Article title
Bebbington, A, Percy, A, Christodoulou, J, Ravine, D, Ho, G, Jacoby, P, Anderson, A, Pineda, M, Ben Zeev, B, Bahi-Buisson, N, Smeets, E & Leonard, H 2010, 'Updating the profile of C-terminal MECP2 deletions in Rett syndrome', Journal of Medical Genetics, vol. 47, no. 4, pp. 242-248. Download snapshot, see article abstract.
Background
A number of individual and groups of mutations in the MECP2 gene are associated with Rett syndrome. C-terminal deletions are a group of relatively small deletions of part of the MECP2 gene near one of the ends (the C-terminal end). They affect a small proportion (6-14%) of girls and women with Rett syndrome. Because these deletions occur at the 'end' of the gene, most of the gene is functioning normally, and so it was thought that those who have these mutations may have milder symptoms.
Therefore, we wanted to compare the features of girls and women with a C-terminal deletion with those with other MECP2 mutations. We also wanted to examine any differences amongst those with a C-terminal deletion.
What we did
For this study, we pooled information provided on over 800 individuals to the Australian Rett Syndrome Study and the International Phenotype Database, InterRett. We then translated this information into numerical scores and compared the scores between different mutation types.
What we found
Overall, girls and women with a C-terminal deletion tended to have milder symptoms compared to those with other mutations. These girls were also more likely to have learned to walk, maintained hand use and be of a normal weight and head circumference. Those with C-terminal deletions tended to develop other symptoms such as seizures, scoliosis and breathing issues, at a later age compared to those with otherMECP2 mutations.
Although muscle tone for these girls and women was more likely to be normal, kyphosis (similar to scoliosis but with forward spinal curve, rather than to the left or right) was also more common. They also developed hand stereotypies later than the others, which might mean that they may be diagnosed later, as hand stereotypies are known to be a 'hallmark' feature of Rett syndrome.
When we compared the symptoms of girls and women with different locations of the C-terminal deletions, those with a later deletion tended to have less severe symptoms compared to those with an earlier deletion.
What does it mean
This study provides a profile of the symptoms experienced by girls and women with a C-terminal deletion in the MECP2 gene. They are more likely to have learned to walk, maintain hand use and also tended to have a normal weight and head circumference compared to those with other MECP2 mutations. Only by combining Australian population-based and data from the International Phenotype Database, InterRett did we have the sufficient numbers to undertake this analysis. We are most grateful to participating families.