1. ACHONDROPLASIA Madhurima Yerra Mr. Steinman Honors Biology A4

2. Achondroplasia is a type of short-limbed dwarfism. It occurs when the process by which cartilage is converted to bone, or ossification, is stunted. This is most apparent in the long bones of the arms and legs. What is Achondroplasia?

3. The Cause Achondroplasia is an autosomal dominant mutation, which means that one copy of the changed gene is enough to cause the condition. Achondroplasia is due to mutations of the FGFR3 gene on the short arm of chromosome 4. This gene regulates bone development, so when affected, it causes malfunctions in bone growth. During the formation of proteins, only a single amino acid is substituted, but it obviously seems to be a vital piece. To the left is a diagram of chromosome 4. The location of the FGFR3 gene is indicated by the yellow arrow.

4. Symptoms Short arms and legs: particularly the upper arms and thighs Enlarged head (macrocephaly) Prominent forehead Short fingers: the middle and ring fingers may diverge, giving the hand a three-pronged (trident) appearance Apnea: when breathing slows or stops for short periods of time Persistent ear infections Lordosis: a pronounced and prominent curvature of the lower back- compresses the spinal cord Bowed legs Mid-face hypoplasia: undergrowth of the mid-face Hypotonia: low and weak muscle tone Delays in walking and other motor skills Back pain Obesity Bowed legs Limited range of motion at the elbows

5. Diagnosis Characteristic clinical results X-ray findings Genetic testing: for individuals that are too young to make a definite diagnosis or do not have typical symptoms

6. Treatment There is no specific or permanent treatment available for achondroplasia. From birth, the height, weight, and head circumference of affected children are closely monitored, and measures to avoid obesity are taken. To further evaluate hypotonia or signs of spinal cord compression, a magnetic resonance imaging (MRI) or computed tomography (CT) scan will be needed. To help with breathing, there are surgeries to remove the adenoids and tonsils. Also, continuous positive airway pressure (CPAP) by nasal mask can be done. To correct obstructive sleep apnea, a surgical opening in the airway, or tracheostomy, can be performed. With patients with problems such as hyperreflexia (overactive reflexes), clonus (a series of involuntary muscle contractions and relaxations), or central hypopnea (reduction in respiratory effort leading to a reduction in airflow), there is a surgery called suboccipital decompression, which decreases pressure on the brain. Growth hormones and/or surgery may be able to lengthen limbs, but only up to a point.

7. Impact on Living a “Normal” Life In most cases, achondroplasia has not stopped the people that are affected from living normal lives. Other than their size and various health issues, there are no other obstacles. Ivy Broadhead, a writer for The Evening Chronicle, is a person who has the condition and extraordinarily describes life with achondroplasia. “We are born, eat, sleep, breathe, work, study, marry, have children, get ill, and die, just like everyone else.” ~ Ivy Broadhead In term of health, there will be the common back pain, but most will not experience the more serious of the sympotoms. These people feel no shame in asking for help. They develop climbing abilities and use whatever they can find to reach for up high items. At home, they will typically have step stools and few house alterations, such as lower locks for doors. Driving is also not a big issue, as it is possible to do so with pedal extensions. The hardest part is the ridicule. They do not mind the innocent curiosity of children, but it is insulting when it comes from older people.

8. Research Outlook Scientists are studying how the features of achondroplasia are caused by abnormalities in the structure or function of the FGFR3 gene. One specific study is on the interactions between the FGFR3 gene and a cell-to-cell signaling pathway that plays a role in bone development. Their main goal is to develop treatments for achondroplasia and other skeletal disorders caused by this gene.

9. For Additional Information… Living with Achondroplasia: Ivy Broadhead's Story ChronicleLive.co.uk- Take an inside look into one woman’s life with achondroplasia. Achondroplasia Genetics Home Reference- This database gives a thorough explanation of achondroplasia and its effects.

10. Interesting Facts KEY SQUARE- Male CIRCLE- Female SHADED- Affected UNSHADED- Unaffected A horizontal line indicates mating. A vertical line that later branches off, indicates offspring. I, II, and III indicate the generations This pedigree (autosomal dominant) follows the transmission of achondroplasia in a family.

11. Interesting Facts cont. Average height of males: 131 cm (4 feet, 4 inches) Average height of females: 124 cm (4 feet, 1 inch) Normal intelligence Offspring that received the mutated FGFR3 gene from both parents (homozygous dominant) will not survive past infancy. Two unaffected parents can still have a child with the mutated gene, but this is rare. If only one parent is affected, there is a 50-50 chance of having a normal or affected child. If both parents are affected, there is a 50% chance of have a child that is affected, a 25% chance of having a child that is normal, and a 25% chance of having a child that will die soon after birth. Happens in every 1 in 15, 000 to 1 in 40, 000 live births.

12. THIS IS ACHONDROPLASIA! THANK YOU!  