Elsevier

Brain and Development

Volume 23, Issue 4, July 2001, Pages 208-211
Brain and Development

Guidelines
Guidelines for reporting clinical features in cases with MECP2 mutations

https://doi.org/10.1016/S0387-7604(01)00193-0Get rights and content

Abstract

An international group recommends that papers relating phenotypes to genotypes involving mutations in the X chromosome gene MECP2 should provide a minimum data set reporting the range of disturbances frequently encountered in Rett Syndrome. A simple scoring system is suggested which will facilitate comparison among the various clinical profiles. Features are described which should prompt screening for MECP2 mutations.

Introduction

Investigation of Rett Syndrome (RS) [1] entered a new phase with the discovery in 1999 of mutations in the MECP2 gene [2]. MECP2 is thought to control expression of several genes including some involved in brain development [3]. Many mutations have recently been identified in MECP2 and the percentage of Rett cases with mutations is rising steadily [4], [5], [6] - over 80% for classic RS in large studies, however it is clear that the absence of a demonstrable MECP2 mutation does not negate the clinical diagnosis of RS. Boys may be affected, probably less frequently than girls [7], [8]. Atypical/variant forms have been described with and without mutations and the pattern of X-chromosome inactivation influences severity [9]. Phenotype may also be influenced by the position and nature of the mutation and this requires further investigation [9]. Other genetic and non-genetic factors may also contribute to the presentation. Range of severity is wider than was initially apparent and clinical features not characteristically associated with Rett syndrome have been reported with MECP2 mutations [8], [9]. It is therefore clear that mutations in MECP2 underlie both RS and other phenotypes.

Important new questions have thus emerged for clinicians.

  • 1.

    Who should be tested for MECP2 mutations?

  • 2.

    Which clinical features will be of value in comparing different phenotypes?

To these the authors offer collective advice based on extensive clinical, epidemiological and genetic experience.

Publications on genotype-phenotype correlation should indicate diagnostic tests, giving the methodology of the MECP2 mutational analysis, describing mutations in standard nomenclature [10] and reporting concomitant genetic rearrangements such as chromosomal translocation or deletion elsewhere in the genome. The pattern of X-chromosome inactivation influences severity of the clinical disease in females and measurement in more than one tissue is desirable.

Section snippets

Who should be tested for MECP2 mutations?

Since disorders caused by MECP2 mutations may present in girls or boys as developmental delay, hypotonia, tremulous movement, poor feeding, poor mobility, fall-off in the growth of the head circumference and onset of epileptic seizures or non-epileptic vacant spells [1], [7], [8], [9], [11], mutation testing should be considered in screening infants with combinations of these problems although the value of screening awaits further confirmation. Testing now seems appropriate in later childhood

Clinical features for comparison of phenotypes associated with MECP2 mutations

It is essential to state age at clinical assessment and source of the clinical information

Discussion

Here we have drawn on international experience of RS surveys to provide a simple scoring system, completion of which provides a profile of commonly encountered, readily ascertained clinical features, to ease comparison between the various profiles associated with MECP2 mutations. The system may help in evaluation of effects of intervention, however for such studies specific objective measures should also be selected to match the problems under consideration. The fluctuating nature of the

Acknowledgements

We acknowledge our indebtedness to our many colleagues and the families and individuals with RS and especially to Andreas Rett for his initial observations, to Bengt Hagberg and his collaborators who championed the cause of Rett Syndrome research in English speaking countries and Kathy Hunter whose commitment laid a foundation for recent successes.

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