A syndrome is a set of specific medical signs, characteristics and symptoms. Coffin-Lowry syndrome was originally described independently by Dr. Coffin and associates in 1966, and again by Dr. Lowry and associates in 1971. In 1975, Dr. Temtamy showed that the cases represented a single syndrome. The estimated prevalence at birth is 1:45,000 (Orpha.net, Listing ORPHA192). CLS has been reported in various ethnic groups (Young, 1988). About 65% of cases of Coffin-Lowry syndrome are caused by changes (mutations) in the RPS6KA3 gene located at Xp22.2. This gene encodes RSK2, a growth-factor-regulated protein kinase. The gene was identified in 1996. The gene is located on the X-chromosome; how the defective gene produces the signs and symptoms is still not entirely clear. There are still many cases of CLS where the exact cause is unknown. About 70-80% of individuals with CLS have no family history, whereas 20-30% have more than one additional affected family member. In the case of multiple affected family members, the genetic defect may be inherited from a female carrier who exhibits at least some of the characteristics of CLS herself; there is also evidence to support gonadal mosaicism in some families where the genetic defect only exists in the mother's eggs and she is not otherwise affected.
CLS is an X-linked dominant disorder. Girls have two X chromosomes. Boys have one X chromosome and one Y chromosome. If the gene has a change (mutation) on one of the X chromosomes, the child will have CLS. Since males only have one X chromosome, they have more severe symptoms. Since females have two X-chromosomes, they have one normal X chromosome and one abnormal X chromosome. Because they still have one X chromosome that is normal, they often have milder symptoms.
It has been suggested that not all individuals with a clinical diagnosis thought to be consistent with CLS have mutations in the RSK2 gene [Delaunoy et al 2001; Zeniou, Pannetier et all 2002]. However it is not clear whether this means that other as yet unidentified conditions are being categorized with CLS or not.
There have been reports of mild expression of CLS in males who had the RPS6KA3 mutation [Manouvrier-Hanu et all 1999] but little is known about this form of CLS at this time.
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.