Frequently Asked Questions
Q: What is Coffin-Lowry syndrome?
A: 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 there is a great deal of variability in expression, especially in females. 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.
Q: How common is it?
The exact incidence is not known, but researchers estimate the prevalence at one in every 40-50,000 births.
Q: What genes are related to CLS?
Coffin-Lowry syndrome is caused by mutations in the RPS6KA3 gene. More than 125 mutations in the RPS6KA3 gene have been identified in people with Coffin-Lowry syndrome. All of these mutations severely reduce or eliminate the activity of the RPS6KA3 protein. Some mutations insert or delete genetic material in the gene or change how the gene's instructions are use to build the protein. Other mutations change single protein building blocks (amino acids) in the RPS6KA3 protein. This gene encodes RSK2, a growth-factor-regulated protein kinase. Some people with the features of CLS do not have the identified mutations in this gene. In these cases, the cause of the condition is unknown.
Q: Is CLS progressive?
A: Some aspects of the syndrome are progressive. Facial coarsening and skeletal involvement become more pronounced with age. Some motor and coordination neurological problems do not express themselves until later in childhood and may result in decreased mobility. Bone degeneration may occur starting in the late teen years which can lead to a higher incidence of broken bones. This is especially problematic for those who also have drop episodes as they are prone to spine and neck injuries from the repeated falls. Depression or behavior problems may develop. Life expectancy may be reduced in individuals who have severe cardiac problems, respiratory complications, or severe progressive kyphoscoliosis.
Q: Is there a test for CLS?
A: Molecular genetic testing of RPS6KA3, can be used to confirm, but not to rule out, the diagnosis of CLS. Sequence analysis identifies mutations in about 35%-40% of probands. Dozens of mutations have been identified that can cause CLS characteristics. This makes a positive diagnosis using genetic testing very difficult. Professionals trained in genetic disorders and birth defects often can make the diagnosis after performing a physical exam and observing the child's behavior.
Often a diagnosis comes after a developmental evaluation when a child appears to be delayed in reaching several developmental milestones. Parents should be prepared for the likelihood that even though a clinical diagnosis is made, they may not get a confirming positive genetic diagnosis.