Huppke, P.; Maier, Esther M.; Warnke, A.; Brendel, C.; Laccone, F.; Gärtner, J.
Very mild cases of Rett syndrome with skewed X inactivation.
In: Journal of Medical Genetics, Vol. 43: pp. 814-816
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.