Specialty medical genetics ICD-9-CM 759.89 DiseasesDB 2934 | ICD-10 Q87.8 OMIM 303600 MeSH D038921 | |
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.
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Symptoms
Coffin–Lowry syndrome is a severe mental retardation associated with abnormalities of:
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 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.
Diagnosis
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.
Prognosis
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.
History
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.
Community resources
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.