What symptoms does Noonan Syndrome present?
Also known as Leopard Syndrome, Noonan syndrome (NS) is a developmental disease that is characterized by short stature, unusual facial characteristics, heart defects, skeletal malformations and numerous other physical defects. However, these physical characteristics can vary significantly between individuals due to the various molecular causes of NS (1).
What is the molecular basis for Noonan Syndrome?
The physiological features of NS are caused by one or many mutations of proteins that are employed in the RAS/MAPK cell signaling pathway. For NS, this signaling pathway is important because it controls formation of numerous tissues during a child's development. Additionally, this signaling pathway is well-known due to its role in the development of many types of cancer and Hodgkin disease. PTPN11 is the most commonly mutated gene within this pathway (50% of NS cases) others such as SOS1, KRAS, and RAF1 account for about 30% of cases. The mutations in these genes alter the translated protein so that they cannot be regulated and are constantly active. But what about the remaining 20 percent? A fifth of NS cases are caused by unknown mutations and more is being learned as scientists discover novel mutations (1).
How do people get Noonan Syndrome?
As a genetically inherited disease, it is impossible to contract NS. The genetic traits for the disease are transferred in a autosomally dominant pattern which means if a child inherits one of the mutations from his parents, it will be expressed and he/she will have NS. This means that children with a parent afflicted with Noonan Syndrome have a 50% chance of inheriting the disease. However, there are uncommon special cases where a mutation arises in the womb, resulting in a child to be born with NS without any parents having the disease (1).
How is Noonan Syndrome diagnosed?
While it is possible to diagnose NS based on an individuals physical characteristics, it is also possible to genetically test for common mutations associated with the disease via DNA sequencing.
Is it possible to treatment Noonan Syndrome?
Noonan syndrome is treated at the symptoms level rather than at the root cause of the disease due to its complexity at a molecular level. This includes numerous surgical procedures for associated heart defects, HGH (human growth hormone) for inducing the normally stunted growth rate, speech therapy, and most affected individuals require a form of special education. While there are many drugs used to inhibit proteins in the RAS/MAPK pathway for treating cancer, these types of drugs will interfere with a child's development and are not used to treat NS. However, current research is underway looking for drugs that will mitigate the effect of aberrant RAS/MAPK proteins without removing their function altogether (2).
References:
1) "Noonan Syndrome." Genetics Home Reference. NIH, Mar. 2011. Web. 27 Mar. 2015.
2) "Noonan Syndrome - Treatment ." Noonan Syndrome. NHS, 10 Mar. 2013. Web. 27 Mar. 2015.
Also known as Leopard Syndrome, Noonan syndrome (NS) is a developmental disease that is characterized by short stature, unusual facial characteristics, heart defects, skeletal malformations and numerous other physical defects. However, these physical characteristics can vary significantly between individuals due to the various molecular causes of NS (1).
What is the molecular basis for Noonan Syndrome?
The physiological features of NS are caused by one or many mutations of proteins that are employed in the RAS/MAPK cell signaling pathway. For NS, this signaling pathway is important because it controls formation of numerous tissues during a child's development. Additionally, this signaling pathway is well-known due to its role in the development of many types of cancer and Hodgkin disease. PTPN11 is the most commonly mutated gene within this pathway (50% of NS cases) others such as SOS1, KRAS, and RAF1 account for about 30% of cases. The mutations in these genes alter the translated protein so that they cannot be regulated and are constantly active. But what about the remaining 20 percent? A fifth of NS cases are caused by unknown mutations and more is being learned as scientists discover novel mutations (1).
How do people get Noonan Syndrome?
As a genetically inherited disease, it is impossible to contract NS. The genetic traits for the disease are transferred in a autosomally dominant pattern which means if a child inherits one of the mutations from his parents, it will be expressed and he/she will have NS. This means that children with a parent afflicted with Noonan Syndrome have a 50% chance of inheriting the disease. However, there are uncommon special cases where a mutation arises in the womb, resulting in a child to be born with NS without any parents having the disease (1).
How is Noonan Syndrome diagnosed?
While it is possible to diagnose NS based on an individuals physical characteristics, it is also possible to genetically test for common mutations associated with the disease via DNA sequencing.
Is it possible to treatment Noonan Syndrome?
Noonan syndrome is treated at the symptoms level rather than at the root cause of the disease due to its complexity at a molecular level. This includes numerous surgical procedures for associated heart defects, HGH (human growth hormone) for inducing the normally stunted growth rate, speech therapy, and most affected individuals require a form of special education. While there are many drugs used to inhibit proteins in the RAS/MAPK pathway for treating cancer, these types of drugs will interfere with a child's development and are not used to treat NS. However, current research is underway looking for drugs that will mitigate the effect of aberrant RAS/MAPK proteins without removing their function altogether (2).
References:
1) "Noonan Syndrome." Genetics Home Reference. NIH, Mar. 2011. Web. 27 Mar. 2015.
2) "Noonan Syndrome - Treatment ." Noonan Syndrome. NHS, 10 Mar. 2013. Web. 27 Mar. 2015.