Deafness

Syndromic Deafness
Signs and symptoms
Jolijn Verseput, MD, clinical geneticist in training

26-02-2024
Content
• Deafness and heritability
• Signs and symptoms
• Good to recognize
• Cases
Deafness in children
• 3 in 1000 children
• 60% genetic cause
• 40% non-genetic
• Ototoxic drugs
• Acoustic trauma
• Infection, e.g. CMV
Hereditary Deafness
Hereditary Deafness
30% syndromic
(Deafness + other
symptoms)
15-24% dominant
70% non-
syndromic 75-85% recessive
(Only deafness, sometimes with
vertigo)
1-2% X-
Chromosomal
Syndromic Deafness
• Treacher collins • Crouzon • Opitz • Achondroplasia
• Pierre Robin • Stickler • Goldenhar • NF
• CHARGE • Nager • Meunke • Prader-Wili
• BOR • Plummer-Vinson • Beckwidth • Noonan
• VCF • ROW Wiedemann • Waldenstrom
• Apert • Melkerson • Saethre chotzen • MPS
• Turner Rosenthal • Pfeiffer • …
• Down • Progeria • Pendred
• Alport • Wallenberg • Usher
• Arnold Chiari • Waardenburg • Cogan
Recognizing Syndromic Deafness
Recognizing: inheritance
• Family history: 3 generations
• Draw the pedigree!
• No family history does not rule out genetic cause (de novo)
• Ask for relevant characteristics in family members

• Broad spectrum
• E.g.: cleft lip/palate, eye abnormalities, kidney abnormalities, facial
characteristics
Inheritance?
1. Autosomal dominant
2. Autosomal recessive
3. X-chromosomal
Inheritance?
3. X-chromosomal
Inheritance?
3. X-chromosomal
Recognizing: physical examination
• The ear
• Size
• Position
• Shape
• Pits/Creases
• Ear tags
Recognizing: physical examination
• Head
• Hair
• Eyes
• Mouth/palate/chin
• (submucosal)
• Neck
Good to recognize
Hearing and development
Any questions so far?

1. Down syndrome
• 1 in 750 newborns
• Trisomy 21
• Dysmorfic features: brachycephaly, flat midface, external ear deformities, upslant of

the eyes, epicanthal folds, macroglossia, short fingers, single palmar crease
• Other symptoms: short, hypotonia, mental retardation, behavioural issues, heart

defects, leukemia, dementia
Down syndrome
• ENT:
• OSAS 31 – 45%
• Relative adenotonsillar hypertrophy
• Relative macroglossia
• Hypotonia
• Chronic reflux pharyngitis/ laryngitis
• Trachea/ laryngomalacia
• Many infections (otitis, URTI)
• Hearing loss
Otological problems
• Small external ear
• Narrow meatus acousticus externa
• Otitis (media and externa) and cholesteatoma
• Anomaly of auditory bones
• Congenital anomalies cochlea
CHARGE
• Autosomal dominant inheritance
• C Coloboma
• H Heart defect  Tetralogy of Fallot, aortic arch anomaly, ASD/VSD
• A Choanal atresie/anosmia  also cleft
• R Retarded growth and development
• G Genital anomalies  hypogonadotrofic hypogonadism
• E Ear anomalies
Otological problems
• External ear (95 – 100%)
• Asymmetric, low set, broad
• Middle ear
• Absence m. stapedius/ sinus tympani/ pyramidalis
(92%), aberrant cranial nerve course (40-90%),
hypoplasia stapes (50%) and incus (11%)
• Inner ear
• Hypoplasia semicircular canal (100%)
VCF
Velocardiofacial syndrome, Di George syndrome
• 22q11.2-deletion syndrome
• AD, de novo or inherited
• Dysmorfic features: long face,
straight nose bridge, external ear shape malformations,
palatal cleft, long, thin fingers, hypertelorism
• Phenotype very broad

• Features: upper respiratory tract malformations, hearing loss, hypernasal speech,
cleft, congenital heart malformation, mental retardation, immunodeficiency ,
hypocalcemia, feeding difficulties, speech problems, vascular malformations
Otological problems
• Ear anomalies:
• Abberant shape: microtia,
cupped ears, square helix
• Preauricular pits or tags
• Narrow auditory meati
• Hearing loss
• Sensorineural
• Conductive
Good to recognize
Hearing and organ abnormalities
Eyes: Usher syndrome
• Autosomal recessive inheritance
• Multiple known genes
• Type 1, type 2, type 3 (and type 4)
• Deafness
• Retinitis pigmentosa
• Vertigo (type 1 & 3)
Otological problems: congenital
• Type 1
• Severe-profound
• Sensorineural
• Hearing aids inadequate
• Type 2
• Mild-moderate low frequencies
• Severe-profound high frequencies
• Hearing aids often adequate
Retinitis pigmentosa
• Night blindness
• Tunnel vision
• Blurry vision
• Functionaly blind:
• 40% age 40-50
• 60% age 50-60
• 75% age 60-70
Subtypes
Type Hearing Vision Vertigo
Usher 1 Congenital R.P starts before Yes
deafness age 10
Usher 2 Congenital high R.P. starts between No
frequency deafness age 10-20
Usher 3 Progressive hearing Progressive R.P. Variable
loss
Kidney: BOR
• Branchiootorenal spectrum disorder
• Criteria:
Otological problems
• Hearing loss > 90%
• Type: mixed (52%), conductive (33%) en perceptive (29%)
• Severity: mild (27%), moderate (22%), severe (33%), very severe(16%)
• Non-progressive in 70%, progressive in 30%
• External ear and/or canal malformations(30%), preauriculaire pits/cysts (82%), pre-auricular
tags (13%)
Renal abnormalities
• Renal agenesis, hypoplasia, dysplasia
• Uretero-pelvic junction obstruction
• Calyceal cysts
• Hydronephrosis
• Vesicoureteral reflux
Kidney: Alport syndrome
• Collagen disorder
• 66% XLAS, 20% AD, 15% AR
• Renal failure: hematuria, proteinuria < 30 years

• Cochlear: high-frequency sensorineural hearing loss
• XLAS: Late childhood – early adolescence (boys)
• ARAS: juvenile
• ADAS: adulthood
• Ocular: anterior lenticonus
Connective tissue: Stickler
• Connective tissue disorder
• Autosomal dominant & recessive
• Eyes: myopia, retinal detachment

• Ears: hearing loss of high frequencies
• Midface: underdevelopment, cleft
• Joints: spondyloepifysial dysplasia, early artritis
Pigmentation: Waardenburg
• Congenital sensorineural hearing loss
• Pigmentation
• White forelock
• Iris pigmentation abnormality
• Skin hypopigmentations
• Telecanthus
Cases
Some examples of these syndromes
Any questions?
Case 1
• 5 year old boy
• Reason for referal: hearing loss • Would you consider

something genetic?
• Medical history:
• 2023: Retinal detachment • Questions about the
patient?
• 2021: Astma
• 2021: Pneumonia • Questions about the
• 2019: Feeding difficulties family?
Pedigree:
• Would you consider

Hearing loss, knee Hearing loss
replacement age 33 something genetic?
• Anything else you

would like to
do/see/test?
Examination
• Picture Audiogram
• Expected diagnosis?
Case 2
• 17 year old woman Audiogram
• Reason of visit: follow up hearing loss
• Regular patient
• ENT patient since age 1
• Hearing aids
Pedigree
• If genetic: what type of

inheritance?
• Would you suspect

something genetic?
During the consult
• Doctor, can I ask you something else?
• More clumsy in the dark

• Could glasses help with this?
• Genetic? What would you consider?

• Which type of Usher syndrome?
Case 3
• 4 year old girl
• Reason for referal: recurrent otitis media

and suspected hearing loss, speech delay
• Picture  dysmorphisms?
Medical history • Would you consider
something genetic?
• Born 39+1, vaginal birth, birth weight +0.5 SD
• Diagnosis?
• Congenital malformations: VSD
• Neonatal period: failure to thrive, feeding difficulties
• Motor development: sitting 14 months, walking 19 months
• Speech: 2 word sentences

Take home messages
• Suspect hereditary cause? Draw the pedigree!
• Keep the comorbidity in mind
• Take a good look at your patient
• Sources to check:
• OMIM.org
• Genereviews

Deafness

Uploaded by

Copyright:

Available Formats

Deafness

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Deafness

Uploaded by

Copyright:

Available Formats

Syndromic Deafness

Signs and symptoms

Jolijn Verseput, MD, clinical geneticist in training

• Signs and symptoms

• 60% genetic cause

• Draw the pedigree!

• Ask for relevant characteristics in family members

Any questions so far?

• Dysmorfic features: brachycephaly, flat midface, external ear deformities, upslant of

• Other symptoms: short, hypotonia, mental retardation, behavioural issues, heart

• Phenotype very broad

• Type 1, type 2, type 3 (and type 4)

• Uretero-pelvic junction obstruction

• Renal failure: hematuria, proteinuria < 30 years

• Eyes: myopia, retinal detachment

• Congenital sensorineural hearing loss

• Reason for referal: hearing loss • Would you consider

• Would you consider

• Anything else you

• Reason of visit: follow up hearing loss

• ENT patient since age 1

• If genetic: what type of

• Would you suspect

• More clumsy in the dark

• Genetic? What would you consider?

• Reason for referal: recurrent otitis media

• Congenital malformations: VSD

• Neonatal period: failure to thrive, feeding difficulties

• Motor development: sitting 14 months, walking 19 months

• Speech: 2 word sentences

• Keep the comorbidity in mind

• Take a good look at your patient

You might also like