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 Achondroplasia occurs in one of every 25,000 people. 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)

Proximal shortening of the extremities 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?artid=1801129&blobtype=pdf Biology 8th edition