Very mild cases of Rett syndrome with skewed X inactivation.

Background: Rett syndrome, a common cause of mental retardation in
females, is caused by mutations in the MECP2 gene. Most females
with MECP2 mutations fulfil the established clinical criteria for
Rett syndrome, but single cases of asymptomatic carriers have been
described. It is therefore likely that there are individuals
falling between these two extreme phenotypes. Objective: To
describe three patients showing only minor symptoms of Rett
syndrome. Findings: The patient with the best intellectual ability
had predominantly psychiatric problems with episodes of
uncontrolled aggression that have not been described previously in
individuals with MECP2 mutations. All three patients had normal
hand function, communicated well, and showed short spells of
hyperventilation only under stress. Diagnosis in such individuals
requires the identification of subtle signs of Rett syndrome in
girls with a mild mental handicap. Analysis of the MECP2 gene
revealed mutations that are often found in classical Rett syndrome.
Skewed X inactivation was present in all three cases, which may
explain the mild phenotype. Conclusions: Because of skewed X
inactivation, the phenotype of Rett patients may be very mild and
hardly recognisable.