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.
Coffin-Lowry syndrome is a condition that affects many parts of the body. The signs and symptoms are usually more severe in males than in females, although the features of this disorder range from very mild to severe in affected women.
Males with Coffin-Lowry syndrome typically have severe to profound intellectual disability and delayed development. Affected women may be cognitively normal, or they may have intellectual disability ranging from mild to profound. Beginning in childhood or adolescence, some people with this condition experience brief episodes of collapse when excited or startled by a loud noise. These attacks are called stimulus-induced drop episodes (SIDEs).
Most affected males and some affected females have distinctive facial features including a prominent forehead, widely spaced and downward-slanting eyes, a short nose with a wide tip, and a wide mouth with full lips. These features become more pronounced with age. Soft hands with short, tapered fingers are also characteristic of Coffin-Lowry syndrome. Additional features of this condition include short stature, an unusually small head (microcephaly), progressive abnormal curvature of the spine (kyphoscoliosis), and other skeletal abnormalities.
The incidence of this condition is uncertain, but researchers estimate that the disorder affects 1 in 40,000 to 50,000 people.
Mutations in the RPS6KA3 gene cause Coffin-Lowry syndrome. This gene provides instructions for making a protein that is involved in signalling 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 signalling pathways that are required for learning, the formation of long-term memories, and the survival of nerve cells. Gene mutations result in the production of little or no RPS6KA3 protein, but it is unclear how a lack of this protein causes the signs and symptoms of Coffin-Lowry syndrome.
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 mutated 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 in each cell is sufficient to cause the condition. In most cases, males (who have one X chromosome in each cell) experience more severe signs and symptoms of the disorder than females (who have two X chromosomes in each cell). A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
Between 70 percent and 80 percent of people with Coffin-Lowry syndrome have no history of the condition in their families. These cases are caused by new mutations in the RPS6KA3 gene. The remaining 20 percent to 30 percent of affected individuals have other family members with Coffin-Lowry syndrome.
Resources and Support
Coffin-Lowry is such a rare disease, that very few UK institutions/support groups are available or have any resources. Much of what we describe above is taken from information supplied by the US National Library of Medicine: Genetics Home Reference which has detailed information on the condition. The National Organisation for Rare Diseases (NORD) , also US based, is another source of information. There is also the inevitable Wikipedia page. There is a support organisation, The Coffin Lowry Syndrome Foundation which has a mine of information from parents in the US who have children with CLS. Unfortunately, whilst there are affiliated organisations in France, Germany, Portugal and Spain, the UK doesn’t yet have such an organisation dedicated to CLS.
There is however, Contact an organisation for UK families of disabled children who can offer some support. In addition, Metabolic Support UK have a page on James, a young boy with CLS. More information on James’s story can be found at the Same But Different support group.