Rett syndrome in Ireland: a demographic study

Abstract

Background: Rett syndrome (RTT) is a rare neurodevelopmental condition associated with mutations in the gene coding for the methyl-CpG-binding protein 2 (MECP2). It is primarily observed in girls and affects individuals globally. The understanding of the neurobiology of RTT and patient management has been improved by studies that describe the demographic and clinical presentation of individuals with RTT. However, in Ireland, there is a scarcity of data regarding individuals with RTT, which impedes the ability to fully characterize the Irish RTT population. Together with the Rett Syndrome Association of Ireland (RSAI), we prepared a questionnaire to determine the characteristics of RTT individuals in Ireland. Twenty-five families have participated in the study to date, providing information about demographics, genetics, familial history, clinical features, and regression.

Results: The results show that Irish individuals with RTT have comparable presentation with respect to individuals in other countries; however, they had a better response to anti-epileptic drugs, and fewer skeletal deformities were reported. Nonetheless, seizures, involuntary movements and regression were more frequently observed in Irish individuals. One of the main findings of this study is the limited genetic information available to individuals to support the clinical diagnosis of RTT.

Conclusions: Despite the limited sample size, this study is the first to characterize the RTT population in Ireland and highlights the importance of having a swift access to genetic testing to sharpen the characterization of the phenotype and increase the visibility of Irish individuals in the international RTT community.

Keywords: MECP2 gene; Neurodevelopmental disorder; Rett syndrome.

Fig. 1

Reported information on the various clinical forms of RTT diagnosed in individuals in Ireland. The left pie chart shows the percentage of different clinical RTT forms- typical, atypical and Rett-like as reported in our study cohort: 48% (n = 12) reported a diagnosis of typical RTT, 28% (n = 7) reported a diagnosis of atypical RTT, 4% (n = 1) reported a ‘Rett-like’ diagnosis, and 20% (n = 5) did not know their diagnosis. The right pie chart shows the different forms of atypical RTT reported by the participants: 14% (n = 1) reported speech variant, 29% (n = 2) reported ‘early seizure variant’, and 57% (n = 4) did not know the atypical RTT variant they were diagnosed with

Fig. 2

Reported information on the frequency and forms of seizures reported in individuals in Ireland. The larger pie chart shows the percentage of seizures as reported in our study cohort: 76% (n = 19) reported experiencing epileptic seizures, while 24% (n = 6) did not. The smaller pie chart shows the different forms of seizures reported by the participants: 32% (n = 6) exhibited tonic clonic seizures, 16% (n = 3) exhibited focal, absence or partial seizures, and the remaining 52% (n = 10) did not know the type of seizure they experienced

Fig. 3

Details of behavioural presentation of the individuals with RTT in Ireland. The bar chart shows the number of individuals displaying behaviours, relating to excitement, sadness, anxiety, difficulty sleeping during night, self-injury, and injury to others

Fig. 4

Details of diagnostic tests performed on the individuals with RTT in Ireland. The bar chart shows the number of individuals who underwent additional diagnostic tests including EEG, cardiac activity, breathing activity and imaging