Coffin–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.
Coffin–Lowry syndrome is a severe intellectual disability associated with abnormalities of:
- In utero growth is normal but post natal growth is retarded. 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.
- Vision and audition
- 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. 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.
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.
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.
X-ray and neuroimaging studies may be helpful in confirming a diagnosis of Coffin–Lowry syndrome. Decreased ribosomal S6 kinase activity in cultured fibroblast or transformed lymphoblast cells from a male indicates Coffin–Lowry syndrome. Studies of enzyme activity can not be used to diagnose an affected female.
Molecular genetic testing on a blood specimen or cells from a cheek swab is available to identify mutations in the RSK2 gene. This testing can be used to confirm but not rule out the diagnosis of Coffin–Lowry syndrome because not all affected individuals have a detectable mutation.
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There is no cure and no standard course of treatment for Coffin–Lowry syndrome. Treatment is symptomatic and supportive, and may include occupational, physical and speech therapy and educational services.
Coffin–Lowry was first described by Grange S. Coffin (b. 1923) in 1966 and independently by Robert Brian Lowry (b. 1932) in 1971. Dr. Temtamy showed that the cases represented a single syndrome in 1975.
The Coffin–Lowry Syndrome Foundation acts as a clearinghouse for information on Coffin–Lowry syndrome and hosts a forum for affected families. The family matching program facilitates community building and resource sharing for recent diagnoses.
- 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.
- synd/3425 at Who Named It?
- "Coffin Lowry Syndrome - NORD (National Organization for Rare Disorders)". RareDiseases.org. Retrieved February 2, 2017.
- Coffin GS, Siris E, Wegienka LC (1966). "Mental retardation with osteocartilaginous anomalies". Am. J. Dis. Child. 112 (3): 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.
- "Home". www.clsf.info.
- "Coffin–Lowry Syndrome Foundation". National Institute of Neurological Disorders and Stroke. Retrieved 29 February 2016.
This article incorporates public domain text from The U.S. National Library of Medicine and the National Institute of Neurological Disorders and Stroke.
- GeneReviews/UW/NIH entry on Coffin–Lowry syndrome