1. Inner Ear Disorders- Children Lecture 15

2. Selected Causes of SNHL Genetic – Hereditary (congenital or late onset) Syndromic Non Syndromic Non – genetic – (congenital or late onset) Trauma  Prematurity  Anoxia Exposures/Infections  Rh Factor  Viral Infections (CMV)  Rubella

4. Embryology of the Inner Ear 3 rd week – inner ear starts to develop 6 th -10 th week – cochlear turns begin to develop 10 th -12 th week – organ of corti forms 25 th week – fully developed cochlea reaches adult size

5. How do genes work Genes: road map for synthesis of proteins Chromosomes – comprised of genes humans @30-40,000 23 pairs of chromosomes 22 pairs of autosomes 1 pair of sex chromosomes

6. Hereditary Patterns One chromosome from each parent is inherited Male XY - Female XX Gene: basic physical and functional unit of heredity comprised of DNA act as instructions to make proteins DNA is made up of 4 chemical letters.

7. Coding for DNA (Deoxyribonucleic acid) Code is read in groups of 3 letters Each code means a specific amino acid T- thymine A - adenine C – cytosine G – guanine TTA, CCG, TAT, CAT etc

8. Patterns of genetic codes Wildtype – common code/typical pattern Mutation - triplet codes can be changed by substitution deletion insertion Outcomes: beneficial (rare) neutral (common) deleterious (rare)

9. Pre-natal Causes of HL: Autosomal Dominant: one gene required from parent for HL to be inherited Autosomal Recessive: both parents are carriers for HL, but have normal hearing X-linked: recessive alleles are carried on the X chromosome, so HL occurs more in males than females Mitochondrial : gene passed from mother

10. Autosomal Dominant Mutations occur on an autosome (1-22) Child needs to inherit one copy of dominant trait to have disorder. 50% chance of an affected parent passing gene onto children Sometimes appears to “skip” generations

12. Autosomal Recessive Error occurs on autosome (Chr #1-22) Have to inherit a mutated gene from each parent. Most common pattern of transmission Up to 80% of profound genetic HL Half are associated with syndromes 25% chance that the offspring will be affected and manifest HL

14. X-linked Recessive: Recessive gene is carried on X chromosome Trait for HL is expressed in the presence of a single X chromosome Occurs more in males because they have single X males have a single x chromosome females have 2 copies of the x chromosome even if they inherit the defective gene, the other x chromosome will compensate. Sons have 50% chance of inheriting the trait and then the disorder Daughters have a 50% chance of inheriting the trait and being a carrier

16. Mitochondrial Mitochondria: powerhouse of the cell – also contain DNA Sperm have no mitochondria Only Mitochondria from mother’s egg passed on Only mothers can pass this on

17. Syndromic vs Non-syndromic HL NON-SYNDROMIC: Cases of hereditary HL & no associated abnormalities SYNDROMIC: Hereditary HL also assoc w/ other abnormalities i.e. external ear, skull, facial deformities, cleft palate, optic disorders, changes in eye, hair and skin pigmentation, thyroid disease, disorders of the heart, musculoskeletal anomalies, mental retardation, difficulty with balance

18. CHARGE Syndrome C= Coloboma of the eye H= Heart defects A= Atresia of nasopharynx R= retardation of growth or development G= Genital and/or unrinary problems E = Ear abnormalities and deafness Etiology: AD CHL – Common SNHL – 90% malformed cochlea

19. Waardenburg’s Syndrome Major Systems: intugement, ocular, craniofacial, gastrointenstinal, CNS Etiology: AD Quick clues: white forelock, wide set eyes, bi- color eyes, Hearing Disorders: 25% congenital, bilateral SNHL, mild to severe.

20. Usher Syndrome (Retinitis Pigmentosa) Major Systems: Auditory, vestibular, ocular, CNS Etiology: AR Quick clues: No external physical clues Association between HL and visual impairment, clumsy gait Hearing Disorders: Profound, bilateral SNHL Speech Disorders: Associated with HL

21. Usher Syndrome Type I: Profound SNHL, early onset, poor vestibular function Type II: Severe SNHL, good vestibular function, late onset Type III : Progressive, variable expression and onset

22. Treacher Collins Major Systems: Craniofacial, respiratory Etiology: AD Quick Clues: Slanting eyes, small jaw, malformed ears, Hearing Disorders: CHL, mild to moderate Feeding: sometimes cleft palate, small jaw effects breathing and feeding issues S/L – crowding in oral cavity, normal IQ, expressive/receptive delays assoc w hearing loss

24. Jervelle Lange Nielsen Major Systems: Cardiovascular, auditory Etiology: AR Quick clues: electrocardiographic abnormalities, fainting attacks, sudden cardiac death Hearing Disorders: Profound, congenital SNHL Flow of K+ ions disrupted in IE and cardiac muscle

25. Genetic:Late onset SNHL in children (Non-syndromic) Connexin 26 protein found on GJB2 gene Nonsyndromic, genetic cause of late onset HL Most common (50% of Recessive genetic HL ) Mutation on GJB2 protein Screening tests are available Connexin 30 Non-syndromic cause of late onset HL Less common

26. Genetic Cause of Late onset SNHL (Syndromic) Pendred’s (AR) Hypothyroidism HL Balance (ELVA)

27. Enlarged Vestibular Aqueduct Syndrome Genetic origin Usually a later onset SNHL Vestibular aqueduct – last IE structure to develop fully Sudden or fluctuating SNHL, progressive Aggravated by additional trauma to head Dxd with a CT scan and history

28. Non – genetic causes Childhood HL

29. Prematurity 5% of children born before 32 weeks present with HL by age of 5 Auditory system not fully developed if premature VLBW Aminoglycosides NIHL Oxygen supply

30. Prenatal causes of HL: Rh Factor Most people are Rh+ If mother is Rh- and partner is Rh+ Protein in “Rh” blood molecule is absent (negative) in the mother, but present (positive) in the fetus. When Rh negative blood is exposed to Rh positive blood, the Rh negative person begins producing antibodies to fight off invading blood An Rh- mother will develop antibodies to protect herself against the harmful effects of Rh + blood cells of the fetus. Her antibodies destroy the Rh + blood cells of the fetus which can no longer carry oxygen to the cochlea

31. Rh incompatibility Tx Early delivery Rhogam shots Gives temporary immunity for subsequent pregnancies

32. Cytomegalovirus (CMV) si-to-MEG- uh-lo-vi-rus Viral Infection – herpes group Transmission prenatally, perinatally or postnatally CMV spreads from person to person by direct contact. CMV infection is usually harmless, it can cause severe disease in persons with weakened immune systems Considered major cause of unknown etiology for SNHL Asymptomatic or Symptomatic CMV 31% of infants infected with CMV manifest HL (Johnson et al, 1986)

33. Who is at risk for CMV? Babies born to women who have a first-time CMV infection during pregnancy Pregnant women who work with infants and children Persons with weakened immune systems, including cancer patients on chemotherapy, organ transplant recipients, and persons with HIV infection

34. Non- genetic Anoxia: Oxygen deprivation Damages cells in the cochlea Rubella: viral infection vaccine since 1969 greatest impact if mother contracted during 1 st trimester

35. Meningitis Infection of the fluid around the spinal cord Causes inflammation of the meninges Viral – more common Bacterial – rare Outcome Viral: less severe Bacterial: 1/10 – fatal 1/7 severe handicap

36. Meningitis Bacteria and viruses that infect the skin, urinary system, gastrointestinal or respiratory tract can spread through the bloodstream to the meninges Spread by direct contact with the discharges from the nose or throat of an infected person Not easily spread – not airborne 10-25% of population is a carrier at any one time Bacteria do not live outside the body

37. Possible outcomes from bacterial meningitis SNHL Paralysis MR Seizures Coma/Death

38. Symptoms High fever Headache Stiff neck Nausea, vomiting, inactive Seizures in advanced stages Diagnosis: Spinal tap “Acute congestion of the stomach and brain”