Transcript Genetic Causes of Deafness

Genetic Causes of Deafness
Genetic factors are responsible for
50-60% or more of children dx with hearing loss.
More than 400 types of genetic deafness
Newly developed genetic testing improved
situations
Progress understand biochemical/molecular
characteristics of genes involved with the
composition of hearing mechanism & clinical
effects many types of hereditary deafness.
Practical applications of
Knowledge
Improved genetic testing
More access to genetic counseling
(deaf individual and deaf families)
1/3 genetic deafness is syndromic loss in
combination with medical or physical
characteristics
Rest is nonsyndromic.
(individuals with genetic deafness inherit only
the trait of hearing loss)
Genetic Transmission of Deafness
DNA
Autosomal Dominate Inheritance
Autosomal Recessive Inheritance
X-linked Recessive Inheritance
Mitochondrial Inheritance
Deoxyribonucleic Acid (DNA)
DNA -is a nucleic acid that contains the genetic
instructions used in the development and functioning of
all known living organisms.
The main role of DNA molecules is the long-term
storage of information and DNA is often compared to a
set of blueprints, since it contains the instructions
needed to construct other components of cells, such as
proteins and RNA molecules.
The DNA segments that carry this genetic information
are called genes, but other DNA sequences have
structural purposes, or are involved in regulating the use
of this genetic information.
Autosomal Dominate Inheritance
means that the gene carrying a mutation is
located on one of the autosomes (chromosome
pairs 1 through 22).
This means that males and females are equally
likely to inherit the mutation.
"Dominant" means that having a mutation in just
one of the two copies of a particular gene is all it
takes for a person to have a trait, such as an
increased risk of developing cancer
Autosomal Dominate Inheritance
Most genes come in pairs, one of which is
inherited from the mother and the other from the
father.
A mutation is a change in a gene that prevents it
from working properly. Mutations in genes are
inherited from our biological parents in specific
ways.
When a parent has a dominant gene mutation,
there is a 50 percent chance that any child
he/she has will also inherit the mutation.
Autosomal Dominant Inheritance
Autosomal Recessive Inheritance
means that the gene carrying the mutation is
located on one of the autosomes (chromosome
pairs 1 through 22).
This means that males and females are equally
affected.
"Recessive" means that both copies of the gene
must have a mutation in order for a person to
have the trait.
Autosomal Recessive Inheritance
One copy of the mutation is inherited from the mother,
and one from the father.
A person who has only one recessive gene mutation is said
to be a "carrier" for the trait or disease, but he/she does
not have any health problems from carrying this one
mutation. Most people do not know they carry a recessive
gene mutation for a disease until they have a child with
the disease.
Once parents have had a child with a recessive disease,
there is a one out of four, or 25 percent chance, with
each subsequent pregnancy, for another child to be born
with the same disorder.
This means that there is a three out of four, or 75
percent chance, for another child to not have the disease
Autosomal Recessive Inheritance
X-linked Recessive Inheritance
These genetic diseases are diseases caused by
an error in a single DNA gene.
X-linked means the error occurs on the X
chromosome which is the 23rd sex-linked X
chromosome.
Such diseases are sometimes called "sexlinked" rather than X-linked.
Mitochondrial Inheritance
are normal structures or organelles in cells.
They are located in the cell's cytoplasm outside
the nucleus. Are responsible for energy
production convert nutrients into energy as well
as doing many other specialized tasks.
Each mitochondrion has a chromosome that is
made of DNA but is otherwise quite different
from the better known chromosomes in the
nucleus.
Mitochondrial Inheritance
The inheritance of a trait encoded in the
mitochondrial genome. Because of the oddities
of mitochondria, mitochondrial inheritance does
not obey the classic rules of genetics.
Persons with a mitochondrial disease may be
male or female but they are always related in
the maternal line and no male with the disease
can transmit it to his children.
Major Genetic Syndromes Involving Deafness
Pendred Syndrome
Branchial-Oto-Renal Syndrome (BOR)
Jervell and Lange-Nielsen Syndrome
Neurofibromatosis Type 2 (NF-2)
Stickler Syndrome (SS)
Treacher-Collins Syndrome
Usher Syndrome
Pendred Syndrome
genetic disorder that causes early hearing loss in
children.
Children may begin to lose their hearing at birth or by
the time they are three years old.
Usually, their hearing will worsen over time.
The loss of hearing often happens suddenly, although
sometimes some hearing will be restored afterwards.
Eventually, some children with Pendred syndrome
become totally deaf.
Branchio-Oto-Renal Syndrome
autosomal dominant disorder
main clinical features include branchial derived
anomalies, otologic anomalies, and renal
malformation
hearing loss found in BOR is highly variable
loss can be sensorineural, conductive or mixed
can be stable or progressive and the severity
can range from mild to profound
BOR
Ear pits are found in about 80%
individuals have deformed outer-ear(s), middleear(s), and/or inner-ear(s)
60% of the BOR cases have branchio cysts or
fistulas which are small holes located on the
front, external lower third of the neck
Jervell and Lange-Nielsen Syndrome
condition that causes profound hearing loss
arrhythmia, it is a type of long QT syndrome.
heart condition that causes the cardiac
muscle to take longer than usual to recharge
between beats
untreated, the irregular heartbeats can lead
to fainting, seizures, or sudden death.
Neurofibromatosis Type 2
disorder characterized by the growth of
noncancerous tumors in the nervous system.
common tumors associated vestibular
schwannomas or acoustic neuromas
growths develop along the nerve that
carries information from the inner ear to
the brain (the auditory nerve)
Neurofibromatosis Type 2 signs and
symptoms
appear during adolescence or in a person's
early twenties, although onset can occur at
any age
most frequent early symptoms of vestibular
schwannomas are hearing loss, ringing in the
ears (tinnitus), and problems with balance
Stickler Syndrome (SS)
Hereditary progressive arthro-opthalmopathy
group of hereditary conditions characterized by
a distinctive facial appearance, eye
abnormalities, hearing loss, joint problems, cleft
palate, vision problems, i.e., myopia or retinal
detachment.
Treacher-Collin Syndrome
Mandibulofacial dysostosis and FrenceshettiKlein
rare inherited condition characterized by
bilateral and symmetric abnormalities of
structures within the first and second bronchial
arches
Treacher Collins Syndrome, or
Francheschetti-Klein Syndrome
genetic disorder, inherited as an autosomal-dominant
trait and characterized by some or all of the following:
underdevelopment of the cheek and jaw bones
widely separated eyes
malformation of the lower eyelid and lack of eyelashes
malformation of the ear auricle
lack of an external ear canal with resultant conductive
deafness, and other, less common abnormalities
Usher Syndrome
most common condition that involves
both hearing and vision problems
Deaf/blindness
Major symptoms of Usher Syndrome
hearing impairment
retinitis pigmentosa-eye disorder that
causes a person's vision to worsen over
time
Waardenburg Syndrome
inherited disorder often characterized by
varying degrees of hearing loss and changes in
skin and hair pigmentation
One commonly observed characteristic of
Waardenburg syndrome is two differently
colored eyes
One eye is usually brown and the other blue
Sometimes, one eye has two different colors
may have unusually brilliant blue eyes
Types of Waardenburg syndrome
Cause of Waardenburg syndrome
genetic disorder
passed down from parent to child much like
hair color, blood type, or other physical traits
dominant condition, a child usually inherits
the syndrome from just one parent who has
the malfunctioning WS gene