Genetic Hearing Loss with Other Abnormalities Flashcards
What is Otopalatodigital?
X-linked recessive disorder that affects bone and facial structures
Full expression in males
What are the features of Otopalatodigital? (5)
- Ear anomalies
- Cleft palate
- Finger and toe anomalies
- Craniofacial anomalies
Broad nasal root
Pierre Robin sequence - CHL (ossicular malformations)
What is Crouzon?
Crouzon syndrome, also known as Craniosynostosis, is a genetic syndrome in which the seams of the skull fuse abnormally.
AD
FGFR2 mutation
Midface hypoplasia
Hyperterlorism, exorbitism
CP
CHL, mixed HL
Ossicular anomalies
How can we fix Crouzon syndrome?
Surgical craniofacial reconstruction
What is Apert syndrome? (acrocephalosyndactyly)
Apert syndrome, also known as acrocephalosyndactyly, is a genetic disorder that causes the fusion of the skull, hands, and feet bones.
Autosomal Dominant
Sporadic (>90%)
FGFR2 mutation
Craniosynostosis
Similar to Crouzon
CHL
Syndactyly
What is Syndactyly?
Fused digits
What is Osteogenesis Imperfecta
Systemic disorder of connective tissue with abnormal bone formation
AD or AR
Spontaneous mutation
What are the symptoms of Osteogenesis Imperfecta? (8)
Bone fractures
Low muscle tone
Loose joints
Blue sclera
Brittle teeth
Short stature
Respiratory problems
CHL, SNHL, mixed
What is the Marfan syndrome?
Marfan syndrome is a genetic condition that affects connective tissue, which provides support for the body and organs
AD
Tall, long-limbed
Pectus excavatum
Scoliosis
Joint laxity
Mixed HL
What is Hemifacial Microsomia?
- Hemifacial microsomia is a congenital condition in which the tissues on one side of the face are underdeveloped
- Aka oculoauriculovertebral spectrum
Goldenhar syndrome refers to severe form of hemifacial microsomia - Branchial arch developmental anomaly
- Can be bilateral
Differing degrees in each half - May occur with other syndromes
What is Goldenhar Syndrome?
Goldenhar syndrome refers to severe form of hemifacial microsomia
A rare congenital condition characterized by abnormal development of the eye, ear and spine
Sporadic and AR
What are features of Goldenhar syndrome?
Hemifacial microsomia
Preauricular pits/tags
Epibulbar dermoids
Colobomas
Cervical spine fusion
What is Usher syndrome?
Usher syndrome is a rare genetic disease that affects both hearing and vision. It causes deafness or hearing loss and an eye disease called retinitis pigmentosa (RP).
What can Usher syndrome cause?
- AR
- Bilateral SNHL
- Retinitis pigmentosa
- Vestibular defects
- Diagnosis
Electroretinography - 5% of congenital HL
What is Retinitis pigmentosa?
Retina becomes pigmented/stained and scarred
Sensory cells of the eyes gradually deteriorate
Leads to tunnel vision and eventual blindess
What are the effects of Usher on hearing?
No cure for eye and balance problems
Early CI for SNHL
Supportive: braille, counseling, sign language,…
What is stickler?
Aka arthro-ophthalmopathy
AD
Collagen mutation (COL2A1 gene)
What are anomalies seen in Stickler?
- Craniofacial
- Arthropathic
- Hearing loss
- Craniofacial
Pierre Robin sequence (30%)
Micrognathia
Cleft palate - Midface hypoplasia
- Ocular anomalies
Myopia
Glaucoma
Cataracts
Retinal detachment
What are Musculoskeletal anomalies in Stickler? (5)
Osteoarthritis
Joint hypermobility
Vertebral abnormalities
Scoliosis
Marfanoid habitus (tall, thin)
What are the hearing loss types from Stickler?
Mild-moderate SNHL (80%)
Mixed (15%)
CHL due to eustachian tube dysfunction related to cleft palate
(Ossicular abnormalities)
What is Norrie?
- X-linked recessive disorder
*Eye
Cataracts
Leukocoria
Blindness - Ear
Progressive SNHL - Developmental problems
What is Norrie?
- X-linked recessive disorder
*Eye
Cataracts
Leukocoria
Blindness - Ear
Progressive SNHL - Developmental problems
What is KID syndrome?
Keratitis
Ichthyosis
Deafness
What is Keratitis?
Inflammation leading to destruction of cornea (may cause blindness)
What is Ichthyosis?
Generalized skin disorder of dryness, roughness and scaliness (red thickened skin)
Which HL is associated with KID?
Deafness
SNHL (usually severe/profound)
What is Waardenburg syndrome?
Group of genetic conditions that can cause hearing loss and changes in coloring (pigmentation) of the hair, skin, and eyes.
AD, variable penetrance (some AR)
Most common type of syndromic AD SNHL
2% of congenitally deaf children
What are the features of Waardenburg?
White forelock
Hypoplastic alae
Short philtrum
Heterochromia irides
Synophyrs
Dystopia canthorum
What HL is associated with Waardenburg?
SNHL
Mild to profound
Unilateral or bilateral
Typically not progressive
Amplification or CIs
4 types
What constitutes LEOPARD?
Lentigines
ECG abnormalities
Ocular hypertelorism
Pulmonary stenosis
Abnormal genitalia
Retarded growth
Deafness
What is Lentigines?
Multilple brown skin lesions
What are ECG abnormalities?
Cardiac conduction problems
What is Ocular hypertelorism?
Widely set eyes
What is special about Dalmatians? (3)
Most are born pure white and develop colored patches
High susceptibility to rashes, skin diseases and irritations
Genetic integumentary disorder
What can happen to the hearing of Dalmatians?
- Deafness is common
8% bilateral SNHL
20% unilateral SNHL - It is recommended that all Dalmatian puppies undergo ABR
What are Metabolic Disorders? (3)
Any disorder that involves an alteration of the normal metabolic process
- Common example-diabetes
What is Mucopolysaccharidosis?
- Lysosomal storage disorder
- Lysosome-carries enzymes that break down large proteins
- Defect leads to only partial breakdown of polysaccharides
What are enzymes?
Enzymes are proteins that help speed up metabolism, or the chemical reactions in our bodies. They build some substances and break others down. All living things have enzymes
What are polysaccharides?
. They are long chains of carbohydrate molecules, composed of several smaller monosaccharides (sugar, glucose etc.)
What are the 7 types of Mucopolysaccharidosis?
- Depends on what enzyme is defective
- I and II most common
- Most have significant eustachian tube dysfunction
What are the features of Hunter (I) and Hurler (II) and Mucopolysaccharidosis? (6)
Dwarfism
Short neck
Macroglossia
Large tonsils/adenoids
Craniofacial anomalies (coarse facial features)
Airway obstruction (OSA)
What are the conditions in Hunter (l)?
AR
Progressive, moderate SNHL
CHL
What are hearing disorders in Hurler (II)?
X-linked
50% moderate SNHL
CHL
What is Pendred syndrome?
AR (chromosome 7)
Abnormal thyroid gland metabolism-tyrosine iodination defect leading to abnormal thyroxine biosynthesis
Presents with:
Thyroid goiter
SNHL
What can we see at the Vestibular Aqueduct in Pendred?
What is a typical case in Pendred?
5 yo boy who passed newborn hearing screen
3 episodes of fluctuating hearing loss (unilateral or bilateral)
Goiter appeared around age 8 yo
Hearing loss progress to bilateral severe SNHL
What is Turner’s syndrome?
Turner syndrome, a condition that affects only females, results when one of the X chromosomes (sex chromosomes) is missing or partially missing
Karyotype-45 XO (monosomy)
Increased incidence of SNHL and CHL
What HL can Turner cause?
- CHL
Eustachian tube dysfunction (shorter and more horizontal) OM
EAC anomalies
Many will require ear tubes - SNHL
Usually mild to moderate
Amplification
What are the symptoms of Jervell and Lange-Nielsen?
- AR
- Bilateral SNHL
Profound and high frequencies
Stria vascularis defect - Prolonged QT on ECG
Recurrent syncope
Sudden death
Family history
What are features of Jervell and Lange-Nielsen?
- Extremely rare
- Over 50% of untreated patients die of cardiac disease before age of 15 years
- Hearing loss may be the only initial sign
ECG is ordered on all congenital SNHL - Management
Pacemakers, beta-blockers
Hearing aids/CI
Genetic counseling
What is Alport syndrome?
Alport syndrome is a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities. People with Alport syndrome experience progressive loss of kidney function
What are characteristics of Alport?
- X-linked recessive (80%)
Type IV collagen abnormality
Males more severely affected
AR (20%) - Collagen
Connective tissue that provides support and strength
Type IV collagen found in kidneys, ears, and eyes
What are the features of Alport Syndrome? (3)
- Progressive SNHL
Onset usually during 2nd decade of life - Renal
Progressive glomerulonephritis - Ocular
Myopia, cataracts - Normal appearance
What is Branchio-Oto-Renal? (2)
- Branchial arch developmental abnormality
- 1st and 2nd arches are involved
- Branchial cleft cysts and fistulae common (presents as neck masses)
What abnormalities present with Branchio-Oto-Renal condition?
- Aka Melnick Fraser
- AD with variable expression
- Pre-auricular pits, tags
- External ear deformities
Microtia
Prominent ears
What hearing features do we see from Branchio-Oto-Renal conditions?
- Renal
Mild dysplasia to agenesis - SNHL, CHL, or mixed
- Ossicular anomalies
- Cochlear anomalies (Mondini)
What is Trisomy 21?
Down Syndrome
From Extra chromosome 21
Increased risk with advanced maternal age (increasing incidence)
Most common cause of intellectual disability
Most common chromosomal abnormality
What is the incidence and life expectancy of Trisomy 21?
- Incidence
Overall, 1 in 800 live births
Mother < 35 yo, 1 in 1500
Mother > 35 yo, 1 in 100
*Life expentancy
50% survive into 50’s
15% survive into 60’s
What are the craniofacial features of trisomy 21?
Brachycephaly
Flat occiput
Epicanthal folds
Upslanting palpebral fissures
Short, flat, small nose
Small, low-set ears
Short neck
Brushfield spots
How can Trisomy 21 affect the Eustachian Tube?
- Abnormal craniofacial skeleton
- COME -> CHL
- CHL from other causes (small EAC, ossicular anomaly)
- SNHL
Many will get ear tubes
What is the CHARGE acronym?
Coloboma
Heart defects
Atresia choanae
Retarded growth
Genitourinary anomalies
Ear anomalies
What causes CHARGE?
- Defect in CHD7 gene on chromosome 8
Other defects and causes possible - Rare disorder (1 in 10,000)
- Prognosis
25% die within first 3 months
Tremendous individual variability
Early detection and treatment leads to improved function
What is Coloboma?
- Defect in structures of the eye
- Developmental anomaly resulting from the failure of closure of certain structures (eyelids, lens, iris, optic disc)
What is Choanal atresia?
- No opening from nasal cavity to nasopharynx
- Bilateral atresia in newborns leads to airway obstruction
What is Ear anomalies?
- External, middle, and inner ear problems
- CHL, SNHL or mixed
What do CHARGE-Ear Anomalies cause in the external ear?
Microtia, cup/lop ears, malposition
What do CHARGE-Ear Anomalies cause in the Middle ear?
- Absent/abnormal ossicles and oval/round windows
- Middle ear effusions
What do CHARGE-Ear Anomalies cause in the Inner ear?
Hypoplasia of CN7, cochlea
Temporal bone anomalies
What do CHARGE-Ear Anomalies cause in hearing?
- Prevalence ≥ 90%
- Usually mixed (CHL + SNHL)
Mild to profound
May be progressive
Most have sloping loss greatest in high frequencies
How do CHARGE anomalies affect Hearing Aids?
- Difficulty fitting earmolds due to external ear malformations and small EAC
- Chronic infection or otorrhea may also prevent hearing aid use
What is Neurofibromatosis (Type 1)?
- Autosomal dominant
Neurofibromin gene (NF1) on chromosome 17
Half from new mutation - AD-variable expression
- Better prognosis than Neurofibromatosis Type 2
What does Neurofibromatosis, Type 1 cause on the body?
Café au lait spots
Cutaneous neurofibromas
Plexiform neuromas
Lisch nodules
Axillary or perineum freckling (Crowe sign)
Optic gliomas
Bone abnormalities
What is Neurofibromatosis, Type 2?
- Autosomal dominant
NF2 (Merlin) gene on chromosome 22
Approximately 10% of all individuals with neurofibromatosis - Significant morbidity, decreased lifespan
What does Neurofibromatosis, Type 2 cause?
- Café au lait spots
- Schwannomas
Bilateral acoustic neuromas
Spinal cord
Nonvestibular - Subcapsular cataracts
- Meningiomas
