Elsevier

Brain and Development

Volume 24, Issue 5, August 2002, Pages 281-283
Brain and Development

Original article
Regression in individuals with Rett syndrome

https://doi.org/10.1016/S0387-7604(02)00058-XGet rights and content

Abstract

Data on features of regression and pre-regression developmental history in a case series of 53 girls and women with Rett syndrome are presented. Consistent with the diagnostic criteria, hand skills and verbal or non-verbal communication skills were the most common skills lost during regression. Play and motor skills were also lost in half the cases. Regression most commonly occurred between 12 and 18 months of age but was noted in a few cases before 6 months or after 36 months. Pre-regression developmental delays or abnormalities were noted in over two-thirds of cases, increasing to 85% of the youngest cases where parental reporting was likely to be more accurate. Age at regression was not associated with severity of physical and growth symptoms, and thus did not appear to be an index of neurological severity. There is a continuing need to further elucidate the pre- and post-regression features of Rett syndrome in order to aid early identification, diagnosis and referral for genotype mutation analysis.

Introduction

Regression is a defining feature of Rett syndrome. Loss of acquired purposeful hand skills accompanied by loss of communication skills form part of the necessary diagnostic criteria [1], [2], [3], [4], [5]. Although the diagnostic criteria state that developmental progress is within the normal range in the first 5–6 months of life, there is an emerging consensus that subtle abnormalities and even frank developmental delay is sometimes observed in cases who otherwise present with the classic syndrome [6], [7], [8], [9], [10]. Notwithstanding this, between 6 and 18 months, development slows or arrests. This stagnation of development is followed by a period of regression occurring between 1 and 3 years of age [11].

The general feature of regression has been well documented in clinical case series and large cohort studies [12], [13], [14]. However, detailed description of the range of skills lost may help elucidate the clinical course of the disorder and the identification of the pathogenic brain developmental processes that result from MECP2 mutations [15], [16], [17]. The present paper presents systematic data on regression in a large case series of girls and women (N=53) with Rett syndrome.

Section snippets

Method

Ethical approval for the study was granted by the Research Ethics Committee at the Institute of Child Health and Great Ormond Street Children's Hospital NHS Trust. Consent to participate was given by the parents and/or guardians of the individuals with Rett syndrome.

Data on regression was available on 53 cases from a larger case series (see Cass et al., 2002, in preparation). Forty-six cases met diagnostic criteria for classic Rett syndrome [1], [4] and seven cases criteria for an

Results

The data are summarised in Table 1. Due to the possibility that age of child at the time of report might affect accuracy of recall of features of regression and early development the data is presented by ageband. Twenty four were girls between 2 and 4 years of age (mean=3 years 3 months, SD=8.5 months), 15 were between 5 and 9 years (mean=7 years 4 months, SD=19.4 months), and 14 were adolescents and adults aged between 10 and 44 years (mean=24 years 4 months, SD=92.8 months).

The most common

Discussion

The mean age of regression (16 months) was similar to that reported in other studies [13]. There were a few outlying cases where regression was noted to occur earlier (two cases <6 months) or later (two cases >36 months) than is commonly reported. However, this has been found previously [12] and late regression can be considered as one variant of the Rett phenotype [3], [18], [19]. Loss of hand use was the most commonly reported feature of regression followed by verbal and non-verbal

Acknowledgements

The research was funded by the Rett Syndrome Association UK. Research at the Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from R&D funding received from the NHS Executive. The authors would like to thank the parents and carers and individuals with Rett syndrome for their assistance in this research.

References (20)

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