidence of middle ear effusion
- Impacted cerumen
20
Q
Define: genetic counseling
A
The examination of an individual’s chromosomes, genes, proteins and/or other analytes for alterations associated with genetic disorders or conditions
21
Q
Genetic counseling and 9 types of testing
A
- Diagnostic testing
- Carrier testing
- Prenatal testing
- Preimplantation genetic diagnosis
- Genetic profiling of embryos prior to implantation (as a form of embryo profiling)
- Presymptomatic genetic testing
- Pharmacogenetic genetic testing
- Paternity testing
- Forensic DNA analysis or DNA fingerprinting
22
Q
Limitations of genetic counseling (Hint: 3)
A
- Medical genetic tests are specific for particular D/O and can’t ID D/O not directly tested.
- May not always be able to:
- predict age of onset
- severity of D/P
- determine best course of treatment
- If negative, medical genetic tests may offer limited info
23
Q
Risks of Genetic Testing (Hint: 6)
A
- The physical risks typically small, esp if test only requires blood/urine sample or cheek swab.
- Risks higher if tissue samples/biopsies are required (how it is acquired & amount)
- In the case of prenatal testing - small risk of miscarriage:
- chorionic villus sampling (CVS)
- amniocentesis
- fetal blood sampling
- No risk of miscarriage:
- fetal ultrasonography
- Soc/emo consequences & feelings of:
- anger
- guilt
- anxiety
- depression.
- Financial consequences, loss of insurance/job
24
Q
Names of genes
A
nonsyndromic will be DFN (a) dominant or (b) recessive, and a # for order that genes were mapped
