Coffinâ€"Lowry syndrome is a genetic disorder that is X-linked dominant and which causes severe mental problems sometimes associated with abnormalities of growth, cardiac abnormalities, kyphoscoliosis, as well as auditory and visual abnormalities.
History
It was characterized by Grange S. Coffin (b. 1923) in 1966 and Robert Brian Lowry (b. 1932) in 1971.
Coffinâ€"Lowry syndrome was independently described by Dr. Coffin and his associates in 1966 and later described by Dr. Lowry and associates in 1971. Dr. Temtamy showed that the cases represented a single syndrome in 1975.
Causes
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 Coffinâ€"Lowry syndrome. At this time more than 120 mutations have been found. Some people with the features of Coffinâ€"Lowry syndrome do not have identified mutations in the RPS6KA3 gene. In these cases, the cause of the condition is unknown.
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.
A majority of boys with Coffinâ€"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.
Prognosis
There is no cure and no standard course of treatment for Coffinâ€"Lowry syndrome. Treatment is symptomatic and supportive, and may include physical and speech therapy and educational services.
Symptoms
Coffinâ€"Lowry syndrome is a severe mental retardation associated with abnormalities of:
- Growth
- In utero growth is normal but post natal growth is retarded. Patients are sometimes microcephalic.
- Cardio-vascular
- Cardiac abnormalities affect 15% of the patients.
- Skeleton
- 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.
- Vision and audition
- Auditory abnormalities are frequent and often present. Vision abnormalities are not often present.
References
This article incorporates public domain text from The U.S. National Library of Medicine and the National Institute of Neurological Disorders and Stroke.
External links
- GeneReviews/UW/NIH entry on Coffinâ€"Lowry syndrome
- Coffinâ€"Lowry Syndrome Foundation
- http://ghr.nlm.nih.gov/condition/coffin-lowry-syndrome
- http://www.wrongdiagnosis.com/c/coffin_lowry_syndrome/symptoms.htm