Is it possible to diagnose Rett syndrome before classical symptoms become obvious? Review of 24 Danish cases born between 2003 and 2012

Bisgaard, Anne‐Marie; Schönewolf‐Greulich, Bitten; Ravn, Kirstine; Rønde, Gitte

doi:10.1016/j.ejpn.2015.07.004

Cited by 13 publications

(15 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is not surprising that individuals with severe mutations are clinically diagnosed earlier, whereas less severe mutations are recognized much later. In addition, the early diagnosis of the atypical variants of RTT are generally difficult as clinical symptoms may be quite subtle initially (Bisgaard, Schonewolf‐Greulich, Ravn, & Ronde, ). An early diagnosis is particularly important because it gets patients off a potentially long and arduous diagnostic treadmill, restores reproductive confidence, and potentially gives patients access to the supportive therapy tailored to their needs.…”

Section: Discussionmentioning

confidence: 99%

RettBASE: Rett syndrome database update

2017

View full text Add to dashboard Cite

Rett syndrome (RTT) is an X-linked progressive neurodevelopmental disorder that primarily affects females. Mutations in the MECP2 gene have been attributed as the major genetic cause of RTT. Recently, mutations in CDKL5 and FOXG1 genes have also been suggested to give rise to RTT, although subsequent more extensive studies suggest that diseases resulting from mutations in these two genes should be considered as distinct clinical entities. While the genetic basis for the RTT has been recognized, so far there is no effective cure for the disease and the treatments available are mainly aimed at ameliorating clinical problems associated with the disorder. The swift identification of the mutations in children is crucial for pursuing the best therapeutic care. RettBASE was created in 2002 as a MECP2 variant database and has grown to become a comprehensive variant database for RTT and related clinical phenotypes, containing a curated collection of variants for MECP2, CDKL5, and FOXG1 genes. Here, we describe the development and growth of RettBASE after its inception in 2001. Currently, RettBASE holds a total of 4,668 variants in MECP2, 498 variants in CDKL5, and 64 variants in FOXG1.

show abstract

Section: Discussionmentioning

confidence: 99%

RettBASE: Rett syndrome database update

2017

View full text Add to dashboard Cite

show abstract

“…However, their diagnosis of RTT was delayed in most of the cases (2-6 years) presumably because of the male gender 11 or not even considered (Patient B) ( Table 1); whereas the corresponding mean age of the diagnosis in females with RTT in Denmark is 2.5 years. 18 Aside from the importance of raising clinicians' awareness of males with RTT, the present cases also illustrate the pitfalls in the diagnosis of mosaicism. Sanger sequencing is not the method of choice for detection of mosaicism.…”

Section: Discussionmentioning

confidence: 83%

Mosaic MECP2 variants in males with classical Rett syndrome features, including stereotypical hand movements

et al. 2018

View full text Add to dashboard Cite

Rett syndrome is rarely suspected in males because of the X-linked dominant inheritance. In the literature, only six male patients have been reported with methyl-CpG-binding protein 2 (MECP2) mosaicism. Next-generation sequencing (NGS) methods have enabled better detection of somatic mosaicism compared to conventional Sanger sequencing; however, mosaics can still be difficult to detect. We present clinical and molecular findings in two males mosaic for a pathogenic MECP2 variant. Both have been reexamined using deep sequencing of DNA isolated from four different cell tissues (blood, muscle, fibroblasts and oral mucosa). Deep sequencing of the different tissues revealed that the variants were present in all tissues. In one patient, the molecular diagnosis could only be established by reexamination after a normal whole exome sequencing, and the other case is an example of reverse genetic diagnostics. Rett syndrome should be considered in males with neurodevelopmental delay and stereotypical hand movements. Subsequent to clinical diagnosis males should be investigated with NGS-based technologies of MECP2 with high read depth and a low threshold for variant calls. If the initial analysis on full blood derived DNA fails to confirm the suspicion, we recommend repeating the analysis on another tissue, preferentially fibroblasts to increase the diagnostic yield.

show abstract

“…The majority of these findings stem from retrospective assessments, conducted through questionnaires/parental interviews (involving large databases such as InterRett or the Australian Rett syndrome database), retrospective trawls through pre-diagnostic medical records 44,45 or retrospective video analysis. 9–11,13,15–21,37 The prospective approach presented here is entirely novel to the field of studying RTT precursors.…”

Section: Resultsmentioning

confidence: 99%

“…Professionals need to be aware that parents are valuable informants about their child’s concurrent behaviors and should take their thoughts and concerns into account. 23,44 With early alerts, however, come professional and ethical/moral responsibilities, a duty to be able to offer early help and support to families. 10,53 Early detection also requires early intervention and this should not be forgotten.…”

Section: Resultsmentioning

confidence: 99%

Early development in Rett syndrome – the benefits and difficulties of a birth cohort approach

Marschik

Lemcke

Einspieler

et al. 2017

Developmental Neurorehabilitation

View full text Add to dashboard Cite

Purposes: Typically, early (pre-diagnostic) development in individuals later diagnosed with Rett syndrome (RTT) has been investigated retrospectively using parent reports, medical records and analysis of home videos. In recent years, prospective research designs have been increasingly applied to the investigation of early development in individuals with late phenotypical onset disorders, for example, autism spectrum disorder. Methods: In this study, data collected by the Danish National Birth Cohort lent itself to prospective exploration of the early development of RTT, in particular early motor-, speech-language, and socio-communicative behaviors, mood, and sleep. Results and Conclusions: Despite limitations, this quasi prospective methodology proved promising. In order to add substantially to the body of knowledge, however, specific questions relating to peculiarites in early development could usefully be added to future cohort studies. As this involves considerable work, it may be more realistic to consider a set of indicators which point to a number of developmental disorders rather than to one.

show abstract

Is it possible to diagnose Rett syndrome before classical symptoms become obvious? Review of 24 Danish cases born between 2003 and 2012

Cited by 13 publications

References 30 publications

RettBASE: Rett syndrome database update

RettBASE: Rett syndrome database update

Mosaic MECP2 variants in males with classical Rett syndrome features, including stereotypical hand movements

Early development in Rett syndrome – the benefits and difficulties of a birth cohort approach

Contact Info

Product

Resources

About