Imperial College London
Alternate

DrDeborahMorris-Rosendahl

Faculty of Medicine, National Heart & Lung Institute

Honorary Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7351 8412d.morris-rosendahl

 
 
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Location

 

2091Royal BromptonRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Kortüm:2011:10.1136/jmg.2010.087528,
author = {Kortüm, F and Das, S and Flindt, M and Morris-Rosendahl, DJ and Stefanova, I and Goldstein, A and Horn, D and Klopocki, E and Kluger, G and Martin, P and Rauch, A and Roumer, A and Saitta, S and Walsh, LE and Wieczorek, D and Uyanik, G and Kutsche, K and Dobyns, WB},
doi = {10.1136/jmg.2010.087528},
journal = {J Med Genet},
pages = {396--406},
title = {The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis.},
url = {http://dx.doi.org/10.1136/jmg.2010.087528},
volume = {48},
year = {2011}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Submicroscopic deletions in 14q12 spanning FOXG1 or intragenic mutations have been reported in patients with a developmental disorder described as a congenital variant of Rett syndrome. This study aimed to further characterise and delineate the phenotype of FOXG1 mutation positive patients. METHOD: The study mapped the breakpoints of a 2;14 translocation by fluorescence in situ hybridisation and analysed three chromosome rearrangements in 14q12 by cytogenetic analysis and/or array comparative genomic hybridisation. The FOXG1 gene was sequenced in 210 patients, including 129 patients with unexplained developmental disorders and 81 MECP2 mutation negative individuals. RESULTS: One known mutation, seen in two patients, and nine novel mutations of FOXG1 including two deletions, two chromosome rearrangements disrupting or displacing putative cis-regulatory elements from FOXG1, and seven sequence changes, are reported. Analysis of 11 patients in this study, and a further 15 patients reported in the literature, demonstrates a complex constellation of features including mild postnatal growth deficiency, severe postnatal microcephaly, severe mental retardation with absent language development, deficient social reciprocity resembling autism, combined stereotypies and frank dyskinesias, epilepsy, poor sleep patterns, irritability in infancy, unexplained episodes of crying, recurrent aspiration, and gastro-oesophageal reflux. Brain imaging studies reveal simplified gyral pattern and reduced white matter volume in the frontal lobes, corpus callosum hypogenesis, and variable mild frontal pachgyria. CONCLUSIONS: These findings have significantly expanded the number of FOXG1 mutations and identified two affecting possible cis-regulatory elements. While the phenotype of the patients overlaps both classic and congenital Rett syndrome, extensive clinical evaluation demonstrates a distinctive and clinically recognisable phenotype which the authors suggest designating as the
AU  - Kortüm,F
AU  - Das,S
AU  - Flindt,M
AU  - Morris-Rosendahl,DJ
AU  - Stefanova,I
AU  - Goldstein,A
AU  - Horn,D
AU  - Klopocki,E
AU  - Kluger,G
AU  - Martin,P
AU  - Rauch,A
AU  - Roumer,A
AU  - Saitta,S
AU  - Walsh,LE
AU  - Wieczorek,D
AU  - Uyanik,G
AU  - Kutsche,K
AU  - Dobyns,WB
DO  - 10.1136/jmg.2010.087528
EP  - 406
PY  - 2011///
SP  - 396
TI  - The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis.
T2  - J Med Genet
UR  - http://dx.doi.org/10.1136/jmg.2010.087528
UR  - https://www.ncbi.nlm.nih.gov/pubmed/21441262
VL  - 48
ER  -
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