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Cognitive function in Coffin-Lowry syndrome
R J Simensen1, F Abidi, J S Collins
1J. C. Self Research Institute of Human Genetics, Greenwood Genetic Center, SC 29646, USA. simensen@ggc.org
Clinical Genetics
|May 29, 2002
Summary
Coffin-Lowry syndrome (CLS), caused by RSK2 gene mutations, significantly impacts cognitive function. Affected males and carrier females exhibit intellectual deficits, with carriers showing milder effects than affected individuals.
Area of Science:
- Genetics
- Neuroscience
- Developmental Biology
Background:
- Coffin-Lowry syndrome (CLS) is an X-linked disorder characterized by intellectual disability, distinct facial and hand features, hypotonia, and skeletal abnormalities.
- Mutations in the RSK2 gene (Ribosomal S6 Kinase 2) on chromosome Xp22.2 are the known cause of CLS.
- While clinical features are documented, the cognitive impact on affected males and carrier females remains under-researched.
Purpose of the Study:
- To investigate the cognitive deficits in individuals with Coffin-Lowry syndrome, specifically focusing on affected males and carrier females.
- To analyze the cognitive performance hierarchy across normal, carrier, and affected individuals within families.
- To explore the relationship between X-inactivation patterns and cognitive function in carrier females.
Main Methods:
- Study involved two African-American families with a shared RSK2 missense mutation (C340T).
- Participants included affected males (6), carrier females (7), normal males (3), and normal females (3).
- Cognitive function was assessed using the Stanford-Binet Intelligence Scale, 4th edition; X-inactivation studies were also conducted.
Main Results:
- A clear hierarchy of cognitive abilities was observed: normal > carrier > affected.
- Mean composite IQ scores were 90.8 for normal individuals, 65.0 for carriers, and 43.2 for affected individuals.
- Carrier females displayed mild to significant X-inactivation skewing, which did not significantly correlate with their IQ scores.
Conclusions:
- The study confirms significant intellectual deficits associated with Coffin-Lowry syndrome in both affected males and carrier females.
- Findings support the concept of negative intellectual consequences in carriers of X-linked mental retardation disorders.
- X-inactivation patterns in carriers contribute to the variability in cognitive function but do not fully explain the observed deficits.