Genetic Syndromes

Carol Rousseau, M.A., CCC-A Rochester Hearing and Speech Center Rochester, New York 15 October 2004

Genetic Syndromes  Syndrome is a pattern of abnormalities and/or symptoms that result from the same cause.

 More than 400 hereditary syndromes that involve hearing loss have been identified.

 Different syndromes are associated with various types and degrees of hearing loss.

Genetic Syndromes (Cont)  Congenital vs. delayed onset and/or progressive.

 Other physical and/or cognitive abnormalities.

 Genetic locations.

Genetic Syndromes

 Four Categories of Inheritance: • Autosomal Dominant • Autosomal Recessive • X-linked • Chromosome Abnormality

Autosomal Dominant  Waardenburg’s Syndrome  Treacher-Collins Syndrome  Alpert Syndrome  Alport Syndrome (types I,V,VI)  Crouzon Syndrome  Osteogenesis Imperfecta  Stickler Syndrome

Autosomal Dominant (cont)  Brancbio-Oto-Renal Syndrome (BOR)  CHARGE  Clefting Syndrome  Klippel-Feil Syndrome  Marfan’s Syndrome  Alport’s Syndrome

Waardenburg’s Syndrome  2-5% of individuals with congenital hearing loss have this syndrome  Two types have been defined  Congenital  Sensorineural, however hearing ranges from normal to profound unitlateral or bilateral

Waardenburg’s Syndrome (Cont)  Other characteristics: • White forelock in hair or premature greying • • • • Prominent root of nose Different colored eyes Inner ear dysplasia Usually normal intelligence

Waardenburg’s Syndrome -- Type I  Almost total deafness with some residual hearing in the low frequencies  Always includes lateral displacement of the inner corner of the eye  2q

Waardenburg’s Syndrome -- Type II  Moderate deafness with uniform hearing loss in the lower and middle frequencies but with improvement in the higher tones  Progressive hearing loss  3q

Waardenburg’s Syndrome -- Type III  A severe form, also called Klein Waardenburg  Partial albinism

Waardenburg’s Syndrome

Treacher Collins Syndrome  Congenital  Bilateral Conductive or mixed

Treacher Collins Syndrome (Cont)  Other characteristics: • Facial anomalies (depressed zygomatics, eyes slant downward laterally, receding mandible, mouth large and fish-like, dental anomalies, cleft palate).

• • Outer and middle ear deformities.

Typically normal intelligence, though mild mental retardation has been reported.

 5q

Treacher Collins Syndrome

Alpert Syndrome  Congenital  Mild to moderate Conductive Hearing Loss  Other characteristics: • Craniofacial anomalies affecting the ears (low set) • Stapes fixations • • • Fused fingers & toes Spina bifida Most have some degree of mental retardation

Alport Syndrome (Types I, V, VI)  Delayed onset; progressive  Sensorineural hearing loss  Other characteristics (varies by type): • Renal disease • • Ocular disorders Blood platelet defect  2q

Stickler Syndrome  Congenital or progressive  Conductive or Sensorineural  Other characteristics: • Cleft palate • • • • Myopia Renal detachment Often associated with Pierre Robin Sequence (30% of infants with Pierre Robin have Stickler) Normal intelligence 12q or 6p

Bronchio-Oto-Renal Syndrome (BOR)  Congenital or delayed onset  Sensorineural, Conductive, or Mixed (depending on area affected)  Other characteristics: • Outer, middle, and/or inner ear deformities • Brancial fistulas/cysts • • Renal disorders Normal intelligence  8q

CHARGE Association    Acronym for a group of anomalies that often appear together 85% have some degree of hearing loss (conductive, sensorineural, or mixed Stands for: • • • • • • Coloboma (defect of Iris, retina, or optic disc Heart disease (congenital) Atresia of the choanae (nasal passage) (Growth) Retardation Genital defects Ear anomolies

Crouzon Syndrome  Congenital  Conductive or Mixed Hearing loss  Other characteristics: • Prematurely fused cranial suture • • • • Protrusion of eyes and beak-shaped nose Variable outer/middle ear anomalies Normal intelligence Incidence with increased paternal age  10q

Kippel-Feil Sequence  Congenital  Sensorineural and/or conductive hearing loss  Other characteristics: • Fused cervical vertebrae • Paralysis of VIth cranial nerve • • • Short Neck Decreased head mobility Ossicle abnormalities

Oseogenesis Imperfecta  Progressive  Sensorineural, conductive and/or mixed hearing loss  Other characteristics: • Fragile Bones • Large Skull • • Hemorrhage tendency Stapes fixation  17q or 5p

Autosomal Recessive  Usher Syndrome  Goldenhar Syndrome  Hurler Syndrome  Pendred’s Syndrome  Alstrom Syndrome

Autosomal Recessive (Cont)  Frederick’s Ataxia  Fanconi Syndrome  Jervelland Lange-Nielsen Syndrome  Mobius’ Suyndrome

Usher Syndrome  Most common cause of profound hereditary deafness among children  Main cause of deaf-blindness  Congenital  Sensorineural  Three types

Usher I  Born with a complete, Profound hearing loss at all frequencies  Retinitis pigmentosa begins in early teens  Vestibular Dysfunction  Motor delays  Ia -- 14q  Ib & Ic -- 11q

Usher II  Born with moderate hearing loss in the low frequencies sloping to severe hearing loss in the high frequencies  Hearing loss progresses slightly over time  Progressive Retinitis pigmentosa • Occurs later in life and less severe than type 1  Usually no vestibular problems  Iia -- 1q

Usher III  Rarest form of the disorder  Born with normal hearing and vision, and they progressively lose both senses  Mild hearing loss develops in early 20s and becomes progressively worse  Vision loss starts in young adulthood and becomes progressively worse  Most cases documented in Finland

Goldenhar Syndrome  Congenital  Unilateral of bilateral Conductive  Close relationship with Treacher Collins

Goldenhar Syndrome (Cont)  Other characteristics: • • • • • • • • • Facial asymmetry Unilateral Microtiaand atresia Preauricular tags Eye anomalies Oral defects Club foot Congenital heart disease Abnormal semicircular canals Mental retardation in 15% of cases

Goldenhar Syndrome (Cont)

Hurler Syndrome (Mucopolysaccaridosis I)  Progressive  Sensorineural, Conductive or Mixed  Skeletal deformities  Dwarfism  Coarse facial features  Corneal clouding  Cardiogvascular disorders  Mental retardation

Pendred Syndrome  May be autosomal dominant with incomplete penetrance and variable expression  Variable -- congenital or progressive  Sensorineural  Other characteristics: • Thyroid enlargement (goiter)

Alstrom Syndrome  Delayed onset; progressive  Sensorineural  Other characteristics: • Retinitis pigmentosa • • • Cataract Diabetes mellitus Obesity

Frederick’s Ataxia  Delayed onset; progressive  Sensorineural  Other characteristics: • Ataxia • • Nystagmus Optic atrophy

X-Linked Syndromes  Alport Syndrome (Types II, III, IV)  Hunter Syndrome

Alport Syndrome (Types II, III, IV)  Delayed onset; progressive  Sensorineural  Affects only males  Other characteristics (varies by type) • Renal disease • Ocular disorders •  Xq blood platelet defect

Hunter Syndrome  Similar to Hurler Syndrome, but may be less severe and affects only males  Progressive  Sensorineural, conductive, mixed

Hunter Syndrome (Cont)  Other characteristics: • Skeletal deformities • • • • Dwarfism Coarse facial features Cardiovascular disorders Mental retardation

Chromosomal Abnormalities  Down Syndrome (Trisomy 21)  Trisomy 13  Trisomy 18