Genetics and Otolaryngology

Bobby Tajudeen

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

Genetics

AD

AS

X-Linked

Mitochondrial

• Most common type of genetic hearing loss is transmitted in what fashion?a. ARb. ADc. X-linkedd. Mitochondrial

What is the structure?

• A patient with Pendreds is most likely to to benefit from:a. Synthroidb. Thyroidectomyc. Amplificationd. Steroid Burst

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 2nd decade, usually euthyroid• Perchlorate discharge test• Radiographs always show temporal bone anomaly either

dilated vestibular aqueducts or Mondini dysplasia

• A patient with hearing loss is diagnosed with Jervell-Lange Nielsen syndrome. Why did his brother die at a young age?a. Neurologic diseaseb. Cardiac diseasec. Renal diseased. Thyroid disease

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%

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

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 3rd-4th decade

– Type 3 – progressive hearing loss, variable vestibular dysfunction, variable onset of retinitis pigmentosa

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

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

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

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