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Novel FOXG1 mutations associated with the congenital variant of Rett syndrome
  1. M A Mencarelli1,
  2. A Spanhol-Rosseto1,
  3. R Artuso1,
  4. D Rondinella1,
  5. R De Filippis1,
  6. N Bahi-Buisson2,
  7. J Nectoux2,
  8. R Rubinsztajn2,
  9. T Bienvenu2,
  10. A Moncla3,
  11. B Chabrol3,
  12. L Villard4,
  13. Z Krumina5,
  14. J Armstrong6,
  15. A Roche6,
  16. M Pineda6,
  17. E Gak7,
  18. F Mari1,
  19. F Ariani1,
  20. A Renieri1
  1. 1Medical Genetics, Department of Molecular Biology, University of Siena, Siena, Italy
  2. 2Université Paris Descartes, Institut Cochin, Inserm U567, Paris, France
  3. 3Inserm U910, Université de la Méditerranée, Assistance Publique Hôpitaux de Marseille, Hôpital de La Timone, Marseille, France
  4. 4Inserm U910, Université de la Méditerranée, Faculté de Médecine de La Timone, Marseille, France
  5. 5Medical Genetics Clinic of Latvian State, Children's University Hospital, Latvia
  6. 6Hospital Sant Joan de Déu, Esplugues, Barcelona, Spain
  7. 7Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer affiliated to the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  1. Correspondence to Alessandra Renieri, Medical Genetics, Molecular Biology Department, University of Siena, Viale Bracci, 2, 53100 Siena, Italy; renieri{at}unisi.it

Abstract

Background Rett syndrome is a severe neurodevelopmental disorder representing one of the most common genetic causes of mental retardation in girls. The classic form is caused by MECP2 mutations. In two patients affected by the congenital variant of Rett we have recently identified mutations in the FOXG1 gene encoding a brain specific transcriptional repressor, essential for early development of the telencephalon.

Methods 60 MECP2/CDKL5 mutation negative European Rett patients (classic and variants), 43 patients with encephalopathy with early onset seizures, and four atypical Rett patients were analysed for mutations in FOXG1.

Results and conclusions Mutations have been identified in four patients, independently classified as congenital Rett variants from France, Spain and Latvia. Clinical data have been compared with the two previously reported patients with mutations in FOXG1. In all cases hypotonia, irresponsiveness and irritability were present in the neonatal period. At birth, head circumference was normal while a deceleration of growth was recognised soon afterwards, leading to severe microcephaly. Motor development was severely impaired and voluntary hand use was absent. In contrast with classic Rett, patients showed poor eye contact. Typical stereotypic hand movements with hand washing and hand mouthing activities were present continuously. Some patients showed abnormal movements of the tongue and jerky movements of the limbs. Brain magnetic resonance imaging showed corpus callosum hypoplasia in most cases, while epilepsy was a variable sign. Scoliosis was present and severe in the older patients. Neurovegetative symptoms typical of Rett were frequently present.

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Footnotes

  • Competing interest None.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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