Study conducted in 2007, published 2013.
Thank you to all the people with MWS, their families, and their carers who participated in the study. Your time filling out questionnaires and completing the interviews is greatly appreciated. Many of you also expressed such enthusiasm for the study, which was very encouraging for those of us involved in the research. MWS is a relatively rare syndrome, and often when researching a rare syndrome it can be difficult to find a large enough group of willing participants. Without your time and dedication to the study, this research simply would not have been possible.
Thanks also to the many doctors, geneticists and pediatricians who forwarded information to participants on behalf of the research team. Their help in conducting this study was invaluable.
What is the study about
The study aimed to document the developmental and behavioral profile of people with MWS – that is, how do people with MWS develop and are there particular behaviors which are associated with MWS? Because no one has studied these issues in the past, the current study sought to explore these issues and document findings, rather than to test a particular theory.
What did the study involve
Participants in the study were 71 people with MWS and their parents, family members, and carers. The people with MWS ranged in age from 15 months to 50 years.
The study was conducted in three stages. Firstly, parents or carers of people with MWS completed a set of questionnaires about the person with MWS. These questionnaires asked about demographic information (such as age and gender), medical conditions associated with MWS, developmental milestones such as sitting up or walking, as well as a behavioral checklist, and a questionnaire about the person’s temperament. Five open-ended questions were included where parents or carers could give extra information. The questionnaires were translated into French, German, Italian and Japanese, and the behavior checklist was already available in 20 languages. A total of 71 sets of questionnaires were returned.
The second stage of the study involved the home visits, which included interviews with parents and carers, and a developmental assessment of the person with MWS. For children under the age of 9 years, the assessment used was the Griffiths Mental Development Scales. For those over 9 years, the assessment was comprised of a combination of tasks designed to assess the person’s understanding of language and problem-solving skills. In addition, a lot of information was gathered through observing the person with MWS and their interactions with people around them. The parent and carer interviews also provided valuable information regarding development. The interviews included a section focused on social skills, and another section designed to measure the types of behaviors often seen in people with autism. Another important component of the interviews was the collection of extra information provided by families and carers, which might otherwise have been missed if using questionnaires alone. 30 families took part in the developmental assessments and parent/carer interviews, and a further 9 families completed the parental interviews via telephone.
The third part of the study was the sleep questionnaire. This was sent only to those families where a parent was fluent in English. 35 sleep questionnaires were collected.
What were the main findings
Below are some findings from the study, when results were examined across the whole group. What is reported here are trends seen in the group. However, it is important to note that each person with MWS is an individual, and as such, each will have individual traits. The medical conditions associated with MWS vary between individuals, and so too do the behavioral and developmental aspects of MWS.
A person’s development and their behaviors are the result of a complex interplay of all of their genes (not just the ZEB2 gene which causes MWS), their life experiences, and their current environment. While the results of this study suggest some trends seen in people with MWS, they do not predict that an individual with MWS will necessarily display a particular behavior or trait.
It is also important to note that MWS was discovered only recently and at this point we are still learning about what features – both physical and behavioral/developmental -are associated with MWS. When a new syndrome is discovered, we often find that it is easier to recognize it in people who are more affected by the syndrome in the early days (for example, the people diagnosed with the syndrome may have very strong facial features, or a more severe degree of developmental delay, or they may have more medical problems). Over time, the syndrome might then also be recognized in people with less severe features (for example, their developmental delay might be milder, or their may have only a few or perhaps none of the medical features associated with the syndrome). This means that if you have a young child with MWS, or if your son or daughter was recently diagnosed, then the results presented here are not necessarily a prediction of what is to come.
One may ask then, what is the point of studying MWS? The purpose is to give information which might help people to better understand the syndrome, to draw attention to issues which could potentially be relevant for those involved in the care of a person with MWS, and to provide information which may help when planning interventions to enhance the care and quality of life of a person with MWS.
Degree of developmental delay or intellectual disability
For each person in the study, an estimate was made regarding their level of developmental delay or intellectual disability. This was based on all the available information about each person, including developmental assessments, parental interviews, observations, and responses to the questionnaires. Out of those who completed assessments, 79% were estimated to have an intellectual disability or developmental delay in the severe range, 7% within the profound range, and 14% in the moderate range. So, it can be seen that there is a wide variation in the abilities of people with MWS.
Strengths and weaknesses
The face-to-face and telephone interviews, which were conducted with 39 families, included the Vineland Adaptive Behavior Scales, which measures the person’s adaptive behavior in the areas of communication, daily living skills, socialization and motor skills. As a group, the people with MWS in the study showed weaker skills in the area of Daily living skills (such as feeding and dressing) compared with their own skills in other areas. However, the group showed a strength in socialization compared with other areas. Previously, some case reports published in genetics journals have suggested that people with MWS may show a strength in social skills. One aim of the study was to test if this was the case. The results suggested that many people with MWS do indeed show a strength in socialization compared with their own skills in other areas, and that across the whole group, people displayed more positive social behaviors than negative behaviors.
When looking at the raw scores for the Vineland scales, we saw a gradual increase in scores with increasing age – meaning that in general, those who were older generally showed more skills than those who were younger. But when scores were compared with those for typically developing children and adults, we saw that the gap between the abilities of people with MWS and those of the general population widened at older ages. This is simply because typically developing children make more rapid gains in development. The pattern of raw scores for people with MWS did indicate that with age, increases in actual skills were achieved. Also, during the interviews, some parents of older children and adults with MWS emphasized that their son or daughter had continued to learn and develop over their lifetime.
Age of reaching major milestones
The average age when people with MWS were reported to sit up without support was 21 months, but this ranged from 6 months to 5 years of age. The average age of walking independently was 3 years and 5 months, but again there was a large range of differences between people, with some walking at 18 months and others at 8 years of age.
At least half of those who had attempted toilet training had achieved some form of success with toilet timing or partial or full toilet training. Because some of the people who were currently attempting toilet training were still quite young, results were also examined just for the adults in the study. Out of those aged over 18 years who had attempted toilet training, 60% had achieved either toilet timing, toilet training during the day, or full toilet training both day and night.
A particular focus of the study was language skills in people with MWS. The findings were:
Around one-third of the group could speak at least one word, with the average age at which speech began being 4 years and 4 months. Two people with MWS in the study were able to say at least 200 words.
Some people with MWS were able to use augmented communication, such as sign language, picture cards or electronic communication devices. Other non-verbal methods of communicating included eye-gaze or body movements.
As a group, the people with MWS in the study showed slightly better receptive language (that is, their understanding of what others say to them) than expressive language (that is, their ability to express their own needs and wishes).
The main questionnaire used to assess behaviors in people with MWS was called the Developmental Behavior Checklist or DBC. The DBC consists of 95 items, each describing a particular behavior. Parents or carers were asked to rate whether the behavior never occurred or was never a problem for the person with MWS, whether it sometime occurred or was somewhat of a problem, or whether it occurred often or was a big problem. Only the DBC questionnaires for those MWS participants aged over 3 ½ years were used. This was 61 participants.
The questionnaires gathered from the MWS group were then compared with questionnaires which had already been collected in a large Australian study of children and adults with intellectual disability from varying causes (we have called this group of questionnaires the “non-MWS group”). The questionnaires selected for comparison were chosen in order to match the two groups as closely as possible for both age and level of intellectual disability. By doing this, we were able to find out which behaviors were more or less common in MWS compared with people of a similar age and with a similar level of development.
Overall, the results of the study suggested that there is a set of behaviors associated with MWS, both in terms of behaviors which are more common in people with MWS compared with people of a similar age and with similar levels of ID, as well as particular behaviors which are less common in those with MWS.
The behaviors in question can be categorized into 5 broad categories:
- Affect: Compared with the non-MWS group, people with MWS appeared to be happier. They were less likely to “appear depressed, downcast or unhappy”, or to “cry easily for no reason”. These findings are consistent with previous reports in the genetic literature suggesting that individuals with MWS typically display a happy affect, with frequent smiling. During the interviews and assessments, many participants also were noted to show a happy demeanor, with frequent smiling, and during the parent interviews, the topics of “happiness and smiling” came up often.
- Sociability: Compared with the non-MWS group, people with MWS were found to be more socially oriented and affectionate. They were less likely to “not show affection or to “prefer to do things on his/her own, tending to be a loner”. They were also more likely to “stand too close to others”. Taken together, these results provide some support for the anecdotal reports in the genetic literature that people with MWS display a sociable demeanor. The study also included a measure of temperament (the EAS Temperament Scale) and the findings from this scale are in keeping with the results of the DBC. In particular, the MWS scored higher than the non-MWS group for the Sociability scale of the EAS, and lower on the Shyness scale, and this is consistent with the MWS group’s lower scores on the DBC scale measuring problems in social relating. These findings are also consistent with the finding that many individuals with MWS display a strength in social skills.
- Oral behaviors: The MWS group showed a very high incidence of oral behaviors. They were more likely to “grind their teeth” (87% of the MWS group said this occurred sometimes or often) and to “Chew or mouth objects or body parts” (95% of the MWS group said this occurred sometimes or often). When parents and carers were asked to list other features which they thought could have been related to MWS, a number of respondents mentioned unusual dental characteristics. Furthermore, in the parent and carer interviews, dental anomalies such as missing teeth or having extra teeth were frequently mentioned. Another topic frequently discussed during interviews was drooling, which is not explored by the DBC. Overall, from both the unstructured and quantitative results, it would appear that oral behaviors are very persistent in MWS, even at older ages. However, during the unstructured interviews, some parents or carers of older MWS participants did report a decrease in chewing and mouthing objects in response to behavioral interventions (generally consisting of parents or carers saying “no” and/or removing the object from the person’s mouth).
- Stereotyped or repetitive behaviors: the MWS group scored higher for the items “flicks taps twirls objects” and “switches lights on and off or similar repetitive activity”. People with intellectual disability are more likely to show repetitive or stereotyped behaviors than the general population, and especially those with more severe disabilities. The results of the MWS study suggest a high prevalence of particular stereotyped or repetitive behaviors in MWS, even above that seen in others with a similar level of ID and of comparable age. The parent and carer interviews data gave further information about specific types of repetitive behaviors common in individuals with MWS. The most often mentioned was related to paper flipping, followed by switching lights on and off, and flicking or spinning objects.
- Under-reaction to pain: The MWS group were also more likely to show an under-reaction to pain. This finding was also supported by the many reports collected during the unstructured interviews, in which respondents reported a reduced or almost absent pain reaction to situations where one would be expected. Some of these reports included very painful situations such as broken bones.
Overall levels of behavior problems
We know from previous research that levels of behavioral and emotional disturbance are much higher in people with intellectual disability than in the general population. The results of the MWS study suggest that the levels of overall behavior problems in people with MWS is comparable to that of others of a similar age and with a similar level of ID. So although many people with MWS may have a happy, affectionate demeanor, it is certainly not true that they are always placid or easygoing. Those with MWS are just as likely to show behavioral problems as others with comparable ages and levels of ID, and over 30% of the MWS group were above the clinical cut-off of the Developmental Behavior Checklist, suggesting that over 30% of people with MWS may have clinically significant levels of behavioral and emotional difficulties. So even though many people with MWS show a happy, affectionate demeanor, it’s still important to address behavioral and emotional problems where they arise.
The study investigated whether people with MWS displayed the types of behaviors typically seen in people with autism. The behaviors typically associated with autism can be classified into three groups: problems of communication, problems of social interaction, and repetitive or stereotyped behaviors. However, repetitive or stereotyped behaviors are also common in people with severe intellectual disabilities without autism.
As a group, the people with MWS in the study displayed high rates of repetitive or stereotyped behaviors, but few problems of social interaction. Despite this, it would still be important for any person with MWS suspected of having autism to have full diagnostic assessment, since it is still possible that some people with MWS may meet the criteria for autism.
Growth physical health
Below is a summary of the findings from this study regarding growth and physical health in MWS. Because the purpose of this study was to collect information regarding behaviors and development, and it did not include medical assessments, these figures are based on questionnaire-reports only. More detailed information about the health conditions associated with MWS which have been based on medical assessments can be found in Garavelli and Cerruti-Mainardi (2007)’s review of Mowat Wilson syndrome in the Orphanet Journal of Rare Diseases.
It can be downloaded for free from: http://www.ojrd.com/content/pdf/1750-1172-2-42.pdf
Growth (height, weight, and head circumference)
Most people with MWS are born with growth measurements in the normal range, but as they grow, they may develop microcephaly (a small head) and short stature.
A substantial portion of the MWS participants were underweight for their height, based on their parents’ or carers’ reports of their height and weight. This may relate to other medical conditions associated with MWS such as Hirschsprung disease. In the interviews, some parents and carers mentioned feeding difficulties and this would also likely contribute to low body weight. The most common feeding difficulties mentioned were inadequate chewing, gagging on food, problems swallowing, and fussy eating. Some people were reported to show no interest in food or to be unaware of hunger and thirst cues. Three reported gastroesophageal reflux as being a problem. Seizures are known to contribute to feeding and nutrition problems in children without MWS, so it is also possible that this contributes to low weight in this group. The high rate of underweight in the group suggests that a nutrition intake assessment should be considered routine for individuals with MWS.
Health conditions known to be associated with MWS:
Almost ¼ of the group had ear or hearing problems, with most of this being ear infections and/or mild hearing loss.
57% of the group had eye problems or vision problems, but most of this related to strabismus (a turn in one or both eyes). 48% of the group had strabismus.
81% of the group had seizures or had suffered them in the past. Those who did not have seizures tended to do slightly better in terms of communication and daily living skills, and in terms of overall levels of adaptive behavior. However, there was no difference between those with and without seizures in terms of behavior problems. Several of the parents or carers of older people with MWS in the study reported that seizures improved after puberty.
In the unstructured interviews, the topic of dental anomalies was mentioned by 9 families.
There was a very high rate of sleep disorders in the group who completed the sleep questionnaire. The most common type of sleep disorder was Sleep-Wake Transition Disorders, which are classified as “parasomnias” (that is, things which intrude into the sleep process rather than being disorders of sleep or wake states). However, during parent and carer interviews, the most commonly described sleep problems were early morning waking and frequent night waking, both of which are “dyssomnias” (that is they are disorders that cause difficulty initiating or maintaining sleep). It may be that these types of sleep problems are more easily noticed by parents and carers, or perhaps that these problems are more obvious to families because they can cause disruption to the entire family’s sleep. One possible explanation for the high rates of sleep disturbance in MWS is that they may relate to the medical conditions associated with MWS, such as ear infections and epilepsy.
There were two pairs of siblings in the study, which suggests a recurrence rate of 2.9%. Recent estimates of the recurrence rate of MWS within the genetic literature have ranged from 1% to 2.3% so this is roughly the same as those estimates.
During the interviews, parents and carers were asked about other aspects of development and behaviors which were not covered by the questionnaires. Topics which came up often included sleep difficulties and feeding difficulties.
Eight people were reported to appear to lack confidence when walking alone – for example, they require someone to guide them, even though they are capable of balancing on their own.
Nine participants were said to have current problems of tactile defensiveness (that is, being overly sensitive to touch or showing an over-responsiveness to touch), and a further five reported that this had been a problem in the past. Tactile defensiveness was reported to create problems in learning fine motor skills, in learning sign language (due to the need to mould the child’s hands) and in skills such as dressing. Most who mentioned improvement reported using a “brushing” technique to desensitize parts of the body.
Poor fine motor skills were often noted during the assessments and interviews. Many children were noted to have a poor pincer grasp and to have difficulty holding things such as a pencil. It is possible that in some people with MWS, poor pincer grasp and poor fine motor skills may be related to eye and vision problems, especially strabismus (a turn in the eye).
A small number of parents and carers mentioned loss of previously acquired skills, but mostly this was following a bad seizure or another critical health event. When the scores for the assessments of development and of adaptive behavior were examined, it appeared overall that older people did display more skills than the younger ones, suggesting that people with MWS continue to develop over time.
Some parents mentioned that their son or daughter appeared to have low motivation to learn or to play. Others mentioned this as being a problem in the past, but not now.
Below is a list of recommendations to help in the care for people with MWS. This information is based on the results of the current study along with two recent reports in the literature (Mowat and Wilson 2010 and Adam et al 2006). As mentioned above, each person with MWS is an individual and so any intervention designed to enhance their medical care or quality of life must be tailored to their individual needs. An individual with MWS might have needs which are not listed here but are just as important as those needs known to be associated with MWS.
Attention to growth, an evaluation of feeding difficulties, a nutritional intake assessment. All people diagnosed with MWS should also be assessed for Hirschsprung disease and other intestinal problems.
Evaluation for eye problems by an ophthalmologist and treatment of any problems should be performed as early as practical.
As for all people with intellectual disability and communication difficulties, it is important to monitor changes in behavior, since these can be the first indication of an underlying medical complaint. A high proportion of people with MWS appear to display a reduced reaction to pain, and this can make it even more difficult to identify underlying problems. However, at this stage, we do not yet know whether the reduced reaction to pain is because they experience less pain or simply because they show it less. If they are in fact experiencing reduced levels of pain then they will need more supervision in learning to avoid potentially dangerous situations (such as hot or sharp objects).
It is important to screen for sleep problems in people with MWS and, where problems are identified, to consult a sleep specialist for more thorough evaluation of both sleep patterns and daytime sleepiness, as well as parasomnias and sleep-related breathing disorders. It is also important to distinguish between parasomnias and nocturnal seizures. An expanded EEG in overnight sleep studies can help here (Lee Chiong 2005).
A high number of people with MWS suffer from chronic ear infections. Where this is the case, a referral to an ear-nose & throat specialist may be helpful.
A person’s foot and ankle position should be examined and walking aids used where needed to encourage independent walking.
Medical management should include evaluation for, and management of seizures, cardiovascular monitoring and assessment for congenital heart disease, as well as assessment for renal problems and any urinogenital abnormalities.
Excessive mouthing and chewing of objects can cause damage to teeth and of course can increase the risk of choking or ingesting objects. Some parents of older people in the study reported improvement in mouthing behavior following repeatedly saying “no” and/or physically intervening to stop the person with MWS from biting or chewing objects. Behavioral interventions designed by psychologists and behavior therapists have proven helpful for people with intellectual disabilities from other causes and may be tried for people with MWS as well. Similarly, parents of children with developmental disabilities from other causes sometimes report that a helpful strategy is to provide a specially designed “chewy toy” which the child is allowed to chew and which is safe for his or her teeth and large enough not to be swallowed or inhaled. This strategy could also be tried for people with MWS.
Some parents in the study also reported success in teaching their son or daughter to wipe away drool using sweat bands or bandanas, or by repeatedly reminding them to swallow.
As for any condition known to be associated with developmental delay, early intervention to enhance development, and monitoring of development, are important for people with MWS. Early intervention should be commenced as young as possible.
Because many people with MWS have a better understanding of language but are less able to express things for themselves, an augmented communication system (such a picture exchange cards, a voice-output device, or sign language) could be very beneficial. Indeed, some participants in the study did use augmented communication systems to express their needs and wishes. Enhancing a person’s capacity to communicate can also be helpful in preventing behavioral problems. A psychologist or speech therapist who is experienced in working with people with an intellectual disability can provide guidance regarding how to implement an augmented communication system such as Functional Communication Training.
However, some parents and carers mentioned potential barriers when attempting to teach an augmented communication system. One such barrier was that sensory characteristics and behaviors frequently interfered with the teaching of the new skills – for example, if the person with MWS had sensitive hands and wanted to pull them away every time that a sign was being taught, or if they enjoyed chewing the picture exchange cards so much that the cards had to be taken away from them. This means that implementing communication systems with people with MWS may require tailoring the type of augmented communication system to the individual, with consideration of the types of behavior displayed. For example, for a person who likes to flip and chew paper, it may be more effective to use picture plaques which are on plastic or wooden boards (and thus at least less likely to be destroyed), or to attempt to teach simple sign language instead. Likewise, a child with overly sensitive hands may find more success with a communication device than with sign language.
Publication of results
We are currently preparing several formal publications based on these results and we plan to publish these in medical and genetics journals over the next year.
Establishing a MWS clinic
Dr. Mowat has begun a MWS clinic at Sydney Children’s Hospital which we hope to expand in 2011. The aim of the clinic is to provide advice and follow-up for individuals with MWS. The clinic involves a multi-disciplinary team including geneticists (Drs. Mowat and Wilson), as well as psychologist (Liz), pediatric neurologist, pediatric gastrointestinal surgeon, and there are plans to add further allied health professionals such as a speech pathologist, occupational therapist, and physiotherapist.
Liz Evans has written a 400-page PhD thesis based on this study and will graduate later this year. She is now working at the University of New South Wales in their new Department of Developmental Disability Neuropsychiatry. Although her main task there is a study focused on ageing in people with disabilities, her interest in rare genetic syndromes, and particularly MWS, continues. Liz can be contacted on firstname.lastname@example.org.
Dr. Mowat is still working at the Department of Medical Genetics at Sydney Children’s Hospital. Dr. Wilson is still working at the Children’s Hospital at Westmead and, like Dr. Mowat, continues to be involved in both clinical and research work on MWS. He has recently been involved in an Australian research project looking at seizures in people with MWS. The other person working on that project is Dr. Gabriel Dabsheck.
Dr. Meredith Wilson is the Head of the Department of Clinical Genetics at the Children’s Hospital at Westmead, where she is involved in clinical consultations, as well as being engaged in research on several genetic syndromes, including MWS.
Professor Einfeld is now the Chair of Mental Health in the Faculty of Health Sciences at Sydney University, as well as being a Senior Scientist at the Brain and Mind Research Institute.