Transcript Gabriela Guia Dwarfismx

Dwarfism
“Achondroplasia”
GABRIELA GUIA
BIOLOGY 1407
Introduction
 Unfortunately not everyone is born healthy and
normal.
 We do not have control over our chromosomes and
genes.
 Sometimes they undergo mutations that can cause
a fatal result of the embryo, diseases, or even
achondroplasia.
What is Achondroplasia ?
 Achondroplasia: is
the most common form
of short-limbed dwarfism
in humans
 It is caused by mutations
in the fibroblast growth
factor receptor gene 3
(FGFR3)
 Or it can also be
inherited from an
affected parent.
What is FGFR3?
 FGFR3 gene provides
instructions for making a
protein that is involved
in the development and
maintenance of bone and
brain tissue.
 FGFR3 has a negative
regulatory effect on bone
growth.
What is FGFR3?
 It determines cell type, formation of blood vessels,
wound healing, and embryo development.
 The penetrance of the gene is 100%, meaning that
all individuals who have a single copy of the altered
FGFR3 have achondroplasia.
FGFR3
 People with achondroplasia have one normal
copy of the fibroblast growth factor receptor 3
gene and one mutant copy.
 Only 1 copy of the gene needs to be present for
the disorder to occur.
Achondroplasia
 2 mutations in the FGFR3 gene, a G-to-A
transition at nucleotide1138 and a G-to-C
transversion at the same nucleotide, both resulting
in G380R amino acid substitutions, cause over
99% of cases of achondroplasia.
Achondroplasia
There are over 200 types of dwarfism, the most
common type is achondroplasia.
 Achondroplasia occurs in one of every 25,000
people.
Did You Know?
 More than 80% of
individuals with
achondroplasia have
parents with normal
stature
 And have
achondroplasia as a
result of a de novo
gene mutation.
De Novo Gene Mutation
 Associated with increasing paternal age(over
35 years).
 Studies demonstrate that new gene
mutations are inherited from the father and
occur during spermatogenesis
Diagnosis
 Detected before birth
by prenatal
ultrasound.
 DNA test before birth
to detect
homozygosity (where
two copies of the
mutant gene are
inherited)
Achondroplasia Average Height
 Male adult height is 131 cm (4 feet, 3-
1/2 inches)
 Female adult height is 123 cm (4 feet,
1/2 inches)
Physical Features
 Proximal
shortening of the
extremities
Physical Features
 Genu Varum
(bow-leggedness)
 It’s a deformity
marked by medial
angulation of the
leg
Physical Features
 Trident hand
 Limited elbow
extension
 Exaggerated
lumbar lordosis

an excessive inward curve
of the spine
Physical Features
 Megalencephaly
 Characteristic
facies with frontal
bossing and
midface
 Hypoplasia
Radiological Features
 Small cuboid vertebral
bodies with progressive
narrowing of the caudal
interpedicular distance
 Thoracolumbar
kyphosis with
occasional anterior
beaking of the first and
second lumbar
vertebrae
Radiological Features
 Small iliac wings
with a narrow
greater sciatic
notch
 Short tubular bones
with metaphyseal
flare and cupping
Possible Genotypes for the Parents
 If an RR mother, and an
RR father produce
offspring, 100% of their
children will have
dwarfism.
 If both of the parents are
Rr then 75% of their
children will have
dwarfism.
Possible Genotypes for the Parents
 If one parent is RR and
the other parent is Rr
then all of their children
will have dwarfism.
 Also if the mother is Rr
and then father is rr then
at least 50% of their
children will have
dwarfism.
Family Outcome with Dwarfism
Facts
 Children with two
achondroplasia alleles
have a severe phenotype.
 These children
experience respiratory
insufficiency, brainstem
compression, and severe
neurologic deficits.
 Most usually die within
the 1st year of life
Medical Complications
 Delayed motor
milestones
 Communicating
hydrocephalus
Medical Complications
 Secondary to a small
foramen magnum
A
great hole in the
occipital bone
through which the
medulla oblongata
(extension of spinal
cord) enters and
exits the skull
Medical Complications
 Frequent
sinusitis
 Otitis media Inflimation
of
the middle ear
Medical Complications
 Apnea  suspension
of
external breathing.
 During apnea there
is no movement of
the muscles of
respiration and the
volume of the lungs
initially remains
unchanged.
Medical Complications
 Spinal stenosis
 Many orthopedic
problems
Surveillance
 Adults are at
increased risk for
spinal stenosis.
 A clinical history and
neurologic
examination is needed
every 3 to 5 years.
Achondroplasia Mothers and Birth
 Mothers in labor must
always be delivered by
Caesarian section.
 Because of the small
size of the pelvis in
affected women.
Life Expectancy
 Length of life varies,
depending on their
condition.
 The youngest has died
at age 20.
 Many live normal
lives like regular
humans that have
recessive alleles
Life Expectancy
 Life span of affected
people with
achondroplasia in the
United States is 80 yrs.
 Where as in other parts
of the world (third world
countries) the average
life expectancy, with
achondrioplasia, is age
70.
Achondroplasia Video Clip
 httwww.youtube.com/watch?v=AZP8DWCfnh4p://
Please right click on link and choose “Open
Hyperlink”
Socialization
 Due to the visible nature of the short stature,
affected persons and their families may encounter
difficulties in socialization and school adjustment.
 Support groups, such as the Little People of
America, Inc (LPA), can assist families with these
issues.
Little People of America (LPA)
 LPA helps with:
 Information on employment, education, disability
rights, etc.
 Medical issues
Little People of America (LPA) Continued
 Suitable clothing
 Adaptive devices
 Parenting seminars and workshops.
Treatment
 There is not a
treatment for
achondroplasia at this
time.
 However, people with
achondroplasia may
undergo a surgery of
limb lengthening,
which will lengthen
their legs and arms.
Did You Know???
 Some animals can
also be dominant
for dwarfism
References
 http://en.wikipedia.org/wiki/Achondroplasia
 http://www.pubmedcentral.nih.gov/picrender.fcgi?a
rtid=1801129&blobtype=pdf
 Biology 8th edition