Download Genetic Syndromes

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 (lowset)
• 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
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
• blood platelet defect
 Xq
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