Recurrent and founder mutations in the Netherlands: Extensive clinical variability in Marfan syndrome patients with a single novel recurrent fibrillin-1 missense mutation.

Background/Methods. Marfan syndrome (MFS) is a heritable connective tissue disorder usually caused by a mutation in the fibrillin 1 (FBN1) gene. Typical characteristics of MFS that have been described include dolichostenomelia, ectopia lentis and aortic root dilatation. However, there is great clinical variability in the expression of the syndrome's manifestations, both between and within families. Here we discuss the clinical variability of MFS by describing a large fourgeneration Dutch family with MFS.Results. Nineteen individuals of one family with a single missense FBN1 mutation (c.7916A>G) were identified. The same mutation was found in one unrelated person. Clinical variability was extensive and not all mutation carriers fulfilled the diagnostic criteria for MFS. Some patients only expressed mild skeletal abnormalities, whereas aortic root dilation was present in eight patients, an acute type A aortic dissection was recorded in two other patients, and a mitral valve prolapse was present in eight patients. In some patients cardiac features were not present on initial screening, but did however develop over time.Conclusion. MFS is a clinically highly variable syndrome, which means a meticulous evaluation of suspected cases is crucial. Mutation carriers should be re-evaluated regularly as cardiovascular symptoms may develop over time. (Neth Heart J 2010;18:85-9.).

Profiling Fragile X Syndrome in males: strengths and weaknesses in cognitive abilities.

The present study examined the cognitive profile in Fragile X Syndrome (FXS) males, and investigated whether cognitive profiles are similar for FXS males at different levels of intellectual functioning. Cognitive abilities in non-verbal, verbal, memory and executive functioning domains were contrasted to both a non-verbal and verbal mental age reference. Model-based cluster analyses revealed three distinct subgroups which differed in level of functioning, but showed similar cognitive profiles. Results showed that cognitive performance is particularly weak on measures of reasoning- and performal abilities confined to abstract item content, but relatively strong on measures of visuo-perceptual recognition and vocabulary. Further, a significant weakness was found for verbal short-term memory. Finally, these results indicated that the choice of an appropriate reference is critically important in examining cognitive profiles. The pattern of findings that emerged from the current cognitive profiling of FXS males was interpreted to suggest a fundamental deficit in executive control.