1. Genetics and Otolaryngology Bobby Tajudeen

2. Vocab Genome – collection of all genes that an organism possesses Gene – basic unit of biological information that can be transferred from parent to offspring Three broad categories of genetic disease – Chromosomal – Monogenic – “dominant” and “recessive” – Complex – genetics unclear

3. Genetics AD AS

4. X-Linked Mitochondrial

5. Most common type of genetic hearing loss is transmitted in what fashion? a.AR b.AD c.X-linked d.Mitochondrial

6. What is the structure?

7. A patient with Pendreds is most likely to to benefit from: a.Synthroid b.Thyroidectomy c.Amplification d.Steroid Burst

8. Pendred Syndrome Most common form of hereditary syndromic SNHL Autosomal recessive Affected individuals also have goiter Congenital severe-profound HL, bilateral Mutation in SLC26A4 gene Pendrin anion transporter involved in chloride and iodine transport Goiter in 2 nd decade, usually euthyroid Perchlorate discharge test Radiographs always show temporal bone anomaly either dilated vestibular aqueducts or Mondini dysplasia

9. A patient with hearing loss is diagnosed with Jervell-Lange Nielsen syndrome. Why did his brother die at a young age? a.Neurologic disease b.Cardiac disease c.Renal disease d.Thyroid disease

10. Jervell and Lange-Nielsen Syndrome Autosomal recessive Characterized by congenital deafness, prolonged Q-T, syncopal attacks KVLQT1 and KCNE1 genes important for potassium channels expressed in heart and inner ear Congenital, bilateral, severe to profound SNHL Prolonged QT can leads to ventricuar arrhythmias, syncopal attacks, and death Beta blockers reduce mortality from 71% to 6%

11. Two brothers developed congenital deaf- blindness with vestibular dysfunction. Which type of Ushers syndrome do they most likely have? a.Type 1 b.Type 2 c.Type 3 d.Type 4

12. Usher syndromes Autosomal recessive SNHL, retinitis pigmentosa, and often vestibular dysfunction Cause of 50% of deaf-blindness Three variants: – Type 1 – severe to profound congenital HL, vestibular dysfunction, retinitis pigmentosa develops in childhood – Type 2 – mod to severe HL, no vestibular dysfunction, retinal degeneration in 3 rd -4 th decade – Type 3 – progressive hearing loss, variable vestibular dysfunction, variable onset of retinitis pigmentosa

13. Which form of Waardenburg syndrome is not associated with dystopia canthorum? a.Type 1 b.Type 2 c.Type 3 d.Type 4

14. Which form of Waardenburg syndrome is associated with Hirschsprung disease? a.Type 1 b.Type 2 c.Type 3 d.Type 4

15. Waardenburg syndrome Autosomal dominant (except type 4) SNHL, pigmentary abnormalities (heterochromic iridis, white forelock, patchy skin depigmentation), craniofacial abnormalities (dystopia canthorum, synophrys, broad nasal root) Four types – Type 1 – presence of dystopia canthorum – Type 2 – no dystopia canthorum – Type 3 – skeletal abnormalities – Type 4 – associated with Hirschsprung disease

16. Gene Therapy Largely experimental at this point Involves replacing defective genes with functional variants, enhancing the expression of key genes, or suppressing genes Current goals are for the treatment of head and neck cancer, facilitate regrowth of hair cells in otology, and tissue engineering in plastics