Syndromic HL Disorders Flashcards
Treacher Collin’s Syndrome (Mandibulofacial Dysostosis)
~40% cases are autosomal dominance
~60% cases are are mutations (majority from having an older father)
First arch syndrome (affecting neural crest cell migration)
Audiologic features:
- malformed pinna
- atresia
- abnormal or absent ossicles
- absent ME cavity
- mild to moderate conductive HL > 50% cases
Differential Dx: Oculo-Auriculo-Vertebral Spectrum (OAV) disorder
Branchio-Oto-Renal (BOR) Syndrome
Autosomal dominant
Affects structures that develop from the branchial arches, ear, and kidneys.
Audiologic features:
- conductive, SNHL, or mixed HL
- branchial cysts/fistulas
- malformation of pinna
- stenosis of EAC
- Ossicular deformation (commonly stapes)
- cochlear deformation including Mondini’s malformation (incomplete cochlear coiling)
- rarely, vestibular anomalies like reduce caloric response
- HL can be delayed onset, rarely progressive
Differential Dx:
Alport’s syndrome
Oculo-Auriculo-Vertebral Spectrum (OAV)
Multifactorial inheritance pattern (typically sporadic gene mutation)
malformation of craniofacial structures developing from 1st and 2nd branchial arches
Audiological features:
- preauricular tags
- microtia
- stenosis of EAC
- conductive hearing loss more common than SNHL
- facial nerve paralysis
Differential Dx:
Treacher Collins syndrome
CHARGE Association/Syndrome
Inheritance pattern is unknown, most likely sporadic mutation (multifactorial).
- Some are mutation or deletion with an AD transmission. (risk may be influenced by increase paternal age)
Visual, auditory, nasal, growth, genital and urinary systems affected
C: coloboma of eye, H: heart defects, A: atresia of nasal conchae, R: retarded growth, G: Genital abnormalities, E: ear anomalies/deafness
Audiologic features:
- external ear floppiness
- ossicular malformations
- ET dysfunction
- Mondini malformation
- hypoplastic semicircular canals with balance issues
- cranial nerve dysfunction including facial palsy
Usher Syndrome (USH)
Autosomal recessive (most common recessive syndromic hearing loss)
- Mutation in gene involved in hair cell development and rods and cones in retina
Audiological features:
- For type I, congenital severe-to-profound SNHL with vestibular abnormality and gait ataxia
- For type II, congenital mild-to-severe SNHL, normal vestibular function
- For type III, progressive SNHL and progressive vestibular dysfunction
Differential Dx:
Norrie syndrome and other disorders with both RP and SNHL (Hallgren syndrome, Cockayne syndrome, Alstrum syndrome, Refsum syndrome)
Norrie Syndrome (Oculoacousticocerebral Dysplasia)
X-linked recessive inheritance pattern
Visual, hearing, and cortex problems (dementia)
Audiologic features:
- progressive moderate to severe SNHL (appearing around age 10 for 30% of the time)
- Atrophy of the stria vascularis with degeneration of hair cells and cochlear neurons
Differential Dx:
CMV, Rubella, and Usher’s
Crouzon’s Syndrome (Craniofacial Dysostosis)
Autosomal dominant inheritance pattern
- spontaneous mutations are common (paternal origin)
Musculoskeletal Disorder -Premature closure of the cranial sutures (cranial skull/small skull) and maxilla hypoplasia
Audiological features:
- Atresia of the EAC with ossicular deformity
- Absent or narrowed oval and/or round window
- Conductive hearing loss is common but mixed hearing loss is also reported
- The vestibular system is normal
Stickler Syndrome
Autosomal dominant with varying expressivity (severity)
- commonly from nonsense mutation
Musculoskeletal Disorder - Affects the architecture of collagen-based tissues (joint issues, severe myopia)
Audiological features:
- Associated with a mixed or progressive high frequency SNHL
- Hearing loss is reported in ~60% of Stickler type 1 patients and ~90% of type 2 patients
Achondroplasia
> 80% cases are sporadic mutation (multifactorial) with familial cases being autosomal dominant.
Musculoskeletal Disorder -Affects the size of the limbs
- homozygosity of dominant gene is lethal
Audiological features:
- >90% report history of ear infections with >70% report CHL
- Otosclerosis is also reported
Osteogenesis Imperfecta
Autosomal dominant inheritance
Musculoskeletal Disorders - Mutation in the collagen gene (generalized connective tissue disorder)
Audiological features:
- Conductive or mixed hearing loss in ~50% of families
- Hearing loss begins in late teens and progresses gradually to profound deafness
- Tinnitus and vertigo by the end of 4th and 5th decade
Alport Syndrome
Variable transmission - Commonly X-linked, ~15% autosomal recessive and rarely autosomal dominant
Renal disorder causing nephritis and SNHL
Audiological features:
- Bilateral variable progressive, initially high-frequency SNHL beginning about the first or second decade of life
- Normal vestibular function (except in some cases of the AD form)
Differential Dx:
Branchio-oto-renal syndrome
Auditory Neuropathy Spectrum Disorder (ANSD) or Auditory Synaptopathy
Mitochondrial inheritance pattern
For syndromic ANSD, often associated with peripheral neuropathies such as Charcot-Marie-Tooth and Friedreich’s Ataxia
Audiological features:
- OHCs are in tact, issues with CN VIII
- abnormal ABRs and ARTs
- Severe speech perception impairment
- commonly bilateral hearing loss, only 20% had unilateral (NICU babies)
- 60% had other cognitive disabilities (NICU babies)
Charcot-Marie-Tooth Disease
Variable transmission - Can be autosomal dominant, autosomal recessive, or X-linked recessive transmission
Progressive neurodegenerative disease characterized by polyneuropathy
Audiological features:
- SNHL with onset either in childhood or adulthood
- Hearing loss is slowly progressive
- Hearing loss may be cause by auditory neuropathy due to demyelination of CN VIII
Friedreich’s Ataxia
Autosomal recessive inheritance pattern - commonly caused by triplet expansion of the GAA trinucleotide repeat expansion
Neurodegenerative disorder that causes ataxia and other motor and reflex abnormalities
Audiological features:
- abnormalities in motor and sensory nerve conduction, including CN VIII and CN II, causing issues with hearing loss and visual impairment
- Nystagmus
- Progressive cerebellar dysfunction
Hereditary Sensory and Autonomic Neuropathy, Type 1 (HSAN1)
Autosomal dominant inheritance pattern
Neurodegenerative disorder characterized by early onset dementia and sensory neuropathy causing loss of feeling and ulcers
Audiological features:
- Adult onset of progressive SNHL progressing to deafness
Neurofibromatosis (NF)
Autosomal dominant inheritance pattern - high penetrance and variable expressivity (severity)
NF-1: peripheral - cafe-au-lait spots, cutaneous and subcutaneous fibromatous tumors, Lisch nodules of the eyes
Audiological features:
- 5% demonstrate CN VIII tumors
Differential Dx:
NF-2
NF-2: central - less common than NF-1. ~43% of cases will have >6 cafe-au-lait spots, intercranial tumors.
Audiological features:
- over 95% present with bilateral acoustic neuromas
- Auditory Brainstem Implant (ABI) for management
Differential Dx:
NF-1
Vestibular schwannoma
Jervell and Lange-Nielson Syndrome (JLNS)
Autosomal recessive inheritance pattern
Cardiac defects causing syncope and sudden death
Audiological features:
- congenital deafness
- bilateral severe-to-profound SNHL
- Complete degeneration of organ of corti
- Loss of sensory hair cells
Differential Dx:
Ward-Romano syndrome
Pendred Syndrome
Autosomal recessive inheritance pattern
Endocrine disorder - (thyroid issues) Disorder of chloride and iodine ion, affecting the iodine transport in thyroid and chloride ion transport in the cochlea
Audiologic features:
- SNHL, profound and rapidly progressing (variable onset and can be unilateral) more severe in HF
- abnormality of bony labyrinth (mondini malformation)
- abnormally wide or absent vestibular structures
- abnormal vestibular function (vertigo)
- enlarged vestibular aqueduct (EVA): when syndromic, is related to Pendred. Unilateral or bilateral moderate to profound, fluctuating and progressing, SNHL. Vestibular symptoms like vertigo may occur.
Differential Dx:
DFNB4 (SNHL, temporal bone abnormalities, EVA, NO thyroid defects)
DIDMOAD Syndrome or Wolfram Syndrome (WFS)
Autosomal recessive inheritance pattern
Endocrine disorder causing kidneys to not respond to ADH hormone and cannot prevent water excretion
Audiologic features:
- bilateral, SNHL
- slowly progressive
- onset is 2nd decade of life with atrophy of stria vascularis
- Reduced excitability of the vestibular system is reported
Mucopolysacchroidoses
Autosomal recessive EXCEPT for MPS II (Hunter syndrome) which is X-linked
Metabolic disorder - MPS I, II, II, IV, VI, VII, and IX
Audiologic features:
- Conductive HL from chronic respiratory tract infection and otitis media
- many have SNHL
- Combination of ME, cochlear, CN VIII and lower brainstem pathologies
MPS II - Hunter syndrome
X-linked inheritance pattern
MPS IIA more common and severe than MPS IIB
Prominent feature is abdominal hernia
MPS IH - Hurler syndrome
Autosomal recessive inheritance pattern
More severe form with most prominent feature being coarse facial features and macroglossia
Biotinidase Deficiency
Autosomal recessive inheritance pattern
Metabolic disorder - mainly a vitamin b complex deficiency where biotin is not released from proteins. Treatable with supplements
Audiologic features:
- deafness
Waardenburg Syndrome
Autosomal dominant inheritance pattern with variable expressivity
Integumentary disorder - caused by deficit of neural crest cells
Type I (WSI)
most common
Audiologic features:
- hearing loss (20% bilateral and 15% unilateral)
- moderate to profound HL
- vestibular abnormalities
- atrophic changes in the spiral ganglion and CN VIII
- degeneration of the organ of corti
- thickening of the basil membrane
Type II (WS2)
Same as type I except for dystopia canthorum
Type III (WS3)
Klein-Waardenburg syndrome
rare
Bilateral upper extremity defects in addition to WS1 findings
Type IV (WS4)
Shah-Waardenburg syndrome
rare
- deafness
