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Jean-Christophe Roux - Restoration of BDNF metabolism to improve Mecp2 knock-out mice symptoms
Walter Kaufmann - Behavioral Problems in Rett Syndrome - An Emerging Issue
Aglaia Vignoli - The quality of life of rett people
Jennifer Mc Comas - Functional Communication Training for Individuals with Rett Syndrome- Breaking Down Geographic Barriers with Videoconferencing Technology 
Lotan Meir - Focus on walking with RS
Anne-Marie Bisgaard - Medical and physical follow-up of adults with Rett syndrome 
Mari Vold Henriksen - Epilepsy in Rett syndrome – from a lifetime perspective
Jeffrey Neul - Clinical Trials in Rett syndrome
Lotta Lintula - Eye-Gaze Technology As A Communication Device
Eeva-Liisa Metsähonkala - Epilepsy and RETT syndrome
Kaveh Vefagh - EyeGaze in Sensory and AAC


Helena Wandin - International Guidelines for the Management of Communication in Individuals with Rett Syndrome 
Gillian Townend, Assessing underlying skills of individuals with Rett syndrome
Jeffrey Neul - Autonomic Dysfunction in Rett syndrome
James Eubanks - Rett Syndrome from a Medical Research Perspective
Lotan Meir - Physical therapy in Rett syndrome
Jan-Marino Ramirez - The basis for breathing and  autonomic disturbances in RETT Syndrome
Samir Sethi - Indian Rett Syndrome Foundation
Anna Amato & Anne Berger - Potential and development of children with atypical Rett Syndrome (CDKL5 gene mutation) and Augmentative and Alternative Communication (AAC)
Alja van Maanen Oxygen - Rett19 Finland
Anne-Marie Bisgaard - Sleep disturbances in Rett syndrome 


COUNTRY UPDATES 2019 - Poster Session

Luennoitsijat  |  SPEAKERS

Anne-Marie Bisgaard

Anne-Marie Bisgaard is a consultant paediatrician specialized in neurodevelopmental disorders and rare diseases. She works at Center for Rett syndrome and Center for Rare Diseases at the University Hospital of Copenhagen, Rigshospitalet. Since 2011, she has been the head of the national Danish Rett center which was then established for both children and adults with Rett syndrome.

She did her PhD within the clinical genetic area in 2007 (The phenotype of patients with submicroscopic chromosomal abnormalities and mental retardation. Description of new microdeletion syndromes). Since then, her research focus has been on neurodevelopmental disorders, which in recent years mainly has been within Rett syndrome and related disorders and Cornelia de Lange syndrome. The focus is both on the molecular causes and mechanisms for disease and on clinical issues and how to manage these.  

Her clinical work focuses on different rare diseases, especially Rett syndrome. Individuals with Rett syndrome are followed lifelong on a regular basis by a multidisciplinary team. The visits result in an individual report concerning medical, physiotherapeutic, behavioral and communicative issues. The families also have access to advice from a dietician and a social worker associated the center.

Michelle Stahlhut


Michelle Stahlhut, PT PhD works as a research physiotherapist at the Danish Center for Rett syndrome. Michelle Stahlhut obtained her doctoral degree within disability research at Lund University in 2018. The primary area of her research is health promotion throughout life in individuals with Rett syndrome and she especially focuses on validation of outcome measures and development and evaluation of physical activity interventions.



Up-time participation in girls and women with Rett syndrome

Rett syndrome is associated with multiple disabilities including intellectual disability leading to a high level of dependency in all aspects of daily living including participation in physical activities. The different impairments and restrictions could have negative effects on the health and quality of life in those with Rett syndrome.

In Denmark 122 individuals are diagnosed with Rett syndrome in the ages of 2 to 64 years. A total of 105 in the cohort have a MECP2 mutation. At the Danish center for Rett syndrome we focus on optimal and lifelong health-promotion and also enhancing the quality of life of those affected with Rett syndrome and their families.

During the last 5 years the research at the Danish center for Rett syndrome has concentrated on three major areas: 1) Outcome measures, 2) Description of the population with Rett syndrome and 3) Development of a health-promoting intervention that focus on ‘uptime’ – that is standing and walking activities.

1) First of all it has been important to establish a toolbox of valid and reliable outcome measures and we have been involved in the validation of several outcome measures (Functional Mobility Scale – Rett Syndrome, Two-Minute Walk Test, Rett Syndrome Gross Motor Scale, ActivPAL, Quality of life inventory – Disability). Building the repertoire of outcome measures is valuable to both researchers and practitioners for intervention studies and clinical monitoring.

2) Secondly, we have described the patterns of sedentary time and steps across ambulation levels in 48 girls/women with Rett syndrome aged 5-60 years. On average 83.3% of waking hours were spent in sedentary behaviors (n=48) and the median daily step count was 5128 (n=28). Advancing age and poorer walking skills were associated with higher levels of sedentary time.

3) Finally, we have focused on the development of an ‘Uptime participation’ intervention which was evaluated in 14 girls/women with Rett syndrome aged 5-48 years. This intervention focused on participation in enjoyable activities to promote ‘uptime’ in home, school/day center and community settings. Primary outcomes were sedentary time and daily steps. Some of the secondary outcomes were walking capacity and quality of life. Significant positive effects were seen after the intervention in sedentary time (-4.1%), daily steps (+708 steps), walking capacity (+18.9m) and quality of life (+2.8 points).

Meir Lotan

Lotan Meir M.Sc.PT Ph.D. is a physical therapists from Israel. He´s working with girls with Rett syndrome over the past 26 years. He is a part of the Israel national evaluation team and has given consultations to about 500 girls with Rett syndrome across the globe. He works as a physical therapist with 15 girls on a regular weekly basis. He has written 30 articles and 4 books on Rett syndrome, and has done many research programs on this topic.



The presentation will describe appropriate physical therapy and physical activity programs in individuals with RS such as:

  • A functional and physical fitness improvements due to a daily treadmill, training program with children with RS
  • The results of a two year follow up on an intensive program through the Conductive Education (Peto) method
  • The results of an intensive regime for scoliosis at different ages
  • Sensory insights into Rett syndrome
  • The results of a home  program
  • The results o f a remote rehabilitation program


The presentation will suggest that intensive programs executed on a daily basis are capable of improving function, physical fitness, and outcome of scoliosis in children with RS. The presentation also suggests that such intensified programs can be executed by non-professional personnel, under the supervision of a qualified physical therapist.



The presentation will discuss different topics related to walking in Rett syndrome:

  1. Enhancing walking ability in young children with RS and CDKL5 using the UpSee device.
  2. Independent walking and loosing walking ability in RS over the years 
  3. Treadmill training for improving function and physical fitness in RS
  4. Regaining walking ability in an adult with RS after losing walking ability.
  5. Enhancing walking ability in a woman with RS using ABA method.  

Significance: The different research projects and case studies suggest that walking can be administered even in severe cases of RS, it can improve core element characteristics of RS, it can be regained in specific situation after it has been lost, and can be enhanced in individuals with RS who prefer to avoid walking.  

The presentation suggests specific tool for paraprofessionals working with this population to implement similar programs due to the importance of an active life style for those with or without disabilities.

James Eubanks, PhD

Dr. Eubanks is a neurobiologist at the Krembil Research Institute in Toronto, Canada – the home of the world champion Toronto Raptors. Dr. Eubanks came to Toronto in 1992, and started his own independent laboratory in 1994. The focus of his work at that time focused on defining how epigenetic factors influence the sensitivity of the brain to epilepsy and stroke. In the early 90’s, MeCP2 was one of a relatively small number of epigenetic factors that had been identified, which is why his group was examining MeCP2 before its role in Rett syndrome was revealed. With the identification in 1999 that MECP2 mutations cause Rett syndrome, his interests shifted towards delineating how MeCP2 normally regulates brain development and function, and to identifying how the absence of MeCP2 affects brain activity. By identifying deficits caused by MeCP2 dysfunction, his work has identified targets for rationale drug development programs working to develop Rett syndrome treatments. The first clinical trial based on his research has now received approval from Health Canada and will soon begin.


Dr. Eubanks’ group has shown that neural circuitry deficits in mouse models of Rett syndrome can be improved by reintroducing functional MeCP2 throughout the brain, and his group has shown that selectively preserving MeCP2 function in only a small number of neurons in the mouse brain is enough to significantly improve their Rett-like behaviour. His group uses a number of procedures for their investigations, which include molecular genetics, cell culture, fluorescence microscopy, EEG and electrophysiology, animal behaviour, and the use of embryonic stem cells to generate specific neurons and make new “personalized” mouse models engineered to express rare mutations that are now known to cause neurodevelopmental conditions. These models serve as the starting point for “precision medicine “investigations that will further our understanding of how the brain is affected in these rare genetic conditions.


Dr. Eubanks conducted his training in the United States, where he received a bachelor's degree from the University of California, Davis, and a PhD degree from the University of California, San Diego. Upon completion of his Doctoral degree, he then conducted postdoctoral training at the Salk Institute and at Duke University before coming to Toronto. He is currently a Senior Scientist and Division Head at the Krembil Research Institute in Toronto, and a Professor at the University of Toronto. He is member of the Scientific Advisory Board for the Ontario Rett Syndrome Association, the International Rett Syndrome Foundation, and the University of Toronto Epilepsy Research Program. His lab is currently funded by the Canadian Institutes of Health Research, the Ontario Brain Institute, the LouLou Foundation, and the National Institutes of Health.


Rett syndrome is a severe neurodevelopmental disorder that affects a few boys but mostly affects girls. Spontaneous mutations of the MECP2 gene are the largest cause of Rett syndrome, but how deficiencies in MeCP2 function facilitate Rett syndrome pathogenesis remains largely unknown. Our work shows that increased levels of oxidative stress within cells may play a role, as administering an anti-oxidant / mitochondrial vitamin cocktail solution to MeCP2-deficient neurons improved their functional properties, and administering the same cocktail to MeCP2-deficient mice improved some of their Rett-like behavioural deficits. These results led us to question how chronically increased oxidative stress might affect biochemical signaling systems in MeCP2-deficient systems. Our cells have surveillance receptors that normally only become activated in times of need, and usually for only a short period of time. We questioned whether one of the key surveillance receptor systems present in neurons might become chronically overactive in the MeCP2-deficient brain. Our results suggest this is the case, as the expression of the surveillance receptor was dramatically increased in the MeCP2-deficient mouse brain. Importantly, restoring the expression of this receptor back to normal levels using genetic procedures significantly improved MeCP2-deficient mice. The “treated” mice regained near normal mobility, showed improved anxiety-like behaviour, and had greatly reduced numbers of epileptic discharges. These results therefore identify a new system involved in Rett syndrome pathogenesis, and suggest that it may be targetable for therapeutic development.

Gillian Townend

Gill Townend, M.Phil., B.Med.Sci.(Speech)(Hons), CertMRCSLT, is a researcher at the Rett Expertise
Centre Netherlands – GKC, Maastricht University Medical Centre (MUMC+). She also works for Rett UK’s
communication and education project.
She is a speech and language therapist with longstanding clinical and research experience, initially

specialising in Augmentative and Alternative Communication (AAC) and more recently in Rett syndrome.

Her current research interests include: development of clinical guidelines for the management of
communication in individuals with Rett syndrome; eye tracking in individuals with Rett syndrome and
the functional use of eye gaze for communication; developing alternative assessments for measuring
receptive language and cognition in Rett syndrome; early (pre-diagnosis) communication development
in individuals with typical and atypical Rett syndrome; and the establishment of clinical and research-
based networks and collaborations within and outside of Europe. In her clinical work she also runs
support groups and ‘out and about’ communication groups for individuals with Rett syndrome and their

She was responsible for organising the ‘communication track’ of the 3 rd European Rett Syndrome
Conference Maastricht in 2013, is co-founder of two national networks for Speech and Language
Therapists working with individuals with Rett syndrome – in the Netherlands and the UK, is the
European representative on the North American Rett Clinics Network, and is co-ordinator of the
international project to develop communication guidelines for Rett syndrome.

Researcher, Rett Expertise Centre Netherlands – GKC

Title of presentation:
Oculomotor function in individuals with Rett syndrome

Gillian S. Townend a , Raymond van de Berg a,b,c , Laurèl H.M. de Breet d , Monique Hiemstra d,1 , Laura Wagter d ,
Eric Smeets a , Josine Widdershoven b , Herman Kingma b,c , Leopold M. G. Curfs a

a Rett Expertise Centre Netherlands – GKC, Maastricht University Medical Center, Maastricht, The
b Division of Balance Disorders, Department of Otorhinolaryngology and Head and Neck Surgery,
Maastricht University Medical Center, Maastricht, The Netherlands.
c Faculty of Physics, Tomsk State University, Tomsk, Russia.
d Faculty of Medicine, Maastricht University, Maastricht, The Netherlands.

Background: Individuals with Rett syndrome (RTT) rely on eye pointing/eye gaze as a primary means of
communication. Underlying an ability to communicate successfully with the eyes is a complex matrix of
requirements, with an intact oculomotor system being one element. To date, the underlying neural and
motor pathways associated with eye gaze are relatively under-researched in RTT.

Material and Methods: The eye movements of 18 girls and young women with RTT were assessed by
electronystagmography (ENG). This tested horizontal saccade and smooth pursuit (SP) eye movements,
optokinetic nystagmus (OKN) and vestibulo-ocular reflex (VOR). Results were compared to normative
data collected from 16 typically-developing (TD) children and teenagers.

Results: Overall, the RTT cohort demonstrated a range of eye movements on a par with the TD group; all
those who yielded a measurable result showed SP and saccadic eye movements, OKN and VOR. Two
areas of potential difference were (i) Saccades latency where the RTT cohort exhibited a longer latency,
and (ii) VOR where the RTT group demonstrated a slower fast phase velocity. There were, however,
greater difficulties in executing the ENG testing with the RTT cohort which made quantitative analysis
tricky. For example, reduced motivation and attention to test materials and low quality electrode

Conclusions: “Eye-pointing can be seen as the integrated outcome of a combination of visual, social,
cognitive and motor skills” (Sargent et al, 2013). The starting point for assessing this matrix of
requirements is whether an individual can maintain and shift fixation of gaze. This study addresses that
question and suggests that individuals with RTT have an intact oculomotor system, although potential
differences in saccades latency should be explored further. Modifications should be made to traditional
ENG assessment to combat problems in testing and add strength to the results.

Walter E. Kaufmann, MD

Dr. Walter E Kaufmann is the Chief Medical Officer of Anavex Life Sciences Corp. He
has over 20 years of experience in clinical studies with focus on developing novel
therapies for genetic disorders associated with intellectual disability. Prior to Anavex, Dr.
Kaufmann was the Director of the Center for Translational Research at the Greenwood
Genetic Center, where he also held the Ravenel Boykin Curry Chair in Genetic
Therapeutics. He holds adjunct appointments at Emory University School of Medicine,
where he is an Adjunct Professor of Human Genetics, and at the University of California
Davis School of Medicine, where he is a Visiting Scholar in the Department of
Neurology. Dr. Kaufmann is also an Investigator affiliated with the Massachusetts
Institute of Technology’s Simons Center for the Social Brain. Before these academic
appointments, Dr. Kaufmann was a Professor of Neurology at Harvard Medical School
and a Professor of Pathology, Neurology, Pediatrics, Psychiatry, and Radiology at the
Johns Hopkins University School of Medicine.

Dr. Kaufmann’s major research focus has been Rett syndrome, a field where he has
published extensively on neurobiology and clinical aspects with a focus of behavioral
problems. He served as founder and leader of RettSearch, the international consortium
of Rett syndrome clinical researchers. As such, he co-authored the current diagnostic
guidelines for the disorder. He also edited the first clinical textbook on Rett syndrome,
published in late 2017. Dr. Kaufmann has also served as Co-Principal Investigator of the
NIH-funded Natural History Study of Rett syndrome (RDCRN program). He has also led
efforts at developing biomarkers and outcome measures for Rett syndrome and fragile X
syndrome. Dr. Kaufmann has played different roles, including site investigator, Principal
Investigator, and DSMB member/chair, in almost 20 drug trials for neurodevelopmental
disorders. In this context, he has been involved in virtually all neurobiologically-based
drug trials for Rett syndrome. His research has been funded by the NIH, DOD, CDC (he
is member of the Steering Committee for the CDC natural history study of fragile X
syndrome funded by CDC), and by research foundations including

Dr. Kaufmann has published more than 220 journal articles, most of them original
publications. He has also served on several editorial boards and as reviewer for over
100 scientific journals. Dr. Kaufmann was also member of the Neurodevelopmental
Disorders Work Group of the Diagnostic and Statistical Manual of Mental Disorders-Fifth
Edition (DSM-5), which developed the current diagnostic guidelines for intellectual
disability and autism spectrum disorder.

Jan-Marino Ramirez

Jan-Marino (Nino) Ramirez, PhD is a Professor of Neurological Surgery and Director of the Center for Integrative Brain Research at the Seattle Children’s Research Institute.

Dr. Ramirez studies neural mechanisms involved in the generation of respiratory rhythms, neocortical activity, and epilepsy. He has conducted research investigating the neuronal mechanisms underlying erratic breathing and dysautonomia in Rett syndrome in animal models and children. In collaboration with Drs. D. Weese-Mayer and M.S. Carroll he uses quantitative methods to perform a breath-to-breath analysis and the coordination with the heart.

He also studied familial dysautonomia, congenital hypoventilation syndrome, pediatric epilepsy, and he explores the mechanisms leading to sleep apnea and SIDS. Dr. Ramirez’s work has been funded by multiple National Institutes of Health (NIH) grants since 1996.

Liisa Metsähonkala

Present position: Pediatric neurologist and deputy chief in Epilepsy Unit for Children and Adolescents, Pediatric Neurology clinic, start date 2.1.2005.

James M. Youakim


Investigation of Trofinetide as a Treatment of Rett Syndrome

Trofinetide is a synthetic analogue of glycine-proline-glutamate (GPE), the n-terminal tripeptide of the
insulin-like growth factor 1 (IGF-1) (Guan et al. 2015). There is evidence from preclinical studies that GPE may benefit patients with Rett syndrome (RTT) (Tropea et al. 2019; Williams et al. 2014).

A recent Phase 2 clinical study evaluated treatment with trofinetide compared with placebo in 82 girls
with Rett syndrome aged 5 to 15 years (Glaze et al. 2019). At the highest dose (200 mg/kg twice daily
[BID]), trofinetide achieved statistically significant improvement compared with placebo on 3 of 5
syndrome-specific efficacy measures: (1) the Rett Syndrome Behaviour Questionnaire (RSBQ), a
caregiver assessment (P=0.042), (2) the Clinical Global Impression Scale-Improvement (CGI-I), a clinician assessment of the improvement of Rett syndrome (p=0.029), and (3) the RTT-Clinician Domain Specific Concerns-Visual Analog Scale (RTT-DSC), a clinician assessment (p=0.025). Results of the study also showed trofinetide was well-tolerated at all dose levels (50 mg/kg BID, 100 mg/kg BID, and 200 mg/kg BID).

A 12-week, Phase 3, double-blind, randomized, placebo-controlled study will begin this year to evaluate efficacy and safety of trofinetide and placebo in a 1:1 ratio in 184 females 5 to 20 years old with RTT. The study will use the RSBQ and the CGI-I syndrome specific efficacy measures as co-primary efficacy endpoints. The double-blind study will be followed by a 9-month, open-label extension study in which all participants, including those on placebo in the Phase 3 study, will be eligible to receive trofinetide. In the open-label extension study, all participants will be followed to evaluate long term tolerability and safety of trofinetide in girls and women with Rett Syndrome.

Author Summary:
James M. Youakim, M.D., is Vice President, Translational Research and External Innovation, at ACADIA
Pharmaceuticals Inc. He attended medical school and completed training in psychiatry at Baylor College of Medicine in Houston and has been working in the pharmaceutical industry on the development of central nervous system medications since 2006.

Helena Wandin


Helena Wandin is a Speech language therapist at the Swedish National Center for Rett syndrome and related disorders and a PhD student at Uppsala University. Her main interest is communication. She is part of the project group that develops guidelines for management of communication in Rett syndrome.


Title: International Guidelines for Management of Communication in Rett

Authors: Wandin, Helena (Sweden)1,2; Townend, Gillian (Netherlands)3; Curfs, Leopold Mg (Netherlands)3; Bartolotta, Theresa E (United States of America)4; Urbanowicz, Anna (Australia)5

Affiliatons: 1 - Swedish National Center for Rett Syndrome and Related Disorders,
Frösön; 2 - Department of Public Health and Caring Sciences, Uppsala University,
Uppsala; 3 - Rett Expertise Centre Netherlands – GKC, Maastricht University
Medical Center, Maastricht; 4 - School of Education, Monmouth University, NJ; 5 –
Social and Global Studies Centre, School of Global, Urban and Social Studies, RMIT
University, Queensland

Families of individuals with Rett syndrome report their struggles to access appropriate, knowledgeable, timely and ongoing support tailored to the individual’s specific communication needs. The aim of this project was therefore to develop rigorous international clinical guidelines for the assessment, intervention and long-term management of communication in individuals with Rett syndrome.

An expert panel consisting of 36 experienced professionals and caregivers reviewed draft guidelines through a two-stage modified Delphi study. These draft guidelines were based on the results of a literature review and international online surveys for communication professionals and caregivers. The experts reported their agreement with the statements in the draft guidelines using a Likert scale and added additional comments in response to questions about the statements. The final set of
guidelines that were developed through consensus consists of statements that reached a threshold of >70% agreement. The guidelines are based on more than 300 articles, drawn from literature relating to Rett syndrome as well as augmentative and alternative communication and clinical practice documents.

More than 400 caregivers and 120 communication professionals from over 30 countries completed the online surveys. The expert panel reviewed a comprehensive list of statements in the Delphi process
many of which reached the preset level of consensus.

The final international guidelines and a handbook for management of communication in individuals with
Rett syndrome will be described and exemplified in this presentation.

Anna Amato & Anne Berger

We are a practice for speech therapy and Augmentative Alternative
Communication (AAC). Anna Amato is the practice owner, a qualified
rehabilitation pedagogue, academic speech therapist, integrative learning
therapist and lecturer at the Catholic University of Applied Sciences
Berlin. She is working with ACC for 20 years. Anne Berger is a qualified
rehabilitation pedagogue and works in the practice of Ms. Amato.

Mari Wold Henriksen

Mari Wold Henriksen is a clinician working at the Department of Neurology and the Adult
Habilitation Centre, Vestre Viken Hospital Trust, Drammen, Norway. Dr Henriksen submitted her
thesis, Rett syndrome – clinical and genetic aspects, in June and is awaiting a date to defend. The
thesis focuses on health, and especially epilepsy, in adults with Rett syndrome and the phenotypic
and genotypic variation in Rett syndrome and differences in clinical characteristics between
individuals with different genotypes. As a clinician Dr. Henriksen has been responsible for the
medical follow up for adults (>16 years) with Rett syndrome in her area since 2014.

TITLE OF PRESENTATION: Epilepsy in Rett syndrome – from a lifetime perspective
The presentation will describe clinical characteristics of epilepsy in Rett syndrome in different phases
of life with, supported by data from both a literature review and our own research. The abstract
below summarizes our article “Epilepsy in classic Rett syndrome – course and characteristics in adult

AUTHORS: Mari Wold Henriksen, Hilde Breck, Stephen von Tetzchner, Benedicte Paus, Ola H.
Skjeldal, Eylert Brodtkorb

PURPOSE Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects
females. Epilepsy is a major clinical feature, but its long-term course in RTT has not been sufficiently
explored. This study addresses the development of the epilepsy in adults with RTT.

METHODS Available females diagnosed with RTT in Norway were asked to participate.
Parents/caregivers were interviewed, the girls/women were examined and their medical records
reviewed. Participants were categorized according to age, epilepsy, seizure patterns and mutation
severity groups. RTT severity was assessed (epilepsy score excluded).

RESULTS 70 females were included. The presence of active epilepsy (seizures last five years) was
similar in all age groups above the age of ten: 11 (65%) in adolescents (11-20 years), 9 (60%) in young
adults (21-30 years) and 14 (67%) in participants above 30 years of age. Tonic-clonic seizures within
the last year were present in 55, 67 and 64%, and ≥weekly seizures occurred in 27, 45 and 50% in the
respective age groups. In the oldest group (>30 years), only 19% had obtained seizure control for >5 years, and 14% had never experienced seizures. Seizure activity correlated with RTT severity score, whereas the relationship to mutation type remained ambiguous.

CONCLUSION Epilepsy continues to be a major concern in adults with RTT. Two thirds of women
above 30 years of age remained with active epilepsy and 50% of them had seizures at least weekly.

Aglaia Vignoli

Aglaia Vignoli is Associate Professor in Child Neurology and Psychiatry at the Department of Health
Sciences, University of Milan, Italy. Her research expertise focuses on the neurological aspects of Rare
Diseases, mainly regarding epilepsy and neurophysiological characteristics. One of her main research
interests is Rett Syndrome (RTT). In the last years, she contributed to further characterizing the
neurophysiological features of this syndrome (e.g. stereotypies, response to antiepileptic drugs,
neurophysiological and cognitive characteristics).

Working in a multidisciplinary team, she coordinated a panel of consultants in Italy, and developed recommendations for the diagnosis and management of RTT (published online at: Thanks to her expertise in the diagnosis and follow-up of patients with RTT, she has been involved in the development and implementation of the Rett Network Database (, as a local Coordinator.

In collaboration with a group of physicians and geneticists, she also characterized the electro-clinical phenotype of MECP2 Duplication Syndrome, and supported the research about the immunological aspects of this syndrome.

ABSTRACT Quality of life of people with Rett Syndrome

Living with a complex rare disease such as Rett Syndrome has a considerable impact on individuals affected and their families. This is true not only considering medical issues, but also their physical, psychological, and social wellbeing, areas that have been identified as determinant for the quality of life (QOL) of individuals with the disorder. Although many QOL measures can be used for children or people with intellectual disability, none of them captured the complexity of Rett Syndrome. Only recently, new tools targeted for systematically explore QOL in people with Rett Syndrome have been developed.

The instruments used to measure QOL of Rett girls, focused on parents’ interviews, identified both qualitative and quantitative parameters. In most studies, severity of illness, ability to communicate and age are the most frequent variables related to QOL. It is important to identify which areas of QOL are specifically affected in Rett Syndrome in order to address useful future care, which should provide intervention targeted not only to health problems management but also to social and environment actions. These kind of interventions may be able to improve the QOL of patients and their families as a whole.

Lotta Lintula

Lotta Lintula Lotta Lintula works as a speech and language pathologist in Tampere University Hospital Outpatient clinic for persons with intellectual disability. Clinical work with RS led her to conduct her doctoral research in Tampere University on eye-gaze technology in aided communication used by persons with RS.


Reliable outcome measure of linguistic ability of a person with RSis extremely challenging due to severe motor and communication limitations. In addition, when a person cannot diversely communicate views about his/her own habilitation, the decision-making lies heavily on interpretations of the caretakers and health professionals. The aim of this study was to find out how the parental view of the habilitation process reflects to the emphases in professional reports, when describing the habilitation process learning to use the eye-gaze technology as a communication aid.

Three teenage girls with RS took part in a three-year habilitation process. The professional reports were written to document participants’ ability of function and progress in it, to define goals for the habilitation and to describe the habilitation process. Parents were interviewed, focusing on their experiences of the process. The International Classification of Functioning, Disability and Health (ICF) was used in content analysis of the data.

All subjects learned to use eye-gaze technology as a communication aid. When professionals reported about the communication, they typically described how a participant expressed a certain subject, and the improvement in communication was commonly described as a new skill achieved. Parents, however, were more focused on the meanings of the communication rather than means. The parental interviews included descriptions of changes in participation possibilities of the participants rather than new skills. Both parents and professionals considered the participant’s motivation as an important factor.

In parental interviews the motivation was the most often mentioned causal factor in general. In professional reports the motivation of the participant was seen as a causal factor in task performance, watching and communication. The influence of this was regarded as directive of at least difficult to overcome. Some contradictory views among the parents and professional during the habilitation were documented, that could be explained by the different interpretations about the participant’s ability to function.

Alja van Maanen

Alja frequently shares her story, her own experience as an “expert parent", with groups of parents, carers and other professionals. She shares her perspective, that of a parent in a family caring for a child with complex needs, and through this, aims to raise awareness of the impact that having a child with severe multiple disabilities has on the whole family and what that family needs.



Enrico Tongiorgi

Mirtazapine as new potential treatment for Rett syndrome

Javier Flores Gutiérrez 1 , Claudio De Felice 2 , Giulia Natali 1 , Silvia Leoncini 3 , Cinzia Signorini 4 , Joussef Hayek 3 , Enrico Tongiorgi 1
1 Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
2 Azienda Ospedaliera Universitaria Senese, Neonatal Intensive Care Unit, 53100 Siena, Italy
3 Azienda Ospedaliera Universitaria Senese, Child Neuropsychiatry Unit, 53100 Siena, Italy
4 Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy

The X-linked neurodevelopmental disorder Rett syndrome (RTT) is caused primarily by mutations in a
transcriptional regulator, methyl CpG–binding protein 2 (MECP2). RTT presents a complex and variable
symptomatology, characterized by intellectual disability, motor deficits, cardiorespiratory alterations and epilepsy. Currently, there is no cure for RTT. Several symptomatic treatments have extended life
expectancy, but quality of life worsens as patients get older. Antidepressants have emerged as potential treatments against RTT, as they could normalize low monoamines transmission found in this disease.

Mirtazapine is a highly tolerated tetracyclic antidepressant that specifically increases noradrenergic and
serotoninergic transmission. We previously showed that this drug is able to rescue cortical atrophy, anxiety phenotype, respiratory and hearth rhythms and GABAergic and Glutamatergic transmission in a male RTT mouse model; however, more information on the effects of this drug in female RTT is needed.

In this study, we firstly evaluated the effects of a 30-days mirtazapine treatment (10mg/Kg) on neuroanatomical and behavioral phenotypes in 6-month-old adult heterozygous MeCP2 +/- female mice. No adverse events were found in female mice during treatment. We found that mirtazapine has a mild effect on motor coordination as it prevented worsening of motor deficits, tested on a dowel-test. Moreover, we found a striking complete normalization of the abnormal behavior in the elevated plus maze, which we demonstrated to be due to whiskers hypersensitivity. The normalization of motor and sensory abnormalities correlated with a rescue of parvalbumin normal levels in neurons of the motor cortex and somatosensory cortex but not in amygdala.

Secondly, based on these promising pre-clinical results, we retrospectively analyzed medical records from 11 adult RTT patients (16-42 years-old, mean 26.9y) having received mirtazapine for 1-5 years (mean 2.3y) to treat anxiety and sleep disturbances, with respect to 11 untreated age-matched RTT patients.

Mirtazapine treatment was well tolerated in 9/11 patients and induced improved RCSS and MBAS scores.In particular, for 9 MBAS scores we found that mirtazapine either prevented worsening or promoted an improvement of the symptoms. Thirdly, using an in vitro model of RTT we found an involvement of the BDNF/TrkB signaling cascade in the mechanism of action of mirtazapine. These results strengthen the hypothesis that Mirtazapine may represent a new potential treatment for RTT patients.

Jennifer J McComas

Dr. McComas is Professor of Special Education/Educational Psychology and is a Rodney S.
Wallace Professor for the Advancement of Teaching and Learning at the University of
Minnesota. Her translational research informs both basic behavioral science and applied
interventions for improving early communication and addressing severe problem behavior. She
directs a telehealth lab which overcomes geographic barriers to allow frequent interactions with
families of individuals with complex communication needs, intellectual and developmental
disorders, and severe behavior problems. Dr. McComas has over 70 peer-reviewed empirical
research papers and her research has been funded by the National Institutes of Health and the US
Department of Education. She has served as Editor-in-Chief of the Journal of Behavioral
Education, former Associate Editor of the Journal of Applied Behavior Analysis, and currently
serves as guest Associate Editor and on the editorial board of a number of scholarly journals.

Yolanda van Boven


My name is Yolanda van Boven, I am married to Rob and together we have
three children. We live in the Netherlands. Last year I wrote a book to our
eldest daughter Floortje, “Dear Floortje, your story, our special life”.**
In this book I tell her how she brings up the best in me, every day. How she
adds color to our life, sometimes painfully intense and heavy but above all
beautiful and filled with love.
I will tell you her story and our life, which has been defined by Rett-syndrome
for 18 years. I want to share my feelings about emotions, about fear, about
happiness and above all the love that connects us all together.

Dear Floortje,
Ultimately, our wish to have a healthy child didn't come true, our lovely visions
were driven away by the diagnosis of Rett Syndrome.
Foremost it makes me sad that it's so hard on you, each day and again. I'm also
angry that you are the one who has to bear it all. You are disabled, you are the
one with pain and discomfort, you will be dependent of others the rest of your
life. I feel helpless not being able to give you a long and happy life. We can only
offer you a hard and vulnerable life in which we can't do more than idly
standing by. We have to be strong.
And that we are. Since above all our feeling of joy remains. Every day we are
aware of all the beauty you give us and we're capable of enjoying this.  Your
view on the world is pure, you speak with your eyes and you talk with your
heart. You show us what it's really about. It's not about having more, not about
the grass being greener, not about what we don't have. You teach us that we
have to look beyond your disabilities to see your possibilities.
Dear Floortje, you've shown us what happiness is and that we ourselves are
responsible for experiencing and enjoying these feelings.

**(“Lieve Floortje, jouw verhaal, ons bijzondere leven”
is only available in Dutch).

Jean-Christophe Roux

Dr. Roux has a long-standing interest in developmental neurophysiology that started during his PhD obtained at the University of Lyon in 2000 and continued with the study of the respiratory control and its neonatal development as a postdoc, in the Karolinska institute. His expertise in breathing control lead him to work on Rett syndrome and Dr. Roux was part of one of the first team describing breathing defects in a preclinical model of Rett syndrome. Following on these results, Dr. Roux proposed a pharmacological treatment able to improves breathing defects and to increase the lifespan of a Rett mouse model, which laid the groundwork for a phase IIa clinical trial under the supervision of Professor Josette Mancini (Pediatric Neurology Dpt., Marseille University Hospital). Thereafter, focusing on other systems affected by Mecp2, Dr. Roux made an important discovery demonstrating that axonal transport was altered in the absence of Mecp2 and that cysteamine treatment, known to restore intracellular dynamics and BDNF secretion, improved lifespan and motor deficits in Rett mouse. The therapeutic potential of this molecule seemed very promising and a new clinical trial is currently being set up in Paris. More recently, we developed a project of genetic therapy using a codon-optimized mouse version of Mecp2 under the control of a short Mecp2 promoter, we have demonstrated the efficacy of our strategy to improve motor and autonomic phenotypes after tail vein injection of AAV9 vectors.

As a principal investigator in the field of Rett syndrome (RTT), Dr. Roux has authored more than 45 international peer-reviewed publications and has been the recipient of many national and international grants, including 2 Europeans networks (Dischrom, Eurorett).

In addition to research, Dr. Roux also teaches Neurophysiology in three different universities and is also invested in supporting Rett associations as a member of the Scientific Advisory Boards of the French Rett Syndrome Association (AFSR) since 2005. He also participates in scientific outreach initiatives such as those promoting research to the public (Telethon) and to the family of Rett patients (Rare disease day, AFSR meeting). 

Jeffrey Neul

Jeffrey Neul, MD, PhD, is the Director of the Vanderbilt Kennedy Center at Vanderbilt University Medical Center and Annette Schaffer Eskind Chair and Professor of Pediatrics, Pharmacology, and Special Education at Vanderbilt University. Dr. Neul’s research focuses on neurodevelopmental disorders with a genetic cause, specifically on Rett syndrome and related disorders. His work spans from laboratory based basic and translational work using animal and cellular models of disease, to clinical research on the natural history of disease progression and clinical trials in these disorders.

Dr. Neul has been the administrative head of the NIH funded Rett syndrome and related disorders Natural History Study, and has been involved in multiple completed and ongoing industry-sponsored trials in Rett syndrome. He currently is the principal investigator and IND-holder for oral ketamine in Rett syndrome. Additionally, he runs a translational laboratory evaluating biomarkers and conducting preclinical trials in disease models of Rett syndrome. Previously he was the Division Chief of Child Neurology at the University of California, San Diego, and before that he was on faculty at Baylor College of Medicine in Houston, Texas.