Rett syndrome in females with CTS hot spot deletions: A disorder profile

From a series of 107 females with Rett syndrome (RTT), we describe the long‐term history of ten females with a deletion in the C‐terminus of the MECP2 gene. We observed that their disorder profile is clinically recognizable with time and different from other atypical and milder RTT phenotypes. In females with hot spot deletions in the C‐terminus, dystonia is present from childhood and results in a serious spine deformation in spite of preventive measures. Their adaptive behavior is surprisingly better preserved and in contrast with the typical decline in motor functioning. The delineaton of disorder profiles by long‐term clinical observation can teach us about genotype/phenotype relationships and eventually about the effect of epigenetic phenomena on the final phenotype. © 2004 Wiley‐Liss, Inc.

[1]  M. Kyllerman,et al.  Odd MECP2-mutated Rett variant-long-term follow-up profile to age 25. , 2003, European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society.

[2]  Daisuke Hattori,et al.  DNA Methylation-Related Chromatin Remodeling in Activity-Dependent Bdnf Gene Regulation , 2003, Science.

[3]  Eric C. Griffith,et al.  Derepression of BDNF Transcription Involves Calcium-Dependent Phosphorylation of MeCP2 , 2003, Science.

[4]  H. Smeets,et al.  Rett syndrome in adolescent and adult females: Clinical and molecular genetic findings , 2003, American journal of medical genetics. Part A.

[5]  J. Fryns,et al.  Gross rearrangements in the MECP2 gene in three patients with rett syndrome: Implications for routine diagnosis of Rett syndrome , 2003, Human mutation.

[6]  A. Renieri,et al.  Rett syndrome: the complex nature of a monogenic disease , 2003, Journal of Molecular Medicine.

[7]  F. Hanefeld,et al.  An update on clinically applicable diagnostic criteria in Rett syndrome. Comments to Rett Syndrome Clinical Criteria Consensus Panel Satellite to European Paediatric Neurology Society Meeting, Baden Baden, Germany, 11 September 2001. , 2002, European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society.

[8]  P. Huppke,et al.  Influence of mutation type and location on phenotype in 123 patients with Rett syndrome. , 2002, Neuropediatrics.

[9]  U. Francke,et al.  Spectrum of MECP2 mutations in Rett syndrome , 2001, Brain and Development.

[10]  Masaya Segawa,et al.  Guidelines for reporting clinical features in cases with MECP2 mutations , 2001, Brain and Development.

[11]  P. Huppke,et al.  Mutation spectrum in patients with Rett syndrome in the German population: Evidence of hot spot regions , 2001, Human mutation.

[12]  H. Zoghbi,et al.  Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2 , 1999, Nature Genetics.

[13]  A. Wolffe,et al.  The methyl-CpG binding transcriptional repressor MeCP2 stably associates with nucleosomal DNA. , 1999, Biochemistry.

[14]  B. Hagberg,et al.  Rett variants: a suggested model for inclusion criteria. , 1994, Pediatric neurology.

[15]  B. Hagberg,et al.  Early stages of the Rett syndrome and infantile neuronal ceroid lipofuscinosis — A difficult differential diagnosis , 1990, Brain and Development.

[16]  F. Hanefeld,et al.  Rett syndrome: Criteria for inclusion and exclusion , 1985, Brain and Development.

[17]  Jean Aicardi,et al.  A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: Report of 35 cases , 1983, Annals of neurology.