Achondroplasia Genetic Disorder

What is Achondroplasia?

Achondroplasia

Who is Affected?

• equal within gender and sex
• estimated frequency: 1 in 15,000 to 1 in 35,000 births
• approximately 5 million people in the US
• 40% under 21 years old
• risks increases as the father gets older
• last child more likely than first child

Symptoms

Mode of Inheritance

• autosomal dominant
• 80% of people with this disorder have parents normal size; not inherited
• 20% cases are inherted
• One Parent --> 50% chance of normality
• Both Parents --> 25% chance of normality

• Bone growth disorder
• Short height
• Normal torso with short limbs
• ex. short upper arm and thigh
• Large head compared to body
• Short fingers that point in weird directions
• Less muscle tone/slowed motor skills
• Conditions that may develop:
• bowed limbs
• obesity
• abnormal spine curvature

Mutation

• Over 80% of cases are NOT inherited -
• --> spontaneous mutation in FGFR3 gene
• Gene becomes too active, disturbs bone growth
• Other 20% of disease cases ARE inherited
• --> autosomal dominant
• At least one parent must have the condition for the child to have it
• FGFR3 gene (fibroblast growth factor receptor 3): plays an important role in cell determination, cell growth, formation of vessels
• Makes proteins that are found in cells that grow bone tissue

Diagnosis

During Pregnancy

• Ultrasound
• hydrocephalous
• Amniotic Fluid samples

After Childbirth

• X rays
• length of bones
• Blood tests

Why?

Ethical Concerns

• Do you want to know this information?
• Who owns this information? Who is it allowed to have it?
• How will this affect people's choice to have offspring?
• Consent in regards to wanting testing and not wanting testing, ripple effect

Possible Future Treatments

• Basics: tests designed to extract DNA and analyze genes
• Purpose:
• To diagnose diseases
• Find out gene changes after a disease starts
• Determine how gene changes might affect offspring
• Screen individuals for potential future diseases

Treatments

Predicting Possible Genotypes

Clinical BioMarin Dug Trial (BMN-111)

• block effects of too much signaling from the FGFR3 mutation because it is a receptor
• growth in spinal canal, bones, the foramen magnum and head and face changes

Decoy Protein

• synthetic form of FGFR3=sFGFR3
• kept the mutant gene receptor from functioning

Gene Therapy

• recombinant protein therapy
• block the overactivation of the receptor in the developing growth plate
• employ the decoy protein

Predicting Genotypes (cont.)

• If one parent is affected and heterozygous and the other is unaffected (previous picture)
• 1:1 genotype ratio of Aa : aa
• If both parents affected + heterozygous
• 1:2:1 genotype ratio AA: Aa : aa

Genetic Testing

Predicting Possible Phenotypes

Current Treatments

• If the parents are both heterozygous
• 1/4 would be normal (aa)
• 1/2 have condition (Aa)
• 1/4 have fatal condition (AA) (stillborn/diereally quickly)
• If one parent is heterozygous and one homozygous recessive
• 1/2 would be normal (aa)
• 1/2 would have disease (Aa)

• No specific cure or treatment
• Use growth hormones to increase the growth rate
• Vertical Expandable Prosthetic Titanium Rib
• bone lengthening surgery

Infants with achondroplasia usually have these problems:

• Apnea
• Compression of spinal cord
• Hydrocephalus

Works Cited

• "Achondroplasia." Genetics Home Reference. N.p., 14 Mar. 2016. Web. 17 Mar. 2016. <https://ghr.nlm.nih.gov/condition/achondroplasia>.
• "Achondroplasia - NORD (National Organization for Rare Disorders)." NORD National Organization for Rare Disorders Achondroplasia Comments. 2015. Web. 17 Mar. 2016. <http://rarediseases.org/rare-diseases/achondroplasia/>.
• "ETHICAL ISSUES IN HUMAN GENETICS AND GENOMICS." Genetics.edu.au. Centre for Genetics Education, 26 Feb. 2016. Web. 17 Mar. 2016. <http://www.genetics.edu.au/Publications-and-Resources/Genetics-Fact-Sheets/FactSheetELSI>.
• Fallon, L., "dwarfism." The Columbia Encyclopedia, 6th Ed.. 2015, "Dwarfism." Allusions--Cultural, Literary, Biblical,;Historical: A Thematic Dictionary. 1986, "Dwarfism." Complete Human Diseases;Conditions. 2008, "dwarfism." A Dictionary of Nursing. 2008, and "dwarfism." A Dictionary of Biology. 2004. "Dwarfism." Encyclopedia.com. HighBeam Research, 2006. Web. 17 Mar. 2016. <http://www.encyclopedia.com/topic/dwarfism.aspx>.
• "FAQ About Genetic Testing." FAQ About Genetic Testing. National Human Genome Research Institute, 27 Aug. 2015. Web. 17 Mar. 2016. <https://www.genome.gov/19516567>.
• "FGFR3 Gene." Genetics Home Reference. N.p., n.d. Web. 17 Mar. 2016. <https://ghr.nlm.nih.gov/gene/FGFR3>.
• Kivi, Rose. "Achondroplasia." Healthline. N.p., 11 Dec. 2015. Web. 17 Mar. 2016. <http://www.healthline.com/health/achondroplasia#Diagnosis6>.
• "Achondroplasia." Achondroplasia. N.p., n.d. Web. 17 Mar. 2016. <http://www.marchofdimes.org/complications/achondroplasia.aspx#>.
• Okenfuss, Ericka. "Emerging Research and Potential Treatments in Achondroplasia and Other Skeletal Dysplasias." Research and Treatments. N.p., n.d. Web. 17 Mar. 2016. <http://www.lpaonline.org/research-and-treatments>.
• Krans, Brian. "A Decoy Protein Could Cure Dwarfism." Healthlines RSS News. N.p., 18 Sept. 2013. Web. 17 Mar. 2016. <http://www.healthline.com/health-news/children-decoy-protein-could-cure-achondroplasia-dwarfism-091813>.
• "Community Research and Development Information Service - CORDIS." European Commission : CORDIS : Projects & Results Service : Gene Therapy for Achondroplasia. N.p., 17 June 2015. Web. 17 Mar. 2016. <http://cordis.europa.eu/result/rcn/89531_en.html>.

Pictures

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