Achondroplasia Research Paper
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Mick St John
April 8, 2013
Achondroplasia (Dwarfism)
One in every 15,000 to 40,000 people have Achondroplasia. This means that over 466 million people on the planet have Achondroplasia. Achondroplasia is a genetic disorder that is a part of a group of disorders called chondrodystrophies or osteochondrodysplasias. Achondroplasia literally means
"without cartilage formation". Cartilage is a strong and flexible tissue that makes up most of the skeleton during a child’s early development, without it, the child has no chance of growing properly (Genetics
Home Reference). This disorder is passed down through family generations, it is a dominant trait that one or both parents can carry and if one parent has it, in almost every case, the child inherits this …show more content…
disorder. If one parent carries the gene mutation, the child has a 50% chance of inheriting it. If both parents carry it, then the child has a 75% chance of being born with this disorder. In some rare cases, neither of the parents carry the disorder, but the child is still born with Achondroplasia. There is no explanation to how such a terrible phenomenon can occur. There is no scientific data explaining how this disorder started or how it affects so many people today, it is a mysterious disorder, that is very common across the globe (PubMed Health). But how is it inherited and what is the mutation. Research of
Achondroplasia consists of inheritance, causes, and treatment.
Achondroplasia is inherited by parents because it is getting passed down through generations, from one generation to the next. But it is not just a family trait, it is caused by a mutation in the FGFR3 gene. When this gene is defective, a person with this disorder can only grows to about 4ft tall their entire life, most people with this disorder stop growing at the age of 18. The FGFR3 gene stands for fibroblast
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growth factor receptor 3, a protein that converts cartilage to bone, which is very important in the early development in newborn babies. When they are born, their muscle tissue is extremely weak and fragile, which is why they need to be handled with such care. When the FGFR3 gene is mutated, the bone cartilage does not develop properly, and the child 's spine gets closed off at the bottom tip due to the mutation causing the spine and muscle tissue to mutate. All the people who have the normal FGFR3 gene are healthy and the FGFR3 mutation gene, have achondroplasia. The FGFR3 gene mutation can occur in one parent 's egg or sperm cell before the child is conceived. Other people with achondroplasia inherit the condition from one parent who has achondroplasia, even when the other parent does not
(Foundation, Human Growth). Mutations within a single gene is the cause of achondroplasia. It can come from a new mutation in the genes from averagesized, healthy parents. 9 out of 10 children born with achondroplasia have averagesized, healthy parents. A person with this mutated gene has achondroplasia and will have it their entire life. In 1994 Dr. John Wasmuth and his colleagues discovered that a mutation in the fibroblast growth factor receptor3 (FGFR3) gene on human chromosome 4 causes achondroplasia. To explain further, the person with this disorder, gets it when the
FGFR3 gene mutates, which causes mutations in bone cartilage and causes the entire skeletal structure to mutate. The cause of this mutation in the FGFR3 gene is not yet known. The main cause will not be known for some time, probably in the future. Until then, the cause of the gene mutation is unknown
(Foundation, Human Growth). Scientists wonder if there is any cure to this disease.
Many nonsurgical strategies people have thought about, consist of interfering with FGFR3 synthesis, how the gene stays stable, blocking its activation, stopping it from growing too much, inhibiting its tyrosine kinase activity, the development process, promoting its degradation, and antagonizing its downstream signals, manipulating the gene, in simpler terms, they are trying to find the
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main cause of the mutation, and they are trying to lock on t it and eliminate it (NYU Langone Medical
Center). Chemical inhibition of FGFR3 tyrosine kinase activity, antibody blockade of FGFR3 activation, and CNPmediated antagonism of FGFR3 downstream signals is what research has started with so far (National Library of Medicine). This process is discovering how they can have a positive effect on the gene growth. Here is an example. The disease known as Apert syndrome, is a classic and severe form of craniosynostosis, this is caused by the S252W mutation of FGFR2, which utilizes many of the same signaling pathways as the FGFR3 gene. FGFR3 and FGFR2 both have to do with body/bone development. Shukla et al [65, which is the chemical number code] utilized RNA interference to bring down the expression of the mutated FGFR2 allele. They generated a transgenic mouse strain that produced a shorthairpin RNA (shRNA, combined strains) that reduced expression of transcripts from the mutant FGFR2 allele.
This experiment determined what effect the gene mutation can have and what kind of effect an illness would have on it. When these mice were crossed with mice harboring a S252W FGFR2 allele and exhibiting features of Apert syndrome, the craniosynostosis phenotype was rescued. A similar approach targeted to the mutant FGFR3 allele in achondroplasia merits consideration, although delivery of an RNA interference vector to growth plate chondrocytes represents a challenge (Achondroplasia Research). These hypotheses, idea’s, and scientific notions will one day help discover what and how these disorders are created and how they can be stopped and annihilated. People with this disorder through a lot of different symptoms and health problems.
Approximately 2050% of all children with achondroplasia will experience some form of neurological impairment. This is caused by compression; created as they literally grow faster than their bones. The stunted bone growth at the base of the skull and the spine causes the spinal cord and brainstem to become compressed. This can lead to important nervous system structures such as, …show more content…
the
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brain stem, spinal cord, spinal nerve roots and cerebrospinal fluid (CSF) spaces, which can also be compressed. Eventually, this may lead to neurological deficits like Cervicomedullary Myelopathy,
Hydrocephalus, and Spinal Cord Myelopathy. Cervicomedullary Myelopathy is compression at the foramen magnum; the bony hole at the base of the skull where the brainstem and spinal cord exit the skull. This can cause a child’s brain stem to “kink”, which can cause a child to have symptoms like very brisk reflexes, numbness, weakness, difficulty walking, loss of bowel and bladder control, and sleep apnea; periods during sleep when a person stops breathing. Brainstem compression can result in death if it is left untreated. Hydrocephalus is when the spine gets extremely narrow near the base of the spine which prevents cerebrospinal fluid (CSF) from flowing around the brainstem or in and out of the skull, the CSF collects in ventricles. The resulting condition is hydrocephalus. In babies, the most common symptom of hydrocephalus is a quickly enlarging head circumference (Stöppler, Melissa Conrad). Other common symptoms are headaches, irritability, lethargy, and vomiting. A larger head is normal in achondroplastic children. Pediatricians can use a special head circumference growth chart to distinguish between normal achondroplastic growth and possible hydrocephalus. Spinal Cord Myelopathy is when the vertebrae of achondroplastic children does not grow enough to allow sufficient space for nerves entering and exiting the spinal cord to pass in and out of the bony spinal column. If only a single nerve root is compressed, symptoms of experiencing pain, numbness or weakness in a specific arm or leg. In more severe cases, the entire spinal cord can be compressed, causing weakness and numbness in the entire body below the spinal cord pinch as well as loss of bowel and bladder control (Achondroplasia
Homepage). There are different ways that Achondroplasia can be diagnosed. Achondroplasia can be diagnosed by characteristics, and radiographic findings in most affected individuals. Individuals in which there is diagnostic uncertainty or a typical findings, molecular genetic
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testing is used to detect a mutation in the FGFR3 gene. These testing detect mutations in 99% of affected individuals and is available in clinical laboratories only. There are many symptoms of
Achondroplasia, but the most severe ones need to be diagnosed before they do any permanent damage
(MedicineNet Diagnosis). For one, Hypochondroplasia is water flooding the brain, this and
Achondroplasia are related because one of the main symptoms of Achondroplasia is Hydrocephalus, which is when water floods the brain. It is diagnosed by the recognition of characteristic clinical and radiologic findings that are difficult to detect. The diagnosis is difficult to make in children under the age of three because as skeletal disproportion tends to be mild and many of the radiographic findings are very subtle during infancy. DNAbased testing is a fast way to discover this symptom. About 70% of affected individuals are heterozygous for a mutation in FGFR3. However, locus heterogeneity exists because mutations in other unidentified genes can result in similar, sometimes identical, phenotypes.
Another dangerous symptom is Thanatophoric Dysplasia, the disorder that causes Dwarfism and is extremely fatal at birth if not handled properly. TD is diagnosed, based on clinical examination and ultrasound examination and radiologic findings. FGFR3 is the only gene where the mutation is known to cause TD. 99% of mutations causing TD type I and more than 99% of mutations causing TD type II can be identified through molecular genetic testing of FGFR3. There are many symptoms of
Achondroplasia, but only a small amount are fatal (National Institute of Health). There are a lot of common symptoms for Achondroplasia, as well as uncommon ones.
The most common symptoms found in different patients are shortened arms and legs, with the upper arms and thighs more shortened than the forearms and lower legs, a large head size with prominent forehead and a flattened nasal bridge, crowded or misaligned teeth. A curved lower spine; a condition called lordosis (or swayback) which may lead to kyphosis, the development of a small hump
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near the shoulders that usually goes away after the child begins walking. Small vertebral canals which may lead to spinal cord compression in adolescence (Achondroplasia Johns Hopkins Orthopaedic
Surgery).
Occasionally children with achondroplasia may die suddenly during infancy or early childhood in their sleep due to compression of the upper end of the spinal cord, which interferes with breathing.
Bowed lower legs, flat feet that are short and broad, extra space between the middle and ring fingers
(Also called a trident hand), poor muscle tone and loose joints, frequent middle ear infections which may lead to hearing loss, abnormal intelligence, delayed developmental milestones such as walking
(which may occur between 18 to 24 months instead of around one year of age) (National Center for
Human Genome Research). There is a lot I learned and a lot more to be learned about this disorder.
The subtopics were on the causes of Achondroplasia, how it is inherited and what causes the gene mutation. It is inherited from parent to child, through family generations and the gene mutation is caused by mutation in the FGFR3 gene, a gene that has to do with cartilage development at an early stage of human growth. The symptoms, going over all the symptoms one with this disease might go through, common and uncommon symptoms. Most of the symptoms are painful, irritable and
very difficult to cure, almost impossible. But there are therapies that help these patients deal with the pain and the psychological defects one with this disorder might have. Curable treatments, research stating if there is any known cure or treatment that helps this disorder. There is NO cure for this disease, and there is no treatment that can cure the symptoms. However, there are a lot of different therapies that help people with Achondroplasia symptoms slowly recover from the pain and trauma they suffer through.
People with Achondroplasia inherit this disease, or their FGFR3 gene is mutated. There are a lot of different symptoms that come from this disease, and there is no cure but there are a lot of treatments that help with pain. Overall, this is a very interesting topic to research, there was a lot of research online,
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in books and all my sources were interesting and credible. This is a very interesting topic, in conclusion,
Achondroplasia is a rare and sometimes fatal disease, passed down through generations and families and involves intense gene mutation.
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Works Cited
"Achondroplasia." Achondroplasia. U.S. National Library of Medicine, 13 Nov. 2011. Web. 12
Feb. 2013.
"Achondroplasia." Genetics Home Reference. Ed. Wendling D. Bethesda. National Library of
Medicine, 3 May 2007. Web. 12 Feb. 2013.
Hopkins, Johns. "Achondroplasia Johns Hopkins Orthopaedic Surgery." Achondroplasia Johns
Hopkins Orthopaedic Surgery. Johns Hopkins Department of Orthopaedic Surgery, 9 Apr.
2009. Web. 12 Feb. 2013.
Kassir, Kari. "Achondroplasia." NYU Langone Medical Center. Kari Kassir, MD, 5 Sept. 2012.
Web. 12 Feb. 2013.
"Learning About Achondroplasia." Learning About Achondroplasia. National Institute of Health,
23 Jan. 2012. Web. 12 Feb. 2013.
Stöppler, Melissa Conrad. "Achondroplasia Symptoms, Causes, Treatment How Is
Achondroplasia Diagnosed? on MedicineNet." MedicineNet. David Perlstein, 6 Feb. 2012. Web.
14 Feb. 2013.
Foundation, Human Growth. "Achondroplasia." National Center for Human Genome Research.
Human Growth Foundation, 2 Mar. 2000. Web.
Mick St John
April 8, 2013
Achondroplasia (Dwarfism)
One in every 15,000 to 40,000 people have Achondroplasia. This means that over 466 million people on the planet have Achondroplasia. Achondroplasia is a genetic disorder that is a part of a group of disorders called chondrodystrophies or osteochondrodysplasias. Achondroplasia literally means
"without cartilage formation". Cartilage is a strong and flexible tissue that makes up most of the skeleton during a child’s early development, without it, the child has no chance of growing properly (Genetics
Home Reference). This disorder is passed down through family generations, it is a dominant trait that one or both parents can carry and if one parent has it, in almost every case, the child inherits this …show more content…
disorder. If one parent carries the gene mutation, the child has a 50% chance of inheriting it. If both parents carry it, then the child has a 75% chance of being born with this disorder. In some rare cases, neither of the parents carry the disorder, but the child is still born with Achondroplasia. There is no explanation to how such a terrible phenomenon can occur. There is no scientific data explaining how this disorder started or how it affects so many people today, it is a mysterious disorder, that is very common across the globe (PubMed Health). But how is it inherited and what is the mutation. Research of
Achondroplasia consists of inheritance, causes, and treatment.
Achondroplasia is inherited by parents because it is getting passed down through generations, from one generation to the next. But it is not just a family trait, it is caused by a mutation in the FGFR3 gene. When this gene is defective, a person with this disorder can only grows to about 4ft tall their entire life, most people with this disorder stop growing at the age of 18. The FGFR3 gene stands for fibroblast
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growth factor receptor 3, a protein that converts cartilage to bone, which is very important in the early development in newborn babies. When they are born, their muscle tissue is extremely weak and fragile, which is why they need to be handled with such care. When the FGFR3 gene is mutated, the bone cartilage does not develop properly, and the child 's spine gets closed off at the bottom tip due to the mutation causing the spine and muscle tissue to mutate. All the people who have the normal FGFR3 gene are healthy and the FGFR3 mutation gene, have achondroplasia. The FGFR3 gene mutation can occur in one parent 's egg or sperm cell before the child is conceived. Other people with achondroplasia inherit the condition from one parent who has achondroplasia, even when the other parent does not
(Foundation, Human Growth). Mutations within a single gene is the cause of achondroplasia. It can come from a new mutation in the genes from averagesized, healthy parents. 9 out of 10 children born with achondroplasia have averagesized, healthy parents. A person with this mutated gene has achondroplasia and will have it their entire life. In 1994 Dr. John Wasmuth and his colleagues discovered that a mutation in the fibroblast growth factor receptor3 (FGFR3) gene on human chromosome 4 causes achondroplasia. To explain further, the person with this disorder, gets it when the
FGFR3 gene mutates, which causes mutations in bone cartilage and causes the entire skeletal structure to mutate. The cause of this mutation in the FGFR3 gene is not yet known. The main cause will not be known for some time, probably in the future. Until then, the cause of the gene mutation is unknown
(Foundation, Human Growth). Scientists wonder if there is any cure to this disease.
Many nonsurgical strategies people have thought about, consist of interfering with FGFR3 synthesis, how the gene stays stable, blocking its activation, stopping it from growing too much, inhibiting its tyrosine kinase activity, the development process, promoting its degradation, and antagonizing its downstream signals, manipulating the gene, in simpler terms, they are trying to find the
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main cause of the mutation, and they are trying to lock on t it and eliminate it (NYU Langone Medical
Center). Chemical inhibition of FGFR3 tyrosine kinase activity, antibody blockade of FGFR3 activation, and CNPmediated antagonism of FGFR3 downstream signals is what research has started with so far (National Library of Medicine). This process is discovering how they can have a positive effect on the gene growth. Here is an example. The disease known as Apert syndrome, is a classic and severe form of craniosynostosis, this is caused by the S252W mutation of FGFR2, which utilizes many of the same signaling pathways as the FGFR3 gene. FGFR3 and FGFR2 both have to do with body/bone development. Shukla et al [65, which is the chemical number code] utilized RNA interference to bring down the expression of the mutated FGFR2 allele. They generated a transgenic mouse strain that produced a shorthairpin RNA (shRNA, combined strains) that reduced expression of transcripts from the mutant FGFR2 allele.
This experiment determined what effect the gene mutation can have and what kind of effect an illness would have on it. When these mice were crossed with mice harboring a S252W FGFR2 allele and exhibiting features of Apert syndrome, the craniosynostosis phenotype was rescued. A similar approach targeted to the mutant FGFR3 allele in achondroplasia merits consideration, although delivery of an RNA interference vector to growth plate chondrocytes represents a challenge (Achondroplasia Research). These hypotheses, idea’s, and scientific notions will one day help discover what and how these disorders are created and how they can be stopped and annihilated. People with this disorder through a lot of different symptoms and health problems.
Approximately 2050% of all children with achondroplasia will experience some form of neurological impairment. This is caused by compression; created as they literally grow faster than their bones. The stunted bone growth at the base of the skull and the spine causes the spinal cord and brainstem to become compressed. This can lead to important nervous system structures such as, …show more content…
the
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brain stem, spinal cord, spinal nerve roots and cerebrospinal fluid (CSF) spaces, which can also be compressed. Eventually, this may lead to neurological deficits like Cervicomedullary Myelopathy,
Hydrocephalus, and Spinal Cord Myelopathy. Cervicomedullary Myelopathy is compression at the foramen magnum; the bony hole at the base of the skull where the brainstem and spinal cord exit the skull. This can cause a child’s brain stem to “kink”, which can cause a child to have symptoms like very brisk reflexes, numbness, weakness, difficulty walking, loss of bowel and bladder control, and sleep apnea; periods during sleep when a person stops breathing. Brainstem compression can result in death if it is left untreated. Hydrocephalus is when the spine gets extremely narrow near the base of the spine which prevents cerebrospinal fluid (CSF) from flowing around the brainstem or in and out of the skull, the CSF collects in ventricles. The resulting condition is hydrocephalus. In babies, the most common symptom of hydrocephalus is a quickly enlarging head circumference (Stöppler, Melissa Conrad). Other common symptoms are headaches, irritability, lethargy, and vomiting. A larger head is normal in achondroplastic children. Pediatricians can use a special head circumference growth chart to distinguish between normal achondroplastic growth and possible hydrocephalus. Spinal Cord Myelopathy is when the vertebrae of achondroplastic children does not grow enough to allow sufficient space for nerves entering and exiting the spinal cord to pass in and out of the bony spinal column. If only a single nerve root is compressed, symptoms of experiencing pain, numbness or weakness in a specific arm or leg. In more severe cases, the entire spinal cord can be compressed, causing weakness and numbness in the entire body below the spinal cord pinch as well as loss of bowel and bladder control (Achondroplasia
Homepage). There are different ways that Achondroplasia can be diagnosed. Achondroplasia can be diagnosed by characteristics, and radiographic findings in most affected individuals. Individuals in which there is diagnostic uncertainty or a typical findings, molecular genetic
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testing is used to detect a mutation in the FGFR3 gene. These testing detect mutations in 99% of affected individuals and is available in clinical laboratories only. There are many symptoms of
Achondroplasia, but the most severe ones need to be diagnosed before they do any permanent damage
(MedicineNet Diagnosis). For one, Hypochondroplasia is water flooding the brain, this and
Achondroplasia are related because one of the main symptoms of Achondroplasia is Hydrocephalus, which is when water floods the brain. It is diagnosed by the recognition of characteristic clinical and radiologic findings that are difficult to detect. The diagnosis is difficult to make in children under the age of three because as skeletal disproportion tends to be mild and many of the radiographic findings are very subtle during infancy. DNAbased testing is a fast way to discover this symptom. About 70% of affected individuals are heterozygous for a mutation in FGFR3. However, locus heterogeneity exists because mutations in other unidentified genes can result in similar, sometimes identical, phenotypes.
Another dangerous symptom is Thanatophoric Dysplasia, the disorder that causes Dwarfism and is extremely fatal at birth if not handled properly. TD is diagnosed, based on clinical examination and ultrasound examination and radiologic findings. FGFR3 is the only gene where the mutation is known to cause TD. 99% of mutations causing TD type I and more than 99% of mutations causing TD type II can be identified through molecular genetic testing of FGFR3. There are many symptoms of
Achondroplasia, but only a small amount are fatal (National Institute of Health). There are a lot of common symptoms for Achondroplasia, as well as uncommon ones.
The most common symptoms found in different patients are shortened arms and legs, with the upper arms and thighs more shortened than the forearms and lower legs, a large head size with prominent forehead and a flattened nasal bridge, crowded or misaligned teeth. A curved lower spine; a condition called lordosis (or swayback) which may lead to kyphosis, the development of a small hump
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near the shoulders that usually goes away after the child begins walking. Small vertebral canals which may lead to spinal cord compression in adolescence (Achondroplasia Johns Hopkins Orthopaedic
Surgery).
Occasionally children with achondroplasia may die suddenly during infancy or early childhood in their sleep due to compression of the upper end of the spinal cord, which interferes with breathing.
Bowed lower legs, flat feet that are short and broad, extra space between the middle and ring fingers
(Also called a trident hand), poor muscle tone and loose joints, frequent middle ear infections which may lead to hearing loss, abnormal intelligence, delayed developmental milestones such as walking
(which may occur between 18 to 24 months instead of around one year of age) (National Center for
Human Genome Research). There is a lot I learned and a lot more to be learned about this disorder.
The subtopics were on the causes of Achondroplasia, how it is inherited and what causes the gene mutation. It is inherited from parent to child, through family generations and the gene mutation is caused by mutation in the FGFR3 gene, a gene that has to do with cartilage development at an early stage of human growth. The symptoms, going over all the symptoms one with this disease might go through, common and uncommon symptoms. Most of the symptoms are painful, irritable and
very difficult to cure, almost impossible. But there are therapies that help these patients deal with the pain and the psychological defects one with this disorder might have. Curable treatments, research stating if there is any known cure or treatment that helps this disorder. There is NO cure for this disease, and there is no treatment that can cure the symptoms. However, there are a lot of different therapies that help people with Achondroplasia symptoms slowly recover from the pain and trauma they suffer through.
People with Achondroplasia inherit this disease, or their FGFR3 gene is mutated. There are a lot of different symptoms that come from this disease, and there is no cure but there are a lot of treatments that help with pain. Overall, this is a very interesting topic to research, there was a lot of research online,
St John 7
in books and all my sources were interesting and credible. This is a very interesting topic, in conclusion,
Achondroplasia is a rare and sometimes fatal disease, passed down through generations and families and involves intense gene mutation.
St John 8
Works Cited
"Achondroplasia." Achondroplasia. U.S. National Library of Medicine, 13 Nov. 2011. Web. 12
Feb. 2013.
"Achondroplasia." Genetics Home Reference. Ed. Wendling D. Bethesda. National Library of
Medicine, 3 May 2007. Web. 12 Feb. 2013.
Hopkins, Johns. "Achondroplasia Johns Hopkins Orthopaedic Surgery." Achondroplasia Johns
Hopkins Orthopaedic Surgery. Johns Hopkins Department of Orthopaedic Surgery, 9 Apr.
2009. Web. 12 Feb. 2013.
Kassir, Kari. "Achondroplasia." NYU Langone Medical Center. Kari Kassir, MD, 5 Sept. 2012.
Web. 12 Feb. 2013.
"Learning About Achondroplasia." Learning About Achondroplasia. National Institute of Health,
23 Jan. 2012. Web. 12 Feb. 2013.
Stöppler, Melissa Conrad. "Achondroplasia Symptoms, Causes, Treatment How Is
Achondroplasia Diagnosed? on MedicineNet." MedicineNet. David Perlstein, 6 Feb. 2012. Web.
14 Feb. 2013.
Foundation, Human Growth. "Achondroplasia." National Center for Human Genome Research.
Human Growth Foundation, 2 Mar. 2000. Web.