Coffin-Lowry Syndrome
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Coffin-Lowry Syndrome
A developmental disability is “a severe, permanent, physical or psychological impairment originating before the age of 22 and causing severe functional disruptions (handicaps) in the persons life” (Graziano, 2001). When assessing the etiology, pathology, impairments and disabilities of Coffin-Lowry Syndrome (CLS) it is evident that CLS is a developmental disability. CLS is a severe form of X-linked mental retardation with marked phenotypic variability that interferes with the affected individuals social, psychological and everyday functioning.
The agents that cause the structural or biological changes in the individual with CLS are referred to as the etiology of the developmental disability. In order to assess the etiology of CLS it is important to understand what CLS is. CLS was originally described independently by Dr. Coffin and associates in 1966 and again by Dr. Lowry and associates in 1971. Dr. Temtamy, in 1975, indicated that Coffin-Lowry cases represented a single rare syndrome. It is caused by a mutation in the kinase Rsk-2 protein, which is a growth factor regulator. This gene was identified in 1996 and is located on the short arm of the X-chromosome (Coffin-Lowry Foundation, 2003). CLS is thought to be in the region from Xp22.1-p22.2. Several other disease genes are also located in this area. Two diseases are juvenile retinoschisis and X-linked hypophosphatemic rickets (Patterson, 2000).
The inheritance of CLS is X-linked. A woman who has CLS has a 50/50 chance of having a child with CLS, depending on which of her X-chromosomes are inherited by the child. CLS is also caused by a spontaneous mutation in which there is no family history. In this situation, the risk of having another affected child is very low. There are no recorded cases of an affected male producing offspring, so the ability of CLS males to father affected children is not known (Coffin-Lowry Foundation, 2003).
There is no 100% conclusive test for CLS, however researchers are getting closer. Every individual who has the Rsk-2 defect will have CLS, but there are individuals who do not have the Rsk-2 defect that still have CLS characteristics. There are over 90 separate mutations that have been associated with causing CLS characteristics. This makes diagnosis using genetic testing very difficult. In observing the childs behavior and performing a physical exam professionals trained in genetic disorders and birth defects often can conclude a diagnosis. Diagnosing CLS in infancy can be difficult because the physical characteristics are usually mild, more so in females and, can be confused with other syndromes. Often a diagnosis comes after a developmental evaluation when a child expresses a delay in reaching several developmental milestones. Early diagnosis of CLS is essential for proper management (Coffin-Lowry Foundation, 2003). CLS has been reported in families of European, Asian and African origin. It is more common and prominent in males. The incidence of CLS is unknown but, lies approximately in the range of 1 in 50-100,000 males (Touraine, Zaeniou & Hanauer, 2002).
The structural or biological changes that occur in the individual with CLS are associated with the Pathology of the disability. Unfortunately the nature of the anatomical and physiological defects in CLS patients in relation to Rsk-2 mutations is still poorly understood. However, the fact that cognitive impairments are a prominent feature of patients with CLS is an indicator of the important role of Rsks in development and function of the central nervous system. No pathological abnormalities have been reported suggesting that Rsk-2 is not required for major aspects of brain development. It is also unclear how mutations in Rsk-2 give rise to skeletal defects in effected individuals with CLS. The mechanism by which Rsk-2 contributes to proper skeleton formation is unknown (Touraine, Zeniou & Hanauer, 2002).
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