Some science behind the scenes
Coffin–Lowry syndrome is a genetic disorder that is X-linked dominant and caused by mutations in the RPS6KA3 gene. Some people with the features of Coffin–Lowry syndrome do not have identified mutations in the RPS6KA3 gene. In these cases, the cause of the condition is unknown.
A majority of boys with Coffin–Lowry syndrome have no history of the condition in their families. These cases are caused by new mutations in the RPS6KA3 gene (de novo mutations). A new mutation means that neither parent has the altered gene, but the affected individual could pass it on to his children.
It was described by Grange S. Coffin (b. 1923) in 1966 and Robert Brian Lowry (b. 1932) in 1971.
It results in severe mental problems sometimes associated with abnormalities of growth. It can produce:
- severe mental retardation
- retarded post natal growth, even though in utero growth was normal. Patients are sometimes microcephalic.
- cardiac abnormalities affect 15% of the patients.
- progressive kyphoscoliosis affects 1 in 2 patients. Micrognathia is also associated with this syndrome.
- patients may also have an underdeveloped upper jaw bone, abnormally prominent brows, or widely spaced eyes.
- Auditory abnormalities are frequent and often present. Vision abnormalities are not often present.
The syndrome is caused by mutations in the RPS6KA3 gene. This gene is located on the short arm of the X chromosome (Xp22.2).
The RPS6KA3 gene makes a protein that is involved with signaling within cells. Researchers believe that this protein helps control the activity of other genes and plays an important role in the brain. The protein is involved in cell signaling pathways that are required for learning, the formation of long-term memories, and the survival of nerve cells. The protein RSK2 which is encoded by the RPS6KA3 gene is a kinase which phosphorylates some substrates like CREB and histone H3. RSK2 is involved at the distal end of the Ras/MAPK signaling pathway. Mutations in the RPS6KA3 disturb the function of the protein, but it is unclear how a lack of this protein causes the signs and symptoms of Coffin–Lowry syndrome. At this time more than 120 mutations have been found.
This condition is inherited in an X-linked dominant pattern. A condition is considered X-linked if the gene that causes the disorder is located on the X chromosome (one of the two sex chromosomes). The inheritance is dominant if one copy of the altered gene is sufficient to cause the condition. In most cases, males experience more severe symptoms of the disorder than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
Although the cause of the various manifestations is a mutation in the gene, this is not in fact the actual cause, as we need to know what caused the mutation.
As the problem here is a generic one for all inherited diseases caused by mutation it is discussed in the section Inherited illness, please follow the link.
- Coffin GS, Siris E, Wegienka LC (1966). "Mental retardation with osteocartilaginous anomalies". Am. J. Dis. Child. 112: 205–213. doi:10.1001/archpedi.1966.02090120073006.
- Lowry B, Miller JR, Fraser FC (June 1971). "A new dominant gene mental retardation syndrome. Association with small stature, tapering fingers, characteristic facies, and possible hydrocephalus". Am. J. Dis. Child. 121 (6): 496–500. doi:10.1001/archpedi.1971.02100170078009. PMID 5581017.
- Delaunoy JP, Dubos A, Marques Pereira P, Hanauer A (August 2006). "Identification of novel mutations in the RSK2 gene (RPS6KA3) in patients with Coffin–Lowry syndrome". Clin. Genet. 70 (2): 161–6. doi:10.1111/j.1399-0004.2006.00660.x. PMID 16879200.