Male Rett Syndrome - genetic diagnosis using oral mucosa swabs

Aims: Male Rett-Syndrome is extremely rare and associated with a very poor outcome. Rett-Syndrome is due to a mutation in the MECP2-Gen(Xq28). Two variants of the Rett-Syndrome are caused by mutations on the CDKL-5 Gen(Xp22) or the FOXG1-Gen(14q12). Here we present a 5-year-old boy with Rett-Syndrome together with the results of standard genetic testing from blood and mucosal swabs. Methods: Description of the clinical course including a video recording (from month 8 to 57). Due clinical signs suggestive of a male Rett-Syndrome standard genetic testing (MeCP2-Gen) was perfomed at the age of 20 months and 57 months of age. DNA from a mucosal swab was also used for genetic testing. Results: Developmental and medical history of the boy was unremarkable until one year of age. At the age of 16 months, progressive loss of cognitive, language, motor as well as socio-emotional skills became apparent. One month later, hand stereotypies, autistic behavior and hyperventilation developed in addition to a secondary microcephaly. He had no seizures. Genetic testing for MeCP2 mutations was negative at the age of 20 and 57 months. Mutation analysis using cells from a mucosal swab revealed a mutation in the MECP2 gene (c.502C>T). Testing of cells from urine showed a wild-type sequence. Conclusion: In the presence of symptoms highly suggestive of a Rett-Syndrome and negative testing for MECP2-Gens in DNA of blood cells a mosaic due to postcygotic de-novo mutation restricted to only one blastodermic layer should be considered. Testing cells obtained from a mucosal swab can then be used to support diagnosis. Further genetic testing of the parents with regard to the risk of recurrence is not indicated in this case. Male Rett-Syndrome - oral mucosa swab - blastodermic layer mosaic