Genotype and early development in Rett syndrome: the value of international data.
BACKGROUND
Rett syndrome is a neurodevelopmental disorder mostly affecting females and caused by mutations in the MECP2 gene. Originally the syndrome was characterised as having a normal prenatal and perinatal period with later regression. Previous work has speculated that the girl with Rett syndrome may not be normal at birth.


OBJECTIVE
to examine whether early development between birth and ten months varies by genotype in Rett syndrome.


METHODS
cases were sourced from two databases, the Australian Rett Syndrome Database (est. 1993) and the newly formed InterRett - IRSA Rett Phenotype Database. Data available on 320 cases included information provided by parents on perinatal problems, early developmental behaviour and mobility. Problem scores, mobility scores and a total composite score for each mutation were generated and compared.


RESULTS
overall, 58% of respondents noted unusual behaviour during the first six months and 70.6% from the period between 6 and 10 months of life. Statistically significant differences were detected between some of the common mutations. Infants with R294X (P=0.05) and R133C (P=0.03) were less likely than those with R255X to have problems in the perinatal period. The most severe profile overall for early development was associated with mutations R255X and R270X.


CONCLUSIONS
This is the largest study to date examining the effects of individual mutations in Rett syndrome. With the ongoing case ascertainment and expansion of InterRett, sample size will increase rapidly and provide improved statistical power for future analyses. Results from this study will contribute to understanding the mechanism of early development in Rett syndrome and determining if and at which time(s) early intervention might be feasible.
Leonard
Helen
H
Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia. hleonard@ichr.uwa.edu.au
Moore
Hannah
H
Carey
Mary
M
Fyfe
Susan
S
Hall
Sonj
S
Robertson
Laila
L
Wu
Xi Ru
XR
Bao
Xinhua
X
Pan
Hong
H
Christodoulou
John
J
Williamson
Sarah
S
Klerk
Nick de
Nd
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D016208:Databases, Factual; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D038622:Internationality; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation; D012189:Retrospective Studies; D015518:Rett Syndrome / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology
D051783:Methyl-CpG-Binding Protein 2