syndromic HL and deafness Flashcards
epidemiology
study of population health/outcomes
-understanding incidence of syndromes, prevalence of existing cases and looking at new cases
-observing patterns
-long term view
ways to reduce birth defects
take folic acid every day, stay up to date with immunizations, get regular medical checkups, avoid tobacco and prevent insect bites
what are some causes of HL
genetic and environmental factors either alone or together
gene mapping
finding the exact location using the # arm region band sequence
-the street address
gene cloning
production of exact copies of a particular gene of DNA sequence using genetic engineering techniques
-producing a clone of the DNA sequence
syndromic loci
syndromic disorders show abnormalities in many areas
nonsyndromic loci
nonsyndromic disorders are not associated with another other symptoms or disorders
DFN
deafness neurosensory
DFNA
autosomal dominant deafness neurosensory
DFNB
autosomal recessive deafness neurosensory
DFNX
x linked recessive deafness neurosensory
DFNY
y linked deafness neurosensory
DFNM
modifier deafness neurosensory
AUNA
auditory neuropathy deafness neurosensory
OTSC
otosclerosis
modifier genes
genotype does not prefix phenotype because of the complexity of the genome
-contribution of genetic background to phenotypic diversity reflects the additive and interactive effects of multiple genes
inner ear homeostasis
looking at the ionic balance of perilymph and endolymph within the ear
-between ions and fluids
-a tight control on ion movement across the membrane is vital
what ions are involved
sodium, potassium and there is also the interplay of chloride and calcium
what causes disorders of ion homeostasis
disruption of the strial ion transport mechanism is the final pathway common to many of the disorders
what are the two disorders of ion homeostasis
endolymphatic hydrops and endolypmphatic xerosis
endolymphatic hydrops
increased potassium transport in the endolymph or an increase in endolymph
-example is meniere’s disease
endolypmphatic xerosis
decreased potassium transport in the endolymph or decreased endolymph production
-related to connexin
cytogenetics
studies the cell, primarily the chromosome, structures and functions
-looking at the number and structure
aneuploidy
whole chromosome
trisomy vs. monosomy
most are livable vs. often lethal
what monosomy is survivable?
monosomy of sex chromosomes
what trisomy is survivable?
13, 18, 21 and X
how do we classify syndromic genetic deafness and hearing loss?
chromosome disorder, external changes, eye disease, musculoskeletal disease, renal disease, cardiac system disease, neurologic system disease, endocrine disorders, metabolic disorders, integumanetary system disease
chromosomal vs. single gene
whole body vs. system
chromosome disorder
HL due to chromosomal disorders but there are multiple genes being affected meaning multiple systems are affected
-main characteristic is intellectual disability
trisomy 13 (patau syndrome)
extra chromosome 13
-if survives birth, usually a short life span
-intellectual disability, blindness (coloboma’s), cleft lip, heart defects and extra toes/fingers
audiologic findings with trisomy 13
rounding of external ear, low set ear, severe to profound SNHL
trisomy 18 (edward’s syndrome)
extra chromosome 18
-very short life span, majority will die within 1st year
-intellectual disability, seizures, small mouth with arched palate, small lower jaw, clenched hands and heart defects
audiologic findings of trisomy 18
malformed and low set pinna, abnormal ME/IE and signs of heavy HL or deafness but unable to determine
trisomy 21 (down syndrome)
extra chromosome 21
-one of the few trisomies that can be tolerated within development
-life span increasing due to advancements
-intellectual disability, IQ decrease with age, flattened facial features, large tongue, short limbs, poor muscle tone, heart disease
audiologic findings in trisomy 21
low set pinna, narrow ear canal, conductive HL is most common
how is down syndrome passed on
nondisjunction, robertsonian translocation and mosaicism (x-inactivation)
nondisjunction inheritance
a pair of 21 chromosomes fails to separate in either the egg or sperm and as the embryo develops the extra chromosome is replicated in every cell of the body
robertsonian translocation
the chromosome breaks at its centromere and the long arm fuses to form a single chromosome with a single centromere and the short arms will fuse together as well
-centromere breaks, long (q) arms fuse with a new centromere, short (p) arms join together and will be lost
mosaicism
the presence of two or more cell lines or populations that differ genetically in an individual or tissue but is derived from a single zygote
-what adds variation
-will have a pool of various cells with different numbers in each
what is a specific type of mosaicism
x-inactivation
x-inactivation
prevents females from having twice as many x chromosomes as males
-since females get two x’s, one at random will be turned off
-creates a mosaic since some are inactivated and other are turned on
ring chromosome
occurs when an abnormal chromosome forms a ring structure
-both arms have a piece broken off and these ‘dead’ ends attach to each other to form a ring
chimerism
the presence of two sets of DNA or organs that do not match the DNA of the rest of the organisms
-very rare
-tends to occur within the embryonic development phase when two non-identical embryos merge together instead of growing on their own
turner syndrome (45, X0)
lacking a chromosome, having an X but missing the other sex chromosome
-most often will be female phenotype
-short stature with webbed neck
-immature gonads, infertility
-droopy eyelids
-IQ slightly below normal
audiologic findings of turner syndrome
low set pinna, narrow ear canal, recurrent ear infections and OM reported, speech and language aspects need to be addressed
klinefelter’s syndrome (47, XXY)
having an extra chromosome, having an extra X
-occurs in male births due to having the Y
-tall/thin with long legs
-hypogonadism around puberty with extra breast tissue
-male gonads but they are not functional
-IQ in low to normal range
-behavioral and psychosocial problems
audiologic findings in klinefelter’s syndrome
SNHL, poor auditory discrimination and delayed speech development
syndromic conditions associated with external ear changes
treacher collins, branchio-oto-renal, oculo-auriculo-vertebral and CHARGE syndrome
treacher collins syndrome
1st and 2nd brachial arch syndrome
-AD inheritance with deletions or nonsense mutations
-treacle protein that helps with neural crest cells
-facial structure abnormalaities, cleft palate, coloboma of iris, fish like mouth, facial nerve anomalies
audiologic findings in treacher collins
malformed pinna, atresia (no ear canal), absent or malformed ossicles, absence of ME cavity, mild to moderate conductive HL
treatment approach for treacher collins
cleft palate repaur, BAHA, speech therapy and educational intervention
branchio-oto-renal (BOR) syndrome
AD inheritance of HL with a transcription factor that is involved within the inner ear and kidney cell development
-cysts on kidneys and facial anomalies
audiologic findings of BOR
mixed HL is most common, branchial cysts, malformation of pinna, EAC stenosis, ossicular deformities and mondini’s malformation
oculo-auriculo-vertebral (OAV) spectrum
unilateral malformation of craniofacual structures from the 1st and 2nd arches with sporadic inheritance
-the mildest of the combined 3 complex disorders
-asymmetrical facial abnormalities, cardiac anomalies, vertebral anomalies and deafness or blindness
audiologic findings with OAV
pinna anomalies, conductive HL
CHARGE syndrome
most cases are sporadic however could be AD
-coloboma, heart defects, atresia of nasal conchae, retarded growth or development, genital abnormalities, ear anomalies
audiologic findings of CHARGE
external ear anomalies, ossicular malformations with ET dysfunction, mondini, considered to be a deaf/blind syndrome
syndromic conditions associated with eye disease
usher syndrome and norrie syndrome
usher syndrome
affects the ears and eyes with 3 types and is the most common AR syndromic HL
-most mutations lead to the loss of hair cells in the inner ear and gradual loss of rods and cones within the retina
-intellectual disability and psychosis, retinitis pigmentosa
-HL can mild to severe progressive SNHL
type 1 usher’s
more severe
-congenital severe to profound SNHL
-abnormal vestibular functions/gait ataxia
-delayed motor milestones
type 2 usher’s
milder than 1
-congenital mild to severe SNHL
-normal vestibular function
type 3 usher’s
rare with a progressive aspect
-progressive SNHL with progressive vestibular dysfunction
-could be a potential founder effect
explain some other common syndrome’s that have RP and HL
hallgren syndrome - ataxia, pigmentary retinopathy and SNHL
cockayne syndrome - associated with dwarfism and motor disturbances
alstrum syndrome - associated diabetes mellitus
refsum syndrome - triad of RP, peripheral neuropathy and ataxia
norrie syndrome (oculo-acoustico-cerebral dysplasia)
eyes, ears and brain
-rare disorder with x-linked recessive inheritance and is believed to be a deletion
-onset within the 2nd decade
-retinal detachment, congenital progressive blindess NOT caused by RP, cataracts and CNS involvement
audiologic findings of norrie syndrome
progressive moderate to severe SNHL, flat or sloping, atrophy of stria vascularis with degenerations of hair cells
syndromic conditions associated with musculoskeletal diseases
crouzon, stickler, achondroplasia and oteogenesis imperfecta
crouzon syndrome
premature closure of cranial sutures with resulting contracted skill
-AD transmission with mutations in the protein that makes fibroblast growth factors which turns cells to bone
-cranial and facial deformities due to development of bone affecting the ossification
audiologic findings of crouzon
atresia of EAC, ossicular defomity, absent or narrow oval/round window, conductive HL is most common
sitckler syndrome
distinctive facial apperance, eye abnormalities, HL and joint problems
-AD due to collagen based issues
-premature degeneration of joint leading to abnormalities, flat midface and cleft palate, severe myopia
-3 differenty types all with different genes
audiologic findings of stickler syndrome
mixed or pregressive high frequency SNHL
achondroplasia
form of short limbed dwarfism
-AD inheritance in familial cases but can be sporadic
-average trunk with short arms and legs, frontal bossing, stubby hands, bowed legs, lordotic lumbar spine, decrease in reproductive fitness
genotype with achondroplasia
-homozygosity has been proven lethal
-heterozygosity with 1 bad gene shows the phenotype
audiologic findings with achondroplasia
high risk of ear infections with some conductive HL and otosclerosis is also reported
osteogenesis imperfecta
generalized connective tissue disorder characterized by bone fragility (breaking bones easily)
-AD inheritance with mutation in collagen genes
-bone fragility, blue sclera and cardiovascular problems
audiologic findings with oteogenesis imperfecta
conductive or mixed HL, begins in late teens and progresses to profound deafness, tinnitus and vertigo often present
syndromic conditions associated with renal disease
alport syndrome
alport syndrome
nephritis and SNHL
-x linked in most cases
-collage gene affected
-kidney inflammation, hematuria, albuminuria, hypertension can occur
-premature death due to hypertension due to the body needing to work harder to move fluid through
audiologic findings with alport syndrome
bilateral SNHL, progressive
what must be present for a diagnosis of alport syndrome
3 of the following :
-positive family history of hematuria with or without renal failure
-electron microscope evidence of renal disease on renal biopsy
-characteristic ophthalmologic signs
-high frequency SNHL progressive during childhood
syndromic conditions associated with neurologic system diseases
auditory neuropathy spectrum disorder (ANSD), charcot-marie-tooth disease, friedreich ataxia, hereditary sensory and autonomic neuropathy type 1 (HSAN1) and neurofibromatosis (NF)
ANSD
functional OHC but problems present with CN 8 and the synapses results in present OAE’s but absent ARTs or ABRs
-majority are bilateral but it can be unilateral
-can be due to environmental, nonsyndromic, syndromic and mitochondrial inheritance
how does ANSD impact speech
severe impairment on speech perception because of the disruption of CN 8 firing
-within noise is highly affected
-abnormal speech testing
audiologic findings of ANSD
-important to test OAE’s, reflexes and speech as the audiogram is useless
-no speech in noise
-trial for amplification
CI’s are the most successful intervention for ANSD patients
charcot-marie-tooth (CMT) disease
progressive neurodegenerative disease characterized by polyneuropathy
-variable transmission however a deletion or point mutation occurs
-motor and sensory nerves affected, absent limb reflexes, chronic degeneration of peripheral nerves, full onset by 30 years
-100% penetrance
audiologic findings with CMT disease
SNHL with onset in childhood or adulthood, slowly progressive and may be caused by neuropathy due to demyleination of CN 8
friedreich ataxia
inability to coordinate voluntary muscular movement
-AR inheritance and gene is mapped to a protein that is importance for mitochondrial function and caused by triple expansion
-incoordination, dysarthria, nystagmus, diminished tendon reflexes, impairment of position senses, scoliosis, enlarged cardiac muscles
what is sufficient for a diagnosis for friedreich ataxia
hypoactive knee and ankle reflex, progressive cerebellar dysfunction and preadolescent onset
audiologic findings for friedrich ataxia
CN 8 and 2 that cause HL and visual impairment
hereditary sensory and autonomic neuropathy, type 1 (HSAN1)
neurodegenerative disorder
-early onset dementia, sensory neuropathy (loss of myelinated fibers) and early death is often reported
neurofibromatosis (NF)
NF1 and NF2 (look at chart for the breakdown of symptoms for each)
-AD inheritance with high penetrance and variable expressivity
-cafe-au-lait spots, vascular tumors that increase with age, color tumors in eye, neurofibromas, progressive visual loss is common, emotional and communication disorders
management of NF-2
surgery of the 8th nerve which causes the patient to go deaf, tumors can recur and CI’s are not an options so they will use auditory brainstem implant instead as it bypasses the damaged nerve
syndromic conditions associated with cardiac system disease
JLNS
jervell lange nielsen syndrome
cardiac and hearing syndrome due to potassium channel genes being affected
-AR syndromic HL
-long QT interval on EKG, congenital deafness, sudden death, syncopal episodes
audiologic findings with JLNS
congenital deafness
-can refer with justification
syndromic conditions associated with endocrine disorders
pendred and DIDMOA syndrome
-EVA by association with pendred
pendred syndrome
AR inheritance which makes the variability rare
-thyroid issues, delayed onset, variable expressivity, EVA
audiologic findings for pendred syndrome
profound and progressive SNHL
-variable onset
-more sever in HF
-abnormality of bony labyrinth
-abnormally wide or absent vestibular structures
enlarged vestibular aqueduct (EVA)
the endolymphatic duct and sac grows too large, leading to the fluid being affected
-due to same gene as seen within pendred’s
-variable audiologic phenotypes
-children can pass NBHS even if they have this
-SNHL
DIDMOAD syndrome
diabetes insipidus, diabetes mellitus, optic atrophy, deafness (SNHL)
-AR inheritance
-rare condition when kidney;s cannot prevent exertion of water
audiologic findings in DIDMOAD
bilateral SNHL with slowly progressive HL
-onset in 2nd decade
syndromic conditions associated with metabolic disorders
mucopolysaccharidosis (MPS) and biotinidase deficiency
mucopolysaccharidosis (MPS)
group for lysosomal storage diseases caused by various enzyme deficincies that catalyze the breakdown of glycosaminoglycans
-AR except MPS2 which is x-linked
-progressive course
audiologic findings with MPS
conductive HL caused by recurrent UPT infections and serous otitis media
MPS 1H (hurler syndrome)
recognized during infancy when patients are unusually large (abnormal growth)
-coarse facial features, corneal clouding, skeletal deformities, recurrent otitis media and HL, intellectual disability, death by around 10 years old
MPS 2 (hunter syndrome)
mild to severe form
-x linked transmission
-severe form is more common with rapid intellectual deterioration, coarsening of features, death by 10-15 years of age
-mild form is less common and survival to adulthood is possible
biotinidase deficiency
AR disorder with a mutation in the biotinidase gene and is treatable with supplements of biotin
-seizures, hypertonia and ataxia, skin rash, deafness
audiologic findings with biotinidase deficiency
SNHL and visual impairment are permanent and not reversible
syndromic conditions associated with integumentary system disease
waardenburg syndrome
waardenburg syndrome
four subtypes with different genes
-most common AD syndromic HL and caused by hereditary deficit of neural crest cells
-white forelock, prematuring graying of hair
-WS1, WS2, WS3, WS4 (look at diagram for more information on each)
audiologic findings of waardenburg syndrome
bilateral or unilateral HL with variable levels of HL
-vestibular abnormalities are reported
-atrophic changes in spiral ganglion and 8th nerve
-degeneration of organ of corti
ranking of most common autosomal dominant associated HL disorders
- waardenburg syndrome
- BOR
ranking of most common autosomal recessive associated HL disorders
- usher
- pendred’s
- JLNS
what are some common characteristics of chromosome disorders
intellectual disability, heart disease/defect and palate/jaw issues
what is one commonality within audiologic fundings for chromosomal disorders
pinna abnormalities
what are the common branchial arch syndromes
treacher collins, BOR, OAV
what are some common characteristics with branchial arch syndromes
pinna malformations, conductive HL, facial anomalies to variable extents
