Rett syndrome with and without detected MECP2 mutations: an attempt to redefine phenotypes.
BACKGROUND
The diagnosis of Rett syndrome (RTT) is based on a set of clinical criteria, irrespective of mutation status. The aims of this study were (1) to define the clinical differences existing between patients with Rett syndrome with (Group I) and without a MECP2 mutation (Group II), and (2) to characterize the phenotypes associated with the more common MECP2 mutations.


METHODS
We analyzed 87 patients fulfilling the clinical criteria for RTT. All were observed and videotaped by the same paediatric neurologist. Seven common mutations were considered separately, and associated clinical features analysed.


RESULTS
Comparing Group I and II, we found differences concerning psychomotor development prior to onset, acquisition of propositive manipulation and language, and evolving autistic traits. Based on age at observation, we found differences in eye pointing, microcephaly, growth, number of stereotypies, rigidity, ataxia and ataxic-rigid gait, and severity score. Patients with truncating differed from those with missense mutations regarding acquisition of propositive words and independent gait, before the beginning of the disease, and microcephaly, growth, foot length, dystonia, rigidity and severity score, at the time of observation. Patients with the R168X mutation had a more severe phenotype, whereas those with R133C showed a less severe one. Patients with R294X had a hyperactive behaviour, and those with T158M seemed to be particularly ataxic and rigid.


CONCLUSIONS
A clear regressive period (with loss of prehension and language, deceleration of growth) and the presence of more than three different stereotypies, rigidity and ataxic-rigid gait seemed to be very helpful in differentiating Group I from Group II.
Temudo
Teresa
T
Unidade de Neuropediatria, Serviço de Pediatria, Hospital Geral de Santo António, Porto, Portugal. teresatemudo@hotmail.com
Santos
Mónica
M
Ramos
Elisabete
E
Dias
Karin
K
Vieira
José Pedro
JP
Moreira
Ana
A
Calado
Eulália
E
Carrilho
Inês
I
Oliveira
Guiomar
G
Levy
António
A
Barbot
Clara
C
Fonseca
Maria
M
Cabral
Alexandra
A
Cabral
Pedro
P
Monteiro
José
J
Borges
Luís
L
Gomes
Roseli
R
Mira
Graça
G
Pereira
Susana Aires
SA
Santos
Manuela
M
Fernandes
Anabela
A
Epplen
Jorg T
JT
Sequeiros
Jorge
J
Maciel
Patrícia
P
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D015518:Rett Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology
D051783:Methyl-CpG-Binding Protein 2