Syndromic Hearing Loss and Deafness Flashcards
1
Q
look at slide 7
A
2
Q
What percentage of Hl is due to genetics
A
50%
3
Q
What percent of HL is environmental/ non-genetic ?
A
25%
4
Q
what percentage of HL is due to idiopathic ?
A
25%
5
Q
what category does non-syndromic and syndromic belong to?
A
genetic
6
Q
What percentage of HL does non syndromic contribute to ?
A
70%
7
Q
What percentage of HL does syndromic contribute to ?
A
30%
8
Q
what percent does autosomal recessive contribute to in HL?
A
75-80%
9
Q
What percentage of autosomal dominant contributes to HL?
A
15-24%
10
Q
what percentage of HL is due to x linked ?
A
1-2%
11
Q
What percentage of HL is due to mitochondrial effect?
A
less than 1%
12
Q
What is gene mapping?
A
exact location of a gene on a chromosome
like a street address of the gene on the chromosome
13
Q
What is gene cloning
A
The production of exact copies (clones) of a particular gene or DNA sequence using genetic engineering techniques
14
Q
what is syndromic loci?
A
Syndromic disorders show abnormalities in many area
15
Q
what are nonsyndromic conditions
A
Nonsyndromic disorders are not associated with other S/S
16
Q
how can modifier genes affect genes
A
Modifier genes can affect the phenotypic outcome of a given genotype by interacting in the same as the disease gene
17
Q
Does the genotype affect the phenotype ?
A
The genotype does not necessarily predict phenotype because of the complexity of the genome
The contribution of genetic background to phenotypic diversity reflects the additive and interactive effects of multiple genes
18
Q
what is the source of phenotypic variation?
A
Often, individual genes do not act alone but rather in combination with many other genes, therefore, modifier genes are a common source of phenotypic variation in human populations
19
Q
modifier genes can?
A
These modifier genes can modulate expressivity (severity), penetrance, age of onset, progression of a disease, or pleiotropy (two or more seemingly unrelated phenotypic traits) in individuals with Mendelian traits
20
Q
what is homeostasis ?
A
It is the ability of an organism or a cell to maintain internal equilibrium by adjusting its physiological processes
21
Q
what is inner ear homeostasis?
A
“The process by which chemical equilibrium of inner ear fluids and tissues is maintained”
22
Q
what is needed for proper inner ear function?
A
For proper inner ear function, a tight control on the ion movement across the cell membranes is necessary
These functions include
Hair cell functions
Regulation of extracellular endolymph and perilymph
Conduction of nerve impulses
23
Q
What are major ions involved with inner ear homeostasis ?
A
Sodium (NA+)
Potassium (K+)
24
Q
what other ions are involved with the role of inner homeostasis?
A
Chloride (Cl-)
Calcium (CA2+)
25
what are ion homeostasis controlled by?
-ION CHANNELS AND AND TRANSPORTERS IN THE PLASMA MEMBRANE
Ion homeostasis is controlled by numerous ion channels and transporters in the plasma membrane of cells, especially cells lining the scala media
26
Many disorders of cochlear hearing loss and vestibular dysfunction are caused by ?
disruption of ion homeostasis
27
what does the disruption of the strial ion transport cause IN RELATION TO HEARING LOSS?
-PERMENANTHEARING LOSS
-Genetic disorders associated with ion transport and pathways are often associated with permanent hearing loss
-Disorders from other causes are often transient and may recover without treatment
28
the majority of non-syndromic HL is due to ?
alteration of proteins that prevent movement of K+ from the organ of corti to the lateral wall and into the stria
29
hearing loss can result from ?
(in terms of potassium)
-increased or decreased activity of the strial process
-Increased K+ transport in the endolymph or increased endolymph production
-endolymphatic hydrops
-an example: Meniere disease is an increase
-Decreased K+ transport in the endolymph or decreased endolymph production
-endolymphatic Xerosis
30
Endolymphatic xerosis caused by?
various genetic anomalies is believed to be the cause of hearing loss in humans
-its an example of permanent disorders of ion homeostasis
31
what are an example of endolymphatic xerosis?
1)Connexin 26 related hearing loss
2)KCNE1 and KCNQ1
32
what is connexin 26?
instructions for making a protein called gap junction beta 2
-Gene mutation results in abnormal connexin gap junction proteins
-Responsible by itself for 50 to 80% of all AR hearing loss
33
what is KCNE1 and KCNQ1?
-These genes produce proteins that make up K+ channels on the apical stria
-Their absence leads to reduced endolymph and associated hearing loss seen in Jervell-Lange-Nielsen syndrome
34
What are classification of genetic deafness and hearing loss
-Chromosome disorders
-External ear changes
-treacher collins syndrome, branchio-oto-renal syndrome (BOR)
-Eye disease
-ushers sydrome, norrie syndrome
-Musculoskeletal disease
-crouzon sydrome, stickler syndrome
-Renal disease
-alports syndrome
-Cardiac system disease
-jerrell-lange-nielsen
-Neurologic/Neuromuscular system disease
-friedreich atraxia
-Endocrine disorders
- pendred syndrome
-Metablolic disorders
- bioindase deficiency, muccopolysacharidose (MPS)
-Integumentary system disease
-waardenburg syndrome
-No associated physical or mental characteristics
-connexin hearing loss and deafness
35
Are all the classifications listed above syndromic or non-syndromic ?
syndromic
36
what are other commonly used classification system classifies hearing loss?
1)Congenital genetic group
-present at birth
2)Delayed onset genetic group
-early onset
-childhood
-late onset
-adulthood
-something like cancer or Alzheimer's, you can have it but it will show up later in life
3)Congenital non-genetic group
-born with it but doesn't come from parents
4)Delayed onset non-genetic group
-early onset
-childhood
-ex meningitis
-late onset:
-adulthood
-an example is trauma, presbycusis
37
what is cytogenetics?
-functionof the chromosomes
-were talking about chromosomes
-Cytogenetics is a branch of genetics that studies structure and function of the cell, especially the chromosomes
-Too many or too few chromosomes/genes can have lethal consequences to a developing organism
38
why are patients with chromosome defects not address HL as a priority ?
-Patients with chromosome defects, especially trisomies, often are so severely compromised, both physically and mentally, that hearing status is not adequately addressed
-they have other issues going on that's why
-For proper clinical management, assessment of hearing can be crucial
-Individuals faced with physical and mental hurdles may have their intellectual development further compromised by the burden of an undiagnosed hearing loss
39
what is more tolerable, monosomy or trisomies ?
-extra chromosome material is tolerated better than chromosome loss
-Monosomy of any autosome is lethal
-except sex chromosomes, they can still live
40
What 3 autosomal trisomies and sex trisomy can survuve full term
-13, 18, 21, X
THESE ARE THE ONLY ONES SURVIVABLE
-ALL THE OTHER FATAL
41
what has documented the increasing risk factor of chromosome trisomy
advance maternal age pregnancy, and a small amount of advance paternal age
42
what disorder is tied with trisomy 13?
Patau Syndrome
43
what type of disorder is patau syndrome?
chromosomal disorder
44
which trisomy has the most several birth defects in patau syndrome?
trisomy 13
only 5-10% of live births survive past one year
45
what are some symptoms seen in patau syndrome?
-cleft lip
-intellectual disabilites
-missing corpus callosum
-blindness
-Severe intellectual disability due to various brain defects
-forebrain defects
- agenesis (complete or partial absence of the corpus callosum
-microcephaly
-Bilateral iris, retinal, and optic nerve colobomas resulting in blindness
-A coloboma is missing pieces of tissue in structures that form the eye
-Cleft lip/palate
-Hand and feet polydactyly (supernumerary fingers and toes)
-Heart defects such as ventriculo-septal defect
46
what are audiological findings we see in patau syndrome
Audiologic findings
Abnormal helices
Low-set ear
Most children show a severe to profound bilateral sensioroineural hearing loss or deafness
Temporal bone studies show
Abnormalities of the cochlea and vestibular system
Hearing is often not evaluated because of low survival rate and significant/possible life threatening, medical, neurological, cognitive impairments
47
What is trisomy 18 called?
edwards syndrome
48
who is most likely seen to have edwards syndrome? and whats they birth rate?
-WOMEN
1 in 5000 births; Marked female (3:1) preponderance, possibly due to higher miscarriage of male fetus
50% die within first week; 90% during 1st year
49
what are some symptoms of edwards syndrome?
-Profound intellectual disability with seizures
-Small mouth with high arched palate
Clenched hands with overlapping fingers
-Heart defects, which are often the cause of death
50
what are audiologic findings seen in edwards syndrome?
low set pinna,
no ossification of ossicles and retarded cochleadevelopment
-Malformed and low-set pinnae
=Temporal bone studies; abnormal middle/inner ear, including failed ossification of ossicles and retarded cochlear development
-Based on temporal bone studies, most probably severely HI or deaf; audiometric analysis not reported
51
what is the most common chromosome defect in humans?
Trisomy 21- down syndrome
52
what is one of the fewest trisomies to be tolerated during development and why
-21, down syndrome, is the smallest somatic chromosome with the fewest number of genes, therefore, one of the few trisomies that can be tolerated during development
-even then only 30% of fetuses survive the term
53
what are clinical features in down syndrome ?
Clinical features include :
-intelectualdisabilites, short limbs, flattened facial features and epilepsy
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-
-
-
-
-
-
- - intellectual disability and developmental delays; most common cause of intellectual disability
-IQ decreases with age
-General IQ for a 2-year-old is 60 while IQ maybe 35 for a 10-year-old
-50% of adults with DS display an Alzheimer Disease-like phenotype beginning at ~ 40 years with similar brain pathology (their brain is similar to a brain with someone with alzheimers)
-Flattened facial features with furrowed & large tongue (macroglossia)
-Short limbs
-Short broad hands with transverse palmar crease
-Hypotonia in infancy
Upslanted palpebral fissures
-Palpebral fissure is the anatomic name for the separation between the upper and lower eyelids
-Epilepsy is common
Males nearly always infertile; females have reduced fertility
-Congenital heart disease is common
-40% affected w/ a potentially life threatening heart defect
54
audiologic findings in down sydrome
-lowset pinna
-conductive, SNHL, or mixed
-narrow ear canals, with middle and inner ear defects
-Low-set pinnae
-Stenotic ,narrow, external ear canals, with middle and inner ear defects
-Hearing loss in 60% of cases secondary to serous otitis media and impacted cerumen in stenotic ear canals
-Hearing loss can be conductive, SNHL, or mixed
55
what is robertsonian translocation
itswhen 2 acrocentric chromosomes fuse together
In ~ 4% of cases of Down’s syndrome, the extra 21 is a result of Robertsonian translocation
-an arocentric chromosome feature (13,14,15,21,22,Y)
56
what occurs at the chromosome level during robertsonian translocation
-During a Robertsonian translocation, the participating chromosomes break at their centromeres and the long arms fuse to form a single chromosome with a single centromere
-The short arms also join to form a reciprocal product, which typically contains nonessential genes and is usually lost within a few cell divisions
57
what happens when the large arm of chromosome 21 joins robertsonian translocation ?
when a Robertsonian translocation joins the long arm of chromosome 21 with the long arm of chromosome 14 (or 15), the heterozygous carrier is phenotypically normal or balanced
58
how does robertsonian translocation translate and cause down syndrome
Translocation Down syndrome is a type of Down syndrome that is caused when a chromosome 21 becomes attached to another chromosome. In this case, there are three 21 chromosomes, but one of the 21 chromosomes is attached to another chromosome.
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- - the progeny of this carrier may inherit an unbalanced (abnormal phenotype) trisomy 21, causing Down Syndrome
-If mother is RT carrier, risk of 2nd trisomy 21 pregnancy = 10 to 15%
-If father is RT carrier the risk is < 2%
59
what else can happen in unbalanced forms of robertsonian translocation?
In unbalanced forms, Robertsonian translocations also can result in other syndromes of multiple malformations including trisomy 13 (Patau syndrome)
60
look at slide 40
61
what percentage of mosaicism can cause downsyndrome ?
~ 1% of Down’s syndrome cases are caused by mosaicism
62
what is mosaicism?
when a person has two or more genetically different sets of cells in his or her body.
Presence of two or more cell lines (cell populations) that differ genetically in an individual or tissue but that are derived from a single zygote
63
can mosaicism happen in somatic cells or germ cells?
Mosaicism in single genes can be either somatic or germ cells
64
how can mosaicism help define the weird stuff we see in clinic ?
-it helps explain the number of unusual cases we see in clinic
-for ex ,
when parents have a normal phenotype but the child comes out with a rare autosomal dominant condition
the occurrence of rare autosomal dominant condition in an offspring whose parents are phenotypically normal such as achondroplasia (dwarfism), hemophilia (blood condition) and some blood conditions
65
what are other conditions in mosaicism?
mosaic Klinefelter syndrome and mosaic turner syndrome
66
what is x inactivation?
-X-inactivation or Lyonization is a form of germ cell mosaicism
- it's when the X gene is inactive
67
who is consider mosaic between the 2 genders?
WOMEN ARE MOSAICS !!
68
what is the purpose of x inactivation?
X-inactivation prevents females from having twice as many X chromosome gene products as males
69
what x chromose is chosen to be inactive ?
it's random
70
what will happen once the x linked is inactive ?
once an X chromosome is inactivated it will remain inactive throughout the lifetime of the cell and its descendants in the organism
71
the genetic variation of down syndrome summary
-An extra copy of chromosome 21 can be inherited in three ways
1)Trisomy 21 (Nondisjunction) (~ 95% of cases)
-Prior to or at conception, a pair of 21chromosomes in either the sperm or the egg fails to separate (nondisjunction)
-As the embryo develops, the extra chromosome is replicated in every cell of the body and accounts for an extra chromosome 21
2)Translocation (~ 4% of cases)
-Part of chromosome 21 breaks off during cell division and attaches to another chromosome, typically chromosome 14
-The total number of chromosomes in the cells remain 46 but the presence of an extra part of chromosome 21 causes the phenotype of Down syndrome
3)Mosaicism (~ 1% of cases)
-Occurs when nondisjunction of chromosome 21 takes place in one but not all of the initial cell divisions after fertilization
-When this occurs, there is a mixture of two types of cells, some containing the usual 46 chromosomes and others containing 47, which contain an extra chromosome 21
-Individuals with mosaic Down syndrome may have fewer characteristics of Down syndrome but it is difficult to broadly generalize due to the variability of this condition
72
what are ring chromosome ?
Ring chromosome is a rare genetic condition caused by having an abnormal chromosome that forms a ring
73
how do chromosomes look like in people with ring chromosome?
-In people with ring chromosome, one chromosome is usually intact but the other forms a ring
-When a ring forms, both arms of a chromosome break and the broken ‘sticky’ ends fuse at the breakage points
-The broken fragments are lost, and with them any genes they may contain
74
where can ring chromosome occur ?
Ring chromosome can occur in any chromosome but are more common in acrocentric chromosome
75
what rings chromosomes might be affected ?
r. 13, r.14, r.15, r.21, r.22, r.Y
76
are ring chromosomes sporadic or inherited?
sporadic but when it's inherited it comes from mom
77
Ring chromosome affect what in cells?
cell growth
78
how does ring chromosomes disrupt cell growth ?
ring chromosome formation may disrupt this process because the ring chromosome during cell division may not behave properly and may be entangled, broken, and could double in size
79
what might result from ring chromosomes ?
-As a result cells may arise with the wrong amount of chromosome material (too much or too little), which is called mosaicism
-Most commonly, these individuals also have cells with 46 normal chromosomes, which generally softens the impact of the ring
80
what is chimerism?
Chimerism may manifest as the presence of two sets of DNA, or organs that do not match the DNA of the rest of the organism
-and happens in early embryonic development
81
how does chimerism happen
two non-identical twin embryos merging together instead of growing on their own
82
what are some characteristics seen in Chimerism?
-Hermaphroditic characteristics, having both male and female sex organs, can be a sign of chimerism
-Can be seen in cases of bone marrow transplant
83
what is turner syndrome?
it looks like 45, X0
One of the x chromosomes is gone in the females XX chromosome, typically being pregnant with a baby will not cause this
84
Which X in turner syndrome is gone?
typically dad's X is gone
85
what are clinical factors seen in turners syndrome
Short stature with thick or webbed neck
Wide chest with broadly spaced nipples and streak gonads
-patients are typically infertile
IQ may be slightly below normal
Turner is a condition where an X-linked recessive trait may express phenotypically in females because only one X chromosome is present
86
what are audiologic findings in turners syndrome?
-Low-set, protruding pinna and narrow ear canals
-Recurrent ear infections and chronic OM reported in over 50% of cases
-reoccurring otitis media and have long term speech and language defects
87
what is Klinefelter's syndrome?
they have an extra X chromosome
it looks like (47, XXXY)
88
what are clinical features seen in Klinefelter's syndrome?
-Tall and thin with disproportionately long legs
-Development relatively normal till puberty when hypogonadism is more evident with gynecomastia
-IQ in the low-normal range
-Behavioral and psychosocial problems; poor attention & judgment
89
audiologic features seen in klinefelter's syndrome ?
SNHL reported in ~ 20% of cases with poor auditory discrimination and delayed speech development
90
turners and klinefelter's syndrome are similar in what manner ?
Both Turner and Klinefelter’s syndrome are generally spontaneous mutations and not inherited
91
is treachers collins sydrome dominant or recessive ?
~ 40% cases autosomal dominant (AD) with variable expressivity and almost 100% penetrance
92
what are risk factors treachers collins syndrome
fathers tending to being older
93
what are some clinical symptoms seen in treacher collins syndrome
abnormalities of facial structures formed from the first pharyngeal arch; First arch syndrome
1) receding arch
2) lower eyelids/ absent eyelashes
3)fish like mouth because of deficiency of muscles of the upper lip and small lower jaw
4) facial nerve abnormalities (part of the 2nd brachial arch)
5) can have normal intelligence, mild intellectual disability
94
audiological findings in treacher collins
-malformed pinna and external canal atresia
-absent or malformed ossicles, especially the stapes
-complete absense of the ME cavity that could be filled with connective tissue
-mild to moderate bilateral conductive HL
-SNHL is rarely reported
95
what are some treatments for treacher collins
-Requires multidisciplinary approach
-Cleft palate repaired at 9 to 12 months of age
-Hearing loss treated by bone conduction amplification or BAHA
-Speech therapy and educational intervention
96
what is a differential diagnosis for treacher collins
oculo-auriculo- veterbral spectrum (OAV) disorder
97
what does branchio-oto-renal (BOR) syndrome affect?
Affects structures developing from branchial arches, ears, & kidneys
98
what is the second most syndrome of AD HL
Branchio-Oto-Renal (BOR) Syndrome
99
what are some clinical features seen in Branchio-Oto-Renal (BOR) Syndrome?
-Renal anomalies (65% to 80%) including large, polycystic kidneys
-Facial nerve anomalies reported in < 5% of individuals but rarely leads to facial paralysis
100
what are some audiologic findings in branchio-oto-renal (BOR) syndrome?
-Conductive, SNHL, or mixed hearing loss (90%)
-Persistent branchial cysts/fistulas (60%), commonly present in lower 1/3 of the neck
-Malformation of pinna (35%)
-External auditory canal stenosis (30%)
-Ossicular deformities including stapes fixation
-Deformities of the inner ear including -
Mondini’s malformation
-Vestibular anomalies rare and include reduced caloric response
101
what type of hearing loss can be seen in branchio-oto-renal syndrome?
all 3 different types of HL can be seen in members of the same family
-HL can be delayed onset, but it's rarely progressive
102
can branchio-oto-renal syndrome affect pregnancy? if yes then how?
-Oligohydramnios (Also called Potter’s syndrome)
-It means too little amniotic fluid, which can affect the development of the fetus
-After about four months of pregnancy, the kidneys of a normal fetus will produce amniotic fluid
-If the fetus has kidney abnormalities, the amount of amniotic fluid may be too low
-Fetal genetic conditions that can cause oligohydramnios are:
-autosomal dominant: polycystic kidney disease (BOR)
-autosomal recessive: polycystic kidney disease
103
summary of characteristics findings in BOR are
-Autosomal dominant transmission with variable expressivity
-Renal abnormalities of varying severity
-polycistic, large ugly kidneys
-Unilateral or bilateral preauricular pits
-External ear anomalies
-Unilateral or bilateral branchial fistulas
-Hearing loss that can be
-SNHL, conductive or mixed
104
are oculo-auriculo-vertebral spectrum sporadic gene mutations ?
yes
104
what is a differential diagnosis for branchio-oto-renal syndrome
alports syndrome
104
are chromosomes normal in oculo-auriculo-vertebral spectrum normal ?
yes
105
where does oculo-auriculo-vertebral develop from?
the 1st and 2nd branchial arches
106
what are some clinical feature seen in oculo-auriculo-vertebral spectrum
-Facial asymmetry is the predominant presentation
-Unilateral facial and mandibular hypoplasia, and cleft palate common
-Even with bilateral involvement, one side of face more severely affected
-Nearly all cranial nerves involved including VII N resulting in facial weakness or paralysis
-Congenital cardiac anomalies are common
-Vertebral anomalies include scoliosis, spina bifida, and rib anomalies
-Mental retardation is uncommon
-The life span is normal
-Deafness/blindness in one or both ears/eyes can occur
-Internal organ(s) can either be unilaterally absent or underdeveloped
107
what are some audiological findings in oculo-auriculo-vertebral spectrum
-Pinna anomalies including preauricular tags, microtia, stenosis of EAC
-Conductive hearing loss more common but rarely SNHL can occur
108
what is a differential diagnosis for oculo-auriculo-vertebral spectrum?
treacher collins syndrome
it differentiates in this one is unilateral and treachers is bilateral
109
what does C.H.A.R.G.E association/syndrome stand for
-Coloboma of the eye
-Heart defects
-Atresia of nasal choanae
-Retarded of growth and/or -development
-Genital and/or urinary abnormalities (hyogonadism)
-Ear anomalies and/or deafness (typically SNHL and progressive)
-External ear anomalies (maybe too floppy to support HAs)
-Ossicular malformations with almost universal ET dysfunction
-Mondini anomaly
-Hypoplastic semicircular canals with balance issues
-Considered a deaf/blind syndrome although complete deafness or blindness is uncommon
110
What is the most common AUTOSOMAL RECESSIVE syndrome in HL?
Ushers syndrom
111
what is the prevalence among profoundly deaf children for ushers?
3-8% of deaf people have ushers
112
what is the prevalence of ushers in deaf and blind?
50%
113
what is the heredity for ushers?
-Autosomal recessive; consanguinity often reported
-Multiple genes and multiple chromosomes involved
1)One Ush type I gene mapped to chromosome 11p14
2)One Ush type II gene mapped to chromosome 1q
3)One USH type III gene mapped to 3q21-25
114
ifa mutation occurs, what is going to be affected in ushers syndrome?
-the development and maintainence of the HC along with the structure and funtion of the rods and cones
-These genes have instructions for making proteins (e.g., myosin) that play important roles in the development and maintenance of hair cells
-In the retina, these genes are involved in determining the structure and function of rods and cones
-Most mutations responsible for Usher syndrome lead to loss of hair cells in the inner ear and gradual loss of rods and cones in retina
115
what symptoms are seen in ushers?
-Intellectual disability and psychosis
-Hearing loss can be mild to severe progressive SNHL
-The most common symptoms are progressive hearing loss and blindness associated with retinitis pigmentosa (RP), which typically develops during the 2nd decade
-progressive loss of vision
116
what is retinitis pigmentosa and where is it seen?
-it's seen in ushers
-It is the scarring of the retinal pigment layer with uneven gathering of pigment into clusters
-Regions initially affected are at the periphery of the retina and then progresses towards the macula or center
117
how many types of ushers are there?
3
118
what does type 1 usher's look like
-Congenital severe-to-profound SNHL
Traditional amplification is ineffective
- -Abnormal vestibular function and gait ataxia
-Delayed motor milestones
-hearing aids dont work
119
what does ty[e 2 ushers look like ?
-Congenital mild-to-severe SNHL
-HAs are effective
-Normal vestibular function
120
what does type 3 ushers look like?
Type III (rare)
Progressive SNHL with progressive vestibular dysfunction
In the U.S., types I and II are the most common
121
what is a differential diagnosis for ushers syndrome?
morrie syndrome and disorders with retinitis pigmentosa and SNHL
122
what are other retinis pigmentosa and HL syndromes?
-hallgren syndrome
-cockayne syndrome (rare)
-alstrum syndrome
-refsum syndrome
123
what does hallgreens syndrom look like?
Generalized ataxia, pigmentary retinopathy, and SNHL
124
what does cockayne syndrome look like ?
Associated dwarfism and motor disturbances
125
what does alstrum sundrome look like?
-Associated diabetes mellitus
-Blindness sets in by ~ 20 years of age
126
what does refsum syndrome
-Triad of retinitis pigmentosa, peripheral polyneuropathy, and ataxia
-SNHL, which is often asymmetrical
-Defect in phytanic acid metabolism; treatable with dietary changes
127
what is the seen in norrie syndrome?
Visual problems, associated with SNHL and dementia
128
what is the heredity for norrie syndrome?
-x linked recessive inheritance
-boys will manifest the phenotype because the girls have the other good X to balance it out (so girls end up being carriers)
129
what is some clinical features seen in norrie syndrome
-Typical onset, is in the early 2nd decade
-Most common cause of congenital retinal detachment
-Congenital progressive blindness generally not caused by retinitis pigmentosa
-Cataracts and atrophy of iris visible to even the casual observer
-CNS involvement
-intellectual disability
-seizure
-psychiatric disorders reported but not for all cases
130
what are the audiologic findings in norrie syndrome ?
-Progressive moderate to severe SNHL developing at about ~ 10 years in ~ 30% of patients
-Flat or sloping configuration
-Histopathologic studies reveal atrophy of the stria vascularis w/ degeneration of hair cells and cochlear neurons
131
what is the prognosis of norrie syndrome?
-Poor with universal blindness
-Progressive SNHL in about 30% of cases
-Infantile psychosis that is progressive
-During middle age, psychosis and hallucinations are common
132
what is the differential diagnosis for norrie syndrome ?
1)cytomegavirus (CMV) infection:
-can cause neurological, psychological, hearing and vision problems and alot of them only have onlyv HL
2) Rubella
-german measles
3)Ushers syndrome (HL and blindness not because of retintitis pigmentosa but the CNS involvement is specific to norrie syndrome
133
what is the inheritance of crouzon's syndrome ?
-Autosomal dominant transmission
-Spontaneous mutations fairly common and of paternal origin
134
what is crouzon's syndrome ?
Dysostosis is a disorder of the development of bone, particularly affecting ossification
135
what are clinical features seen in crouzon's syndrome ?
-Early fusion of cranial bones causes
-Marked cranial and facial deformities
-Abnormal shape of the head and appearance of face
-A major problem is maxillary hypoplasia
-Bulging eyes/vision problems caused by shallow eye sockets
-Mild ocular hypertelorism (increased space b/w eyes), orbital proptosis
-Occasional cleft lip and palate
-mental status is normal
136
what are audiologic findings seen in crouzons syndrome ?
-atresia of EAC w/ ossicular deformity
- -you use a baha because they have no ear canal
-absent or narrowed oral and/or round window
-conductive HL is common but mixed HL also reported
-vestibular system is normal cause the hair cells are normal
137
what is the inheritance of sticklers syndrome
-Autosomal dominant with variable expressivity
-Collagen disorder affecting architecture of collagen-based tissues
-Virtually all mutations involve premature stop codons (nonsense mutations)
-reason why it happens is because it prematures stop codons
138
how many types of stickler are there
3
139
what are clinical features seen in sticklers syndrome ?
-Characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems
-~30% show premature degeneration of joints leading to skeletal/joint abnormalities beginning in the 3rd or 4th decade
-Flat mid face and occasionally cleft or high arched palate
-Severe myopia; cataracts and glaucoma can occur but blindness rare
140
what are some audiologic findings in sticklers ?
Associated with a mixed or progressive high frequency SNHL
Hearing loss is reported in 60% of patients with type 1 patients and 90% in patients with sticklers type 2
141
what is achrondroplasia ?
It is a form of short-limbed dwarfism
-torso is normal but the limbs are short
142
is achondroplasia dominant or recessive ?
AD inheritance is demonstrated
143
can achodroplasia be lethal ?
yes because both parents are giving it to the child, homozygosity plays a part
144
what are some mutation problems seen in achondroplasia ?
The mutation causes problems in converting cartilage to bone (ossification), particularly in the long bones of the arms and legs
145
what are some clinical findings in achondroplasia ?
-An average-size trunk with short arms and legs
-Enlarged head and frontal bossing
Short stubby hands
-Legs frequently bowed of because lax knee ligaments
-Intelligence is generally normal
-Lordotic lumbar spine with prominent buttocks
-Short and narrow pelvis
-Reproductive fitness reduced primarily because of social difficulties in finding a mate (how hard or easy it is to have children)
-achondroplasia women tend to have premature babies and problems during delivery because of the abnormal pelvis
146
what are some audiologic findings in achondroplasia ?
--90% have a history of ear infections with 70% of those being a conductive hL
-otosclerosis is also reported
147
is osteogenesis imperfecta dom or recessive?
Autosomal dominant inheritance
148
what are some clinical findings seen in osteogenesis imperfecta
Generalized connective tissue disorder characterized mainly by bone fragility
-Multiple bone fractures, usually resulting from minimal trauma (bones break easily)
-Fractures are rare in the neonatal period
-Fracture tendency is constant from childhood to puberty, then decreasing till menopause in women and 6th decade in men
-Blue sclerae
-Cardiovascular problems such as valvular insufficiency
-Conductive or mixed hearing loss in ~ 50% of families
-it starts in the late teens and progresses gradually to profound deafness
- tinnittis and vertigo by the end of theiy 40s and 50s
149
what is alports syndrome?
Nephritis (kidney issues) and sensorineural hearing loss
150
what is the heredity of alports ?
-Heterogeneous, with most cases X-linked dominant or recessive-85%
-AR - 15%
-AD -1 to 5%
151
what causes alports ?
Classic Alport syndrome is due to a defect in type IV collagen COL4 gene responsible for the formation of
-cells of spiral ligament, basilar membrane, stria vascularis,
-lens of the eyes
- glomerull of the kidneys
152
what are some clincal findings in alports
Characterized by progressive glomerulonephritis with intermittent hematuria (blood in urine) and SNHL
153
what are some audiologic findings in alport syndrome
bilateral variable progressive intitially high freq SNHL at the beginning of their life (10-20 year olds)
-normal vestibular function (except in some case of autosomal dominant forms)
154
what can be seen in kidney inflammation in alports syndrome?
-hematuria
-ALBUMINURIA (a protein, if it's in urine then it means you have poor kindey problems)
-and progressive kidney failure
-hypertension
155
what are eye findings in alports syndrome ?
-congenital cataracts and corneal erosion (eye problems)
-retinopathy
some have it an some don't
156
can people due of alports
yes in their 20s to 40s because of the hypertension and renal failure
157
what criteria must be met in order to be diagnosed with alports
you must meet 3 out of the 4 conditions
1)Positive family history of hematuria with or without renal failure
2)Electron microscope evidence of renal disease on renal biopsy
3)Characteristic opthalmologic signs
-In X-linked form
-Characteristic lens abnormalities and central retinopathy
-High frequency SNHL progressive during childhood
158
what is a differential diagnosis for alports
-brachial-oto-renal (bor)
-both have kidney issues, hemotinuralm and hl
they're different because bor affects the arches and alports doesnt
159
How is ANSD defined operationally?
-OAEs are normal but reflexes aren't
-senosry cells are intacts and fuctions ( IHC and OHC are normal) but the 8th nerve fibers and synapse are affected. They have even a harder time listening to noise
-Intact otoacoustic emissions (although sometimes they may disappear later in the condition)
-OAEs related to OHC function; OHCs intact in ANSD
-Or present cochlear microphonic (CM) with absent emissions
-CM also shows activity from OHCs through a different mechanism
-Grossly abnormal/absent ARTs, electrocochleography (ECochG), and ABR responses
160
what is something to important to remember in ANSD?
Severe impairment of speech perception especially in noise because of disruption of synchronous VIII N firing
161
is ansd genetic or environmental
it's both
162
how does ANDS look like in a nonsyndromic condition?
-Observed in families or
-No other family member may be affected
-Autosomal recessive mode of inheritance!!!!!!!!!!!!!!!!!!! BOLDDDDDD
-Abnormal gene copy inherited from each parent
163
how does ansd look like in a syndromic condition
Often associated with peripheral neuropathies
-ex charcot-marie-tooth syndrome and friedreich axia
164
how is the a mitochondrial mode of inheritance affect ANSD ?
the affected females will have affected offspring but the affected male wouldnt
165
what is the environmental cause in ANSD
-In the conditions described below, if the arterial supply is affected then OHCs will be affected and OAEs can be absent
-Infectious disorder due to viral involvement
-E.g., mumps and measles (can be unilateral)
-Immune disorders can be accompanied by deafness typical to ANSD (Rance & Starr, 2011)
For example, Guillian-Barre syndrome
-Affects proximal nerve roots and proximal portions of VIII N
-Deafness and paralysis with a lengthy period of recovery
166
do hearing aids work for ANSD
yes but it's limited. it works if there residual hearing
it could reduce the effects of noise, distance, and reverberation in a space
167
how can we manage education in ansd?
-auditory and visual stimulation
-Manual communication with cued speech or ASL
-Formal education method to facilitate literacy/self-dependence
168
what is the most successful form of treatment in ansd
CI
169
are audiograms helpful in ansd?
NO
because its based on the HC and ansd is not based on the hc so you cant make any judgements so you need to do reflexes cause their absent and oaes to see if they're present
170
what is charcot marie tooth disease
-One of the most common inherited neurological disorders
type 1A is the most common
171
how can charcot marie tooth be transmitted ?
Can be inherited as AD, AR, or X-linked recessive transmission
172
how is charcot marie tooth characterized ?
-It is a progressive neurodegenerative disease characterized by polyneuropathy (will get worse over time)
-it affects both motor and sensory nerves
-Absent limb reflexes
-Chronic degeneration of peripheral nerves causing muscular atrophy
-muscles are wasting soldemly seen abovethe elbows and mid thighs
Age of onset typically between 12 to 20 years
THERE IS NO ESCAPE OF GETTING THIS, IT'S 100% PENETRENCE
173
what are some audiologic findings in charcot marie tooth disease?
-SNHL with onset either in childhood or adulthood
-Hearing loss is slowly progressive
-Hearing loss maybe caused by auditory neuropathy due to demyelination of CN VIII
174
what is the most common form of autosomal recessive ATAXIA
friedreich ataxia
175
what is the heredity of friedreichs ataxia
Autosomal recessive neurodegenerative disorder
176
what are come characteristics of friedreich ataxia
-The disorder is usually manifest before adolescence
It is characterized by :
-Incoordination of limb movements
-Dysarthria
-Nystagmus
-Diminished or absent tendon reflexes and
-Babinski sign
-Impairment of position and vibratory senses
-Scoliosis, pes cavus (abnormally high foot arch), and hammertoe
-Cardiomyopathy
-Abnormalities in motor and sensory nerve conduction, including CN VIII and CN II, which cause hearing loss and visual impairment
177
what do you need to be diagnosised with friedreichs ataxia ?
-hyperactive knee and ankle reflex
-progressive cerebellar dysfunction
-preadolescent onset
178
is hereditary sensory and autonomic neuropathy type 1 dom or recessive
dom and a rare disorder
179
how is Hereditary Sensory and Autonomic Neuropathy, Type 1 characterized
-Adult-onset (~ 37 yrs.) of progressive
-SNHL progressing to deafness
-Early-onset dementia
-Sensory neuropathy by 20 to 35 years resulting in lack of feelings in toes and ulceration, in some cases requiring amputation
-Generally an early death by the 4th to 5th decade, is reported
180
is neurofibriomatosis dom or recessive
dom with high penetrance and variable expressivity (phenotype varies)
181
what are some characteristics in neurofibrosis type 1
Cafe-au-lait spots
-coffee spots
-Cutaneous & subcutaneous fibromatous tumors
-Highly vascular tumors that increase in number to as many as a thousand during a lifetime
-Usually appear around puberty
-Infiltrate surrounding tissue causing serious abnormalities and deformities
-Lisch nodules in the eye
-Pigmented hamartomatous (benign tumor) nodular aggregate of dendritic melanocytes in the iris found in 94% of NF1 cases
-About 5% demonstrate VIII N tumors
182
what is the percentage of incidence in neurofibrosis 2
50% genetic (AD) and 50% spontaneous mutation
100% (complete) penetrance
183
what can be seen in neurofibrosis 2
Characterized by a progressive disabling/disfiguring course
Less than half (~ 43%) demonstrate café au lait spots
-0% presents more than 6 spots
184
what are some symptoms seem in neurofibrosis 2
-Benign, multilobulated, non-encapsulated tumors
-Over 95% present with bilateral acoustic neuromas
-At a higher risk for other intracranial tumor such as meningioma, astrocytomas, ependymomas, and glioma
-Progressive visual loss is common
-Intelligence is not impaired
-Emotional consequences and devastating communication disorder
185
what diagnosis can we do for neurofibrosis ?
-Audiologic and vestibular assessment
-CT scans and MRI with contrast
186
what is a differential diagnosis for Neurofibrosis 2?
neurofibrosis 1
vestibular shwanomma
187
what is a give away that neurofibrosis is present?
there are multiple BILATERAL vestibular schwanoma
188
how can we manage neurofibrosis?
-Surgery, which necessitates destruction of the VIII nerve which renders patients deaf, often for both ears
-Even after surgery, these tumors can recur
-Cochlear implants are not an option as there is no nerve to electrically stimulate
-The only current management option is an auditory brainstem implant (ABI)
189
what is the heredity for Jervell and lange nielsen syndrome (JLNS)
-3rd most common RECESSIVE syndromic HL
-Consanguinity reported
-When the JLNS gene behaves in an AD fashion (compound heterozygous mutation), carrier parents also may die suddenly due to cardiac problems
190
what are the clinical features seen in JLNS ?
Long-QT interval (>500 ms) on the EKG with functional heart disease, congenital deafness, and sudden death
191
Why is the QT interval elongated in JLNS?
-Long QT caused by cardiac muscles that take longer than usual to recharge between beats
-Syncopal (fainting) episodes and/or sudden death
-In most cases, syncopal attacks are precipitated by fear, excitement, physical exertion, and loud noises
-Patients need to be under the care of a cardiologist and treated
-Congenital deafness
-Bilateral severe-to-profound SNHL
-Complete degeneration of organ of corti
-Loss of sensory hair cells
-Generally no vestibular symptoms reported
Seizures reported in some cases
192
What is sudden infant death syndrome supposedly related with?
JLNS but more info is needed to confirm
193
Should JLNS be genetically tested
YES BECAUSE THERE IS A CARDIAC CONCERN
194
how can we manage JLNS?
-eliminate fear and excitement
-Stress, exercise and drugs
-cardiac consult
195
What is a differential diagnosis for JLNS ?
Ward-Romano syndrome
196
What is the incidence of Pendred Syndrome?
-Second most common form of RECESSIVE syndromic deafness
-Accounts for about 5 to 8% of all individuals with profound hearing loss
-Phenotypic variability within families
197
What are some clinical features seen in pendreds ?
-The main feature is a thyroid goiter (80% of affected individuals)
-Delayed onset, typically not present at birth but may present by early puberty
-Hypothyroidism (low thyroid hormones) is reported in about 40% of affected individuals
198
What are audiologic findings ?
-SNHL (100%) that is usually profound and rapidly progressive
-Can be variable in onset and can be unilateral
-More severe in the higher frequencies
-Abnormality of bony labyrinth and radiographic malformations of the inner ear often associated with Mondini malformation (< 2.5 turns of the normal cochlea)
-Abnormally wide or absent vestibular structures
-Abnormal vestibular function in majority of cases including vertigo may be present
-Enlarged vestibular aqueduct (EVA) diagnosed on CT scan (85%)
199
what is a differential diagnosis for pendreds?
-DFNB4 is a mutation of the SLC26A4 pendrin gene characterized by
-Prelingual profound nonsyndromic SNHL and temporal bone abnormalities, typically EVA
-no thyroid enlargement
200
whar are some audiologic findings in an enlarged vestibular aquaduct?
-EVA is the most common anatomic abnormality contributing to permanent hearing loss in children
-EVA causes variable audiologic phenotypes, including
-Unilateral or bilateral SNHL hearing loss
-Moderate to profound, often with progression or fluctuation
-Vestibular symptoms like paroxysmal vertigo may also occur
201
do newborns with enlarge vestibular aqueducts hpass their new born hearing screenings ?
YES, they aren't typically diagnosed until 3-4 years old
202
how can patients reduce the likelihood of progressive HL in enlarged vestibular aqueduct?
-Should avoid contact sports that might lead to head injury
-Wear head protection when engaged in activities such as bicycle riding or skiing that might lead to head injury
-Avoid situations that can lead to barotrauma (extreme, rapid changes in air pressure), such as scuba diving or hyperbaric oxygen treatment
203
is there any treatment for enlarged vestibular aqueduct?
-No treatment has proven effective in reducing the hearing loss associated with EVA or in slowing its progression
204
what does DIDMOAD/ wolfram syndrome stand for ?
Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, SNHL (Deafness)
(has nothing to do with blood sugar
205
what is seen in DIDMOAD syndrome ?
-Diabetes insipidus (DI) is an uncommon condition in which the kidneys are unable to prevent the excretion of water
-DI is caused by either the kidneys not responding to the antidiuretic hormone (ADH) or lack of ADH produced by the hypothalamus
206
what are audiologic and vestibular findings in DIDMOAD/wolfram syndrome ?
-Bilateral, sensorineural, slowly progressive hearing loss (60-85%)
-Onset in 2nd decade of life with atrophy of the stria vascularis
-Reduced excitability of the vestibular system is reported
207
what is mucopolysacchroidoses ?
-lysosomal storage diseases caused by various enzyme deficiencies that catalyze the breakdown of glycosaminoglycans (mucopolysaccharides)
208
Mucopolysacchroidoses is recessive, dom, or x-linked ?
autosomal recessive except for MPS II (Hunter syndrome), which is X-linked
209
what are audiotry syndrome in mucopolysacchroidoses ?
-a conductive hearing loss caused by recurrent upper respiratory tract infection and serous otitis media
-Many patients also may demonstrate SNHL
-The auditory brainstem also has been described as abnormal in nonspecific ways
210
how can we audiologically manage mucopolysacchroidoses ?
-pe tubes
-hearing aids for both conductive and SNHL
211
what are early diagnosis seen in hurler syndrome?
-Coarse facial features
-Macroglossia (large tongue) and corneal clouding
-Characteristic skeletal deformities
-Dysostosis multiplex (skeletal abnormalities) & joint contractures
-Recurrent otitis media and hearing loss
-Intellectual disability
-Cardiac failure may occur prior to diagnosis
-Despite intervention, death by ~ 10 years
*IT'S SEEN AT EARLY AGE SO 16-18 MONTHS
212
on a scale of mild to severe, how does hurler syndrome rank?
its manifestation is seen severe
213
is hunter syndrome recessive or x linked ?
x linked
214
what are clinical features seen in hunters ?
-Rapid intellectual deterioration
-Progression of dysostosis multiplex
-Coarsening of features similar to Hurler’s syndrome
-Abdominal hernia with protruding abdomen & chronic diarrhea
-Death between 10 to 15 years of age
215
is biotinidase deficiency recessive, dom, x linked ?
recessive
216
what is biotinidase deficiency ?
-In this disorder, biotin is not released from proteins in the diet during digestion resulting in biotin deficiency
-Treatable & preventable with biotin supplements
217
what are some symptoms in biotinidase deficiency ?
-Seizures
Hypertonia and ataxia
-Developmental delay
-Skin rash
-Optic atrophy
-Deafness
-SNHL and visual impairments aren't reversible once they develop
218
why is early intervention important for biotinidase deficiency?
because all these symptoms can go away by supplements but this typically isn't diagnosed early
219
is waardenburg syndrome recessive, dom, x linked
-DOMINANT with variable expressivity
- caused by a deficit of neural crest cells
220
how many waardenburgs are there
4 types
221
what are audiologic and clinical findings in waardenbury type 1
-hearing loss
-lateral displacement of the inner angles of the eye
-unibrow
-high/broad nasal root
-irisis can be different colors
222
what are some integumentary findings in warrdenburg 1 ?
-white forelocks
(partial albinism)
-premature graying of hair, eyebrows, and lashes
- frequency of occurrence of these range from 10-30%
223
what are some audiologic findings in waardenburg 1?
-Bilateral or unilateral hearing loss of variable severity occurs in association with defects of neural crest cells
-The hearing loss can be profound with a corner audiogram or a moderate hearing loss in the low to mid frequencies
-Vestibular abnormalities are reported
-Atrophic changes in the spiral ganglion and VIII nerve
-Degeneration of the organ of corti
-Thickening of the basal membrane
224
what are waardenburg syndrome 2 look like ?
-The same as type I except there is no lateral displacement of the inner angles of the eye
-Unilateral hearing loss is less prevalent than in WS1
225
what is seen in waardenburg type 3
upper skeletal extremities abnormalities
226
what are 2 things to know about waardenburg 4 syndrome ?
-deafness
-Hirschsprung disease
A disorder of intestinal motility characterized by the absence of parasympathetic plexuses of the gut
-Aganglionic megacolon
-absence of the neural crest cells, the colon can't contract but can expand
-Constipation
227
what are the most common autosomal dominant syndrome?
1)waardenburg syndrome
2) branchio-oto-renal (BOR)
228
what are the most common recessive syndrome ?
1)ushers
2)pendreds
3)jervell and lange nielsen syndrome (JLNS)
229
what conditions contribute to ear changes ?
-treacher collins, branchio-oto-renal syndrome
230
what conditions are involved with eye disease?
-ushers, norrie
231
what conditions involve musculoskeletal issues
crouzon syndrome
sticklers
232
what issues involve renal issues
alports
233
what issues involve cardiac issues
jernells lange nielson
234
what conditions involve neurologic/neuromuscular systems
friedreich ataxia
235
what conditions involve issues with the endrocrine issues
pendreds
236
what conditions involve metabolic issues ?
biotinidase deficiency
muccopolysacharidoses
237
what issues involve the intergumentary system?
waardenburg
238
what condition doesn't involve mental or physical conditions
connexin hearing loss and deafness
