1. d i s a b i l i t y a n d r e h a b i l i t a t i o n , 2001 ; v o l . 23, n o . 3}4, 118 128Growth and nutrition in Rett syndrome SHEENA REILLY and HILARY CASS Faculty of Health Sciences, La Trobe University and the Royal Childrens Hospital, Melbourne, Australia Great Ormond Street Hospital London, UKAbstract Purpose}Method : In this paper we review the existing literature on factors that contribute to growth failure in Rett syndrome (RS) with particular emphasis on the extent and nature of the feeding di culties that arise. Data on growth and feeding related problems, collected over four years in a specialized clinic for females with Rett syndrome are presented and management protocols developed in the clinic discussed. Results}Conclusion : Feeding related problems and growth failure occur commonly in Rett syndrome yet our understanding of the mechanisms causing growth failure are poorly understood. Both nutritional and non-nutritional factors are thought to contribute and it has not been possible to develop e cacious intervention strategies. Consequently, clinical management of growth failure in Rett syndrome is not evidence based.Introduction Rett Syndrome (RS) is diagnosed by observation and clinical assessment using the criteria developed by the Rett Syndrome Diagnostic Criteria Work Group." Despite the recent discovery of the role of the MeCP2 gene in RS,# it is too early to know what proportion of cases is attributable to this gene anomaly ; thus clinical diagnosis is still essential. Although the necessary diagnostic criteria are well recognized, a number of supportive criteria also exist which include mention of feeding problems and growth retardation. However these tend to be less well recognized and are therefore often neglected aspects of clinical care in RS. In this paper we will discuss the factors that contribute to growth failure in RS with particular emphasis on the extent and nature of the feeding di culties that commonly arise. Data from 4 years experience in a multidisciplinary Rett Therapy Clinic in the UK will be presented followed by two case histories which will illustrate the multiple and complex basis of growth failure in this population. We also outline the dysphagia protocols developed in the clinic and their importance in monitoring growth and feeding in RS. * Author for correspondence ; e-mail : s.reilly!latrobe.edu.auf a c t o r s c o n t r ib u t in g t o g r o w t h f a il u r e in r e t t sy n d r o m e The aetiology of growth retardation in RS is complex. Whilst somatic growth retardation has been well documented, many females meet the criteria for moderate to severe malnutrition.$ Unfortunately, there has been limited discussion of the many factors which either individually or in combination might a growth in ect RS. The exception is the widely discussed deceleration in head growth. Schultz et al. noted that deceleration of head growth, followed by deceleration of weight and height measurements begins as early as 3 months of age and persists throughout childhood.% They concluded that this pattern of growth might provide the earliest clinical indicator for the diagnosis of RS. Thomessan and colleagues & described similar ndings with a fall oin linear growth in the rst few years of life ; none of the girls studied had height or weight for height above the 2nd centile. Leonard et al. recorded weight and height in 51 girls aged between 3 and 16 years and calculated a Quetelet Body Mass Index. Girls diagnosed as having classical RS were found to have lower mean BMI (SD : 1.96) than girls with atypical RS (SD : 0.83). What factors might account for these poor growth patterns ? Both nutritional and non-nutritiona l (sex, age, disease severity, cognitive impairment and ambulatory status) factors contribute to growth failure in children with similar levels of physical disability (e.g. cerebral palsy) and it is likely that similar mechanisms will apply in RS. Nutritional problems may result from abnormalities of the digestive tract, leading to dysphagia and thus to reduced intake. Additionally alterations in energy balance may exacerbate reduced calorie intake. The clinical basis for these suggestions will be reviewed in turn. Abnormalities of the digestive tract Gastrointestinal problems in RS may occur at any stage from preparation of food within the oral cavity (theDisability and Rehabilitatio n ISSN 0963 8288 print}ISSN 1464 5165 online # 2001 Taylor & Francis Ltd http :}}www.tandf.co.uk}journals

2. Growth and nutrition in Rett syndrome Table 1 Feeding problems in 60 females with RS) Oral stage : oral motor dysfunction Oral-pharyngeal stage Oesophageal stage(n (n (n 25) 12) 9)41 % 20 % 15 %oral phase) to elimination. In Rett syndrome, disruption of swallowing may occur at any stage causing signi cant impairment of the eating and drinking process and resulting in dysphagia. Throughout this paper the term `dysphagia will be used to describe disorders of swallowing that may occur in the oral, pharyngeal or oesophageal stage. The consequences of dysphagia for both females with Rett syndrome and their carers are widespread and a general health, development and ect well being. In addition, such problems create an additional burden for the family. For example, carers may need to spend inordinate amounts of time feeding their child. Oral and pharyngeal function Although feeding has been reported as problematic in RS by a number of researchers,( "! there have been no systematic studies of the exact nature of these di culties. The existing studies should be interpreted with caution as they usually involve small clinical or volunteer samples. Budden( described abnormal chewing associated with tongue thrusting and involuntary, undulating tongue movements in 11 of the 13 girls she studied. Feeding problems were characterized by di culty chewing and swallowing foods with associated coughing and regurgitation. In a later series of 20 girls who ranged in age from 3 years 11 months to 19 years 4 months, Budden and colleagues) related oral motor function to the four main stages associated with RS (see Ellaway and Christodoulou, this issue). Changes in oral motor tone, from hypotonicity in stages I and III to hypertonicity in stage IV, were reported. Altered oral tonicity was thought to be directly related to postural tone, which presumably also changed with progression through the four stages. Tongue deviation (to the left) was noted in almost all females in stages III and IV and three girls in stage IV also showed fasiculation of the tongue both at rest and during active movement. Nineteen of the girls were fed orally (one child was fed by gastrostomy tube), but all required a diet of soft or pureed foods because of the di culties they experienced chewing food e ectively. More recently Budden"" described a much larger clinical series of 60 individuals with RS with particular emphasis on the management of feeding di culties, communi-cation needs, hand function, scoliosis and deformities. Feeding problems were reported in 82 % of the cases seen in the clinic (n 49) and the data is classi ed in table 1. Oesophageal problems in this group usually refer to gastro-oesophagea l re ux or the spontaneous return of the gastric contents into the oesophagus. Gastric contents may be re uxed into the pharynx and cause regurgitation and}or vomiting. Nine of the girls (15 % ) were being fed by gastrostomy, the reasons given included severe gastro-oesophagea l re ux (n 5), swallowing problems (n 2) and growth failure in the absence of oral motor and }or oral pharyngeal dysfunction (n 2). Witt-Engerstrom"! described similar di culties, but also commented on the presence of profuse drooling and an inability to close the mouth during swallowing. Morton and colleagues* used a di erent approach and classi cation system to study feeding di culties in 20 females with RS who presented to a specialist-feeding clinic because their carers were concerned about feeding problems. The subjects, aged between 1.5 and 33 years, were classi ed according to muscle tone subtypes as described by Kerr."# These subtypes are : subtype 1 predominant hypotonia, non-ambulant, young ; subtype 2 normal tone, ambulant ; subtype 3 dystonia, mainly ambulant ; and subtype 4 marked rigidity with xed deformities, non ambulant. As well as taking a detailed feeding history and performing a clinical examination, a mealtime was observed in the clinic and video uroscopic examination of the swallow performed. This involved the administration of both a liquid and solid texture (Weetabix impregnated with barium) being fed to each individual in the x-ray department. Numerous ratings were made of di erent aspects of feeding including the carers reports of di culties, oral and pharyngeal function during video uroscopy and chewing scores. Not surprisingly all carers reported some degree of di culty with feeding ; in nine individuals this was reported to be mild, de ned as the main meal taking less than 15 minutes with food requiring some modi cation (e.g. solids foods required mashing). Six carers reported that the problems were moderate (mealtimes taking between 15 and 30 minutes) and ve carers said the problems were severe (mealtimes taking more than 30 minutes). An interesting nding in this study was that three of the females (aged 4, 6 and 23 years) had con rmed aspiration on video uroscopy. These subjects also scored the highest on frequency of chest infections (more than three chest infections requiring antibiotics in the past 12 months) and were rated as being most di cult to feed on the carer s di culty scale. In contrast, no other individual 119 3. S. Reilly and H. Cass was aspirating nor did they experience such frequent chest infections requiring antibiotics. There were a number of other indices which suggest that these three subjects were in the most severe range, including the fact that they were all non-ambulant and tended to be amongst the most poorly grown in the sample (weight for height as a percentage of the 50th centile for age ranged from 45 to 74). As well as reporting detailed data regarding speci c aspects of oral and pharyngeal function, Morton and colleagues * suggest that their results are indicative of regression in oral skills leading to increased impairment of chewing ability in older females. In a separate study the same authors found that the time taken to swallow appeared to increase with age."$ Oesophageal function The prevalence of gastro-oesophagea l re ux (GOR) in girls with RS is unknown, although it is mentioned as problematic by a number of authors. Witt-Engerstrom"! reported that vomiting was common, particularly in those girls in stage three. Fifteen percent of girls in the sample described by Budden"" had gastro-oesophagea l re ux, although it is not clear if this had been con rmed by investigation or on the basis of clinical symptomatology. Bowel function Constipation is one of the most commonly presenting clinical problems which may a as many as 85 % of ect females,"% but is not thought to be associated with neuronal dropout in the colon."& Presumably the causes of constipation in RS are multi-factorial (e.g. lack of physical activity, poor muscle tone, diet, drugs, inadequate liquid intake, scoliosis etc.) as is the case with other children with multiple and complex disabilities. Reduced intake In one of the few studies to date to examine actual intake, Thommessen and colleagues& found that the mean energy intake of the girls (n 10) they studied was 66.9 % of the US recommendations according to age and 107.8 % of the recommendations according to body weight. Intakes of thiamin, vitamin D, calcium and iron were also considered low but none were found to be anaemic. These feeding problems have serious consequences for childrens growth, their nutrition and physical health (including bone quality), and for the psychological well being of parents. Only 13 % of RS cases did not show some radiological evidence of 120osteopenia ; the incidence of fractures would appear to be signi cantly higher than in the general population. Alterations in energy balance Clinicians have hypothesized that alterations in energy balance might account for growth failure in RS girls. Many girls reputedly have large, healthy appetites yet remain malnourished. In addition, behaviours such as repetitive hand stereotypies, rocking motions of the upper body and breathing irregularities occur commonly ; in one study 66 % of parents said their daughter had unusual breathing ; 44 % described hyperventilation and breath holding, 34 % hyperventilation alone and 17 % breath holding alone. These behaviours were more common in girls with classical RS compared to atypical RS. Constant hand wringing and hand to mouth activity (which can persist in some girls throughout their waking hours) can be particularly problematic causing skin excoriation. Motil and colleagues" "( carried out two studies in an attempt to better understand metabolic rates in RS. In the rst they found that metabolic rates while sleeping and quietly awake, were lower (by 23 % ) in RS girls as compared to healthy controls, although metabolic rates while actively awake did not di between the groups. er However, because of the 2.4-fold greater time spent in involuntary motor movement, energy expenditure associated with activity was twofold greater in RS girls than in controls. Although total daily energy expenditure of the two groups did not di signi cantly, energy balance er was less positive in RS girls than in the controls. The authors concluded that this small di erence in energy balance, if sustained over months to years, might be su cient to account for growth failure in RS. However, in the second study Motil et al. (1998 ) found that increased total daily energy expenditure (TDEE) did not di signi cantly between girls with RS and healthy er girls. "( Despite the fact that girls with RS spent more waking hours in physical activity than their healthy counterparts (85 % 10 % vs 73 % 11 % awake time per day), their repetitive movements were not su ciently intense to increase TDEE. Lean body mass, but not body fat, was signi cantly less in girls with RS, which Motil and colleagues thought contributed to their lower absolute TDEE in comparison with that of healthy girls (845 251 vs 1453 534 kcal}day). In contrast, a number of interesting factors emerged from a recent study which found that the presence of a breathing disorder and ambulatory status (whether the child had walked or not) a ected BMI whereas level of feeding skill and hand stereotypy did not. When these 4. Growth and nutrition in Rett syndrome three variables were all included in a multivariate analysis, each remained independently signi cant. There are a number of problems in interpreting the existing studies which have attempted to investigate altered energy balance as a possible cause for growth failure in RS. First the studies have compared females with RS to healthy, able-bodied controls. It is not surprising that no di erences were found, as the activity levels in a profoundly and multiply handicapped girl with RS must be qualitatively di erent from a healthy active control. However, would they di from other er females with equally profound physical and cognitive impairment ? Second, adequate measures of activity levels in RS have not been made. In the main, researchers have relied on parental descriptions and questionnaires and occasionally, observational techniques have been used. Third, the full range of activity or behaviour that might occur (e.g. respiratory irregularities, hand stereotypies, body movements, ambulatory status) has also not been taken into account.d a t a f r o ma m u l t i -d i s c i p l i n a r y c l i n i cWe have highlighted some of the multiple and complex problems relating to feeding and nutrition in RS. There is no doubt that these problems require the skills of many di erent professionals both for assessment and management advice. In addition, because RS is a low prevalence condition, there is almost inevitably limited expertise available in the community. Internationally, a multi-disciplinary team model has been recommended and adopted as the ideal method for managing the multiple, complex and often interrelated issues (e.g. nutritional, orthopaedic, neurological, behavioural ) that arise in RS. A number of teams spread around the globe (e.g. Sweden, USA) are now well known for the multidisciplinary nature of their work. With these considerations in mind, the authors together with their colleagues started a Rett Therapy Clinic based within a diagnostic and assessment unit just outside London in the UK. The Rett Clinic team consisted of a music therapist, speech and language therapist, occupational therapist, physiotherapist and paediatrician, all of whom have previously worked individually with patients with Rett syndrome, in a clinical and}or a research capacity. The clinic followed a consistent format, but the procedures were dictated to a large extent by the individual girls needs and the questions posed by their carers}families. Each session began with an interview to elicit medical background, con rm diagnosis (if necessary ) and identifyTable 2Sample characteristics Number ( % )Scoliosis identi ed Type Mobile scoliosis Fixed scoliosis Epilepsy* Mobility rating Independent** Assisted walking Immobile Self-feeding Independent*** Assisted Dependent Cognitive function Make a choice" Eye point# Speech$51 (86 .4) 20 (33 .9) 31 (52. 5) 37 (62. 7) 20 (37 .3) 18 (30 .5) 21 (35 .5) 2 (3.4) 22 (37 .3) 35 (59 .3) 30 (50 .8) 40 (67 .8) 8 (13 .6)* De nite evidence of seizure activity. ** The ability to walk without assistance. *** Can self feed with either ngers or a utensil such as a spoon " The ability to select food, desired object etc. from array presented (usually from no more than two). # Uses eyes, eye gaze to indicate what is wanted, get attention etc. $ Uses words (in the majority of subjects, single word use) but not necessarily in context.current management concerns. Concerns expressed by both the referrer and the families were recorded. As well as multi-disciplinary assessment, the combination of therapists allowed for multi-disciplinary advice. A written report detailing team recommendations was sent to the family and other professionals involved. In addition, the assessment and discussion were video taped, and a copy made available to the parents. Local therapists were encouraged to attend the clinic with the family, but where this was not possible we attempted to follow up with telephone contact. Over a 5 year period, 100 females with a diagnosis of RS were referred to the clinic. The main referral sources were family doctors (49.2 % ) and paediatricians (44.1 % ). In a retrospective, descriptive study we explored feeding di culties in a sub-sample of 59 females aged between 2 years 1 month and 44 years and 9 months (Mean : 12.6 years SD 11.04 years). Information about growth (e.g. weight and height), nutrition (e.g. appetite, dietary intake), feeding ability (e.g. oral, pharyngeal and oesophageal control), feeding dependency (e.g. ability to self-feed) and other feeding related issues (e.g. constipation, respiration ) was systematically recorded on a subset of females attending the clinic during an 18 month period. The sample characteristics shown in table 2 indicate 121 5. S. Reilly and H. CassCumulative number of impairmentsSum of impairments 526420382411 051015 Proportion202530Figure 1 Sum of impairments (epilepsy, immobility, feeding dependency and scoliosis).the multiple and complex nature of the impairments found in RS. Eighty-six percent of the females had a scoliosis (either xed or mobile) and 62 .7 % had epilepsy. Although 37.3 % of the girls were rated as independently mobile, this does not imply that they were able to walk long distances or cope on a variety of walking surfaces, rather that for daily activities they were able to move around the room or from room to room. Just two of the females were able to feed independently, one using a spoon and one with her ngers. All of the girls had profound cognitive impairments, the highest evidence of skill level being their ability to make choices, usually using eye gaze. Although some of the girls did have words and some used phrases and short sentences, there was little evidence that these were used in context. Instead the words, phrases and sentences appeared to be used out of context (this was con rmed by most parents) and sometimes in a repetitive fashion. We summed the main impairments (epilepsy, immobility, feeding dependency and scoliosis) and these results are shown in gure 1. These data show that 91.5 % of the sample had two or more impairments, which is indicative of the disabling nature of RS. During the initial interview parents were asked to identify their main problems in caring for their daughters. Just over half (52.5 % ) indicated that they were experiencing some feeding related di culty and 27 % had received some previous help with feeding problems. All of the girls were being fed orally and none had a history of non-oral feeding. Almost all (83 % ) were described as having an excellent appetite, a nding reported previously by other researchers.& Oral motor skills were assessed using the screening version of the Schedule for Oral Motor Assessment 122Figure 2 Weight (SD scores) for a subsample of girls (n correlated with age.27)(SOMA). "), "* The SOMA entails the standarized presentation of a variety of tastes and textures puree (e.g. ; yoghurt ) semi-solids (e.g. baked beans), solids (e.g. rm pieces of fruit or potato ) and liquids (drinking from a cup). Ratings, made subsequently from video recordings, enabled the categorization of oral-motor function as normal, or as abnormal. A total abnormality score summed across each of the four textures was computed. Scoring decisions are fully explained in the SOMA scoring manual#! and in previous publications."), "* Twenty-one females (36 % ) had either no oral motor problems or mild impairment and were able to manage a normal adult diet containing a range of tastes and textures. Those with mild oral motor impairment required some monitoring of their diet usually because they had di cult managing foods which required chewing such as meat or an apple, although they may have been able to manage these textures if the food was nely chopped or specially prepared. Thirty eight females (64 % ) had moderate to severe oral motor dysfunction as indicated by SOMA. These di culties resulted in an inability to manage a full diet and, for some, subsistence on a liquid or smooth, pureed diet. Such severe oral motor impairment has been shown to contribute to a compromised nutritional intake and subsequent growth failure in children with similar levels of di culty such as cerebral palsy. We analysed anthropometri c data from 27 of the subjects aged between 3 and 16 years. Of the remaining cases 16 were females older than 16 years of age and we had incomplete and unreliable data on the remaining 16 subjects who were therefore not included in the analysis. 6. Growth and nutrition in Rett syndrome The mean weight of the group (n 27) was 2.98 standard deviations below the population mean (SD 3.9 range 13.86 3.53). Of these, 26 % were classi ed as severely malnourished with weight more than 4 standard deviations below the population mean (range : 4 to 15 standard deviations). There was a signi cant correlation between age and weight : the older girls were steadily falling away from the population mean and subsequently growing very poorly (see gure 2). Interestingly, none of the younger girls (less than 4 years of age) were more than 2 standard deviations below the population mean (n 7) suggesting that girls with RS are more likely to fail to thrive as they grow older. However, unlike cerebral palsy where a direct correlation between the severity of the oral motor de cit and growth outcome was identi ed, in RS there was no such correlation. #" That is, some girls with normal oral motor control were also growing very poorly.c a s e h is t o r ie s Patricia Patricia aged 30 years, was referred to the Rett Clinic because of concerns abut the management of her epilepsy, mood swings, posture and severe constipation. She was totally dependent, requiring 24 hour support from a team of care workers. Feeding was not considered problematic by Patricia s carers or her parents. Appetite was said to have decreased recently and this was thought to be related to her mood swings and emotional behaviour and constipation. During the preceding 12 months Patricia had refused to eat on two occasions for up to 7 days, but did continue to drink during this time. Her carers did attempt to supplement her intake with a number of liquid dietary supplements with mixed success. Although Patricia almost always ate breakfast and lunch she inevitably refused an evening meal. She drank from an adapted cup or from a straw. Patricia s mood swings were thought to be associated with pain and discomfort on being moved or manipulated, seating posture and constipation. Bowel management consisted of lactulose (15 ml twice daily), Fybogel and suppositories as required. Patricia s general health was reportedly good with no increase in upper respiratory tract infections. Recent blood tests were normal. Patricias other medications included an anticonvulsant (cabamazepine 400 mg mane, 200 mg nocte) although she had been t free since the age of 14. She had also been taking baclofen for several years. Physical examination was di cult and limited due to Patricias marked asymmetrical posture both in lyingand in sitting, such that when placed in supine she was unable to conform to the surface of the bed. She was known to experience acute pain on handling and was found to have a dislocated left hip with xed contractures at the right hip, knees and ankles. During the examination it became clear that Patricia was very underweight. However, we were unable to accurately weigh and measure her because of her extreme discomfort, and the severity of her contractures made any estimate of linear growth impossible. We did however obtain information from Patricias records over the preceding year, which indicated a steady weight loss amounting to 12 kilograms over a period of 9 months. Two long-standing pressure areas were noted on her left and right foot as well as more recent reddened broken area on the left elbow and left shoulder. Patricia had been provided with some adaptive seating, but her asymmetry in sitting was such that if she was sat with her head balanced over her shoulder girdle, she was in fact looking to her left due to the extent of her forward rotation. As a result she spent the majority of her time in sitting turning to look over her right shoulder in order to maintain forward gaze. Patricia was in a poor nutritional state. Her steady weight loss over a period of 9 months was of grave concern. In the short term we recommended an urgent referral to a dietician for advice regarding immediate nutritional supplementation via high-energy supplements. We also discussed with Patricia s carers the need to consider supplementary tube feeding (either by n}g tube in the short term or gastrostom y in the long term) if she continued to loose weight despite supplementation. A number of other recommendations regarding management of Patricias constipation were also made including abdominal massage and regular sitting on the toilet. Patricia s pressure sores and pressure areas required immediate management and regular monitoring by her family doctor. There was some follow through of the recommendations made, particularly those relating to management of the constipation. However, Patricia continued to lose weight and 5 months later was admitted to hospital with reduced appetite, bedsores, cellulitis and oral candida with refusal to both eat and drink. Endoscopy was performed and she was found to have gastritis for which treatment was instigated. Gastrostomy feeding was strongly recommended by the investigating medical team. A telephone follow-up revealed that Patricia did eventually have a gastrostomy inserted and her parents were very pleased with the outcome. She continues to feed orally and receives supplementary feeds via her gastrostomy. She is reported to be in excellent health and 123 7. S. Reilly and H. Cass has had no further recurrence of pressure sores or pressure areas. Sally Sally, aged 25 months, had only recently been diagnosed as having RS and her parents were concerned to gather as much information as possible about her likely future development. She was referred to the Rett Clinic because of concerns regarding her feeding, seating and development of her hand skills. Her general health was good and she has not had any major illnesses. Seizures began at 10 months, mostly with fever, but she had never received anticonvulsants and had not had any seizures for the past 3 months. When rst seen Sally was eating a specially prepared diet of nely chopped foods and was unable to chew meats or manage dry foods. She tended to store food in her mouth and often choked on lumpy foods. Sally dribbled profusely and would lose a considerable amount of food when eating and liquid when drinking. Mealtimes were prolonged, taking up to 90 minutes, depending on the food texture and the number of coughing and choking episodes. Vomiting occurred occasionally but was not felt to be problematic. Food and liquid were often nasally regurgitated and Sallys parents felt this had worsened recently. Sally gained weight slowly (over the previous 12 14 months she has gained just 1.6 kgs) and at times had lost weight. She had been referred to a dietician for advice, but was not taking any supplements. She was said to have an excellent appetite and to communicate hunger by making a particular noise. Sallys mother commented that she found it di cult to know when she was satiated, as she always seemed hungry. Sally was not ambulant but could sit independently both on the oor and on a stool. Her posture was kyphotic and a postural scoliosis was already evident as well as shoulder protraction and elevation. She spent much of her time either mouthing, clasping or wringing her hands. Her weight was 9.5 kgs at 24 months (! 3rd centile). Sally was able to manage purees and semi-solids (soft lumps). Although she had a good range of oral motor movements (e.g. lateral tongue and lateral and rotary jaw movements ) these were very poorly integrated and she was unable to chew food. She breathed through her mouth, which caused some incoordination especially when drinking. Sally s posture when eating and drinking was unstable. Sally was in a reasonable nutritional state but her weight had fallen below the third centile and required monitoring. We recommended that Sally should see a 124dietician regularly and that supplements be added to her diet. We also recommended that the frequency of vomiting and nasal regurgitation be kept under review and investigations for possible gastro-oesophagea l re ux be undertaken if necessary. A seating review was instigated to develop stability and provide a good working base for eating and playing. Sally was seen again for a review appointment at the request of her parents when aged 4 years and 11 months. They were concerned at her poor weight gain, the prolonged duration of her mealtimes, frequent eye infections and increasing discomfort when eating and drinking. Sally had recurrent super cial eye infections (blepharitis and a series of cystic lesions on the external lid margins) which her parents thought started after an episode of herpes stomatitis. She had also su ered from occasional fevers with no clear focus. Although she had had no chest infections she was said to sound increasingly `chesty with excessive secretions in the pharyngeal area and production of thick frothy mucous. No increase in vomiting or regurgitation was reported but the family did take elaborate precautions to carefully position Sally after meals. Sally was said to tense up in pain in a foetal position for periods of up to 20 minutes and appear to be distressed ; these were sometimes associated with mealtimes and increased hand to mouth activity. Mealtimes continued to be prolonged (60 minutes). Despite supplementation Sallys weight was 12.7 kg s, indicating a gain of just 3.2 kg s in almost 3 years. Although Sally had been provided with dietary supplementation no health professional had continued to monitor her growth during this time. Her nutritional state on examination was poor and this was thought to be the most likely cause of her recurrent eye infections. It became clear that Sally might well have gastro-oesophageal re ux, which had unfortunately not been investigated despite our earlier recommendations. In the short term we recommended that 24 pH monitoring be undertaken as well as some baseline blood tests to check immune function, blood count and other indices of nutritional status. We discussed with Sally s parents the need to consider supplementary tube feeding (either by n}g tube in the short term or gastrostomy in the long term) if she continued to fail to gain weight satisfactorily despite supplementation. Telephone follow-up revealed that because Sally continued to loose weight and experience frequent chest infections, a gastrostomy was inserted, although she also continued to feed orally. Positive health outcomes were reported by her parents. Sally had rapidly and steadily gained weight and she had not had any further chest or eye infections. 8. Growth and nutrition in Rett syndromeFigure 3Multi-factorial nature of feeding problems in RS.g u id e l in e s f o r f e e d in g a n d n u t r it io n a l m a n a g e m e n t There are four principles for the successful management of feeding and nutritional problems in individuals with RS. These are based on the management of children with other motor problems such as cerebral palsy.## They include a comprehensive assessment, adopting a problem solving approach, assess and manage dysphagia within the context of the childs other problems and discuss and agree management regimes with parents}carers, other professionals. It is beyond the scope of this paper to discuss these principles in detail. They are, however, important as the problems that present in clinic are complex and they intersect a number of specialist areas and disciplines (e.g. orthopaedic surgeon, speech pathologist, physiotherapist). Furthermore, the management strategies adopted are almost always dependent on other aspects of the childs function (e.g. the relationship between oral motor function and postural control). Feeding Early identi cation and management of the complex feeding problems that present in females with RS is essential. However, there is some evidence of deterioration in growth#$ and evidence of change in oral motor skill level with increasing age.* This deterioration may well be linked to postural status, just as it is in other conditions such as cerebral palsy. There is no doubt that the aetiology of feeding problems in RS is complex and multi-factorial as illustrated in gure 3. All of these factors should be taken into account when managing females with RS across the age span.Figure 4 Decision-making : considering the safety and adequacy of oral feeding in RS.Where oropharyngea l skills are dysfunctional to such an extent that an individual is unable to safely achieve an adequate nutritional intake via oral means, alternative methods of feeding should be considered (see gure 4). Safe feeding presumes that the child is not at risk of aspiration or penetration of material into the airway during eating and drinking. In determining the safety of oral feeding information is collected from a number of sources including : EEEEECase history (e.g. history and frequency of chest infections), Medical examination (e.g. auscultation of the chest before, during and after feeding and examination of the respiratory system), Swallow investigations (e.g. video uroscopic examination of the swallow mechanism where indicated), Baseline investigations of the respiratory system (e.g. chest x-ray); and Further investigations of respiratory function (e.g. lung scans).For further information readers are referred to a recent publication, ## which details protocols for managing unsafe feeding. Indications for the instigation of nonoral feeding include: EEInability to consume adequate calories orally to meet energy requirements ; Evidence of ongoing aspiration during oral feeding ; 125 9. S. Reilly and H. Cass EEE EE EOral feeding is stressful for either the carer or the child or both ; Mealtimes are protracted leaving limited time for other daily activities ; Oral supplementation of the diet has failed ; Chronic food}liquid refusal or aversive behaviour has developed ; Oral intake is erratic; and A safe route for regular medication (e.g. anticonvulsants ) is required.Individuals with less severe oral and pharyngeal involvement may bene t from a variety of other therapeutic techniques such as, optimizing posture and seating, manipulation of texture, change of utensil, alteration of the pacing of feeding and advice regarding self-feeding. Health professionals need to be aware that gastrooesophageal re ux tends to occur more commonly in children with motor problems (for example, RS and cerebral palsy). Children with profound intellectual disability and motor problems cannot always alert their carers to the fact that they are in pain or uncomfortabl e and they will almost certainly not be able to isolate the source of pain. For these reasons, it is important to alert carers to the increased prevalence of GOR in RS and to inform them of any potential signs and symptoms that might indicate the presence of GOR. GOR may of course be present in the absence of any ongoing vomiting and regurgitation and therefore not readily identi ed. Management of GOR should be done in consultation with a paediatrician and}or gastroenterologist . A phased therapeutic approach to the management of GOR is usually recommended for children with motor problems.#% Three phases are outlined : in phase one attention is given to position, dietary advice and thickening agents. Traditionally thickening feeds and the maintenance of an upright position after feeds have been encouraged, however these are no longer thought to be e ective in children with neurological disorder. Medical management via the use of antacids, such as gaviscon, to neutralise the gastric acid and Sucralfate to protect the mucosa may be added. In phase two, prokinetic agents, such as cisapride, which aim to increase the tone of the lower oesophageal sphincter and enhance gastric emptying may also be added and H# receptor blockers and proton pump inhibitors may also be given for persistent problems. The outcome for medical management of GOR in children with neurological problems has been less rigorously evaluated but is known to be less e ective than in normal 126children. Surgical management (e.g. fundoplication ) may therefore need to be considered.Anthropometry The assessment of the nutritional status of the individual with RS serves as a guide to nutritional intervention. Routine and regular monitoring of growth parameters including weight, height (substitute measures, for example, lower leg measurements ) may be necessary in females with postural deformities and in those who have undergone spinal surgery. Routine monitoring should continue throughout the life span as illustrated by our case studies. Failure to do so may not only result in the presentation of an acute problem but results in no baseline data being available to assess individual growth patterns. This is essential, but too often absent, diagnostic information. Indicators for early nutritional intervention include : height-for-ag e and weight-for-height or -age Z-scores more than 2 SD below the mean for age, height-for-ag e measurements less than 95 % of expected, weight-for-height measurements less than 90 % or greater than 120 % of expected and height velocities less than 5 cm }year after 2 years of age.Nutritional supplementatio n Nutritional management of females with RS has been a neglected aspect of their care. In many cases it is clear that under nutrition contributes to poor growth. However, in RS there are other factors throughout to a growth ect outcome ; the mechanisms are not well understood. However, malnutrition is correctable. Nutritional therapy should be an integral part of the comprehensive care and rehabilitation aiming not only to improve weight and linear growth, but to improve physiological and functional capacity. Very little is known about the speci c nutrient requirements of individuals with RS. Caloric requirements are usually estimated from Recommended Daily Allowances (RDAs). However, RDAs assume normal levels of activity and are therefore not necessarily appropriate for children with complex and multiple disabilities. A variety of methods are used to calculate energy requirements in the child with complex and multiple disabilities and it is beyond the scope of this paper to review them. However, as a rule of thumb clinicians recommend that energy requirements be based on the RDA for height age or weight at the 25th percentile weight for height. Others recommend determining basal 10. Growth and nutrition in Rett syndrome metabolic rates which are corrected for activity levels, such as the World Health Organization (WHO 1985 ) formulas which allow for more individualized prediction based on gender, age and body weight as well as accounting for activity levels. Krick#& developed a factorial approach based on estimating resting energy expenditure needs, muscle tone alterations, normal growth needs and catch up growth or nutritional repletion in malnourished children. Whichever approach is used it is crucial that a paediatric dietician experienced in the management of children with multiple and complex needs be part of the team to evaluate and establish nutritional plans for each child. Monitoring these plans is of vital importance to ensure those children reach the expected growth targets. However, in the case of some children, particularly those children who are gastrostom y fed, it may be necessary to ensure that they do not exceed weight targets. For some females with RS the dietary intake can be supplemented naturally through the use of high energy and high bre foods. However, for others this is not possible and supplementation with commercial products is necessary. This should always be in consultation with and on the advice of an experienced paediatric dietician.Acknowledgements We would like to acknowledge the other members of the multidisciplinary Rett clinic team and the families and children. This work was supported by, and undertaken at Harper House Childrens Centre, Horizon NHS Trust, Radlett, Hertfordshire. United Kingdom.References 1 23 4 5 6 7 8 9Conclusions10The management of feeding problems and nutrition in RS is of great importance but it is also a challenge. Asaro # states that :11Nutrition represents one of the most important aspects of treatment in RS. It is the cornerstone by which all other forms of therapies are made possible.12 13 14 15The challenge is made harder by our limited knowledge about the many factors that contribute to growth failure and which of these are the most powerful predictors of growth failure. As a result it has not been possible to develop e cacious intervention strategies and many of the management strategies commonly used are not underpinned by evidence based practice. Despite this, guidelines for good practice have emerged from clinical practice and the small body of literature that exists regarding therapeutic management. The challenge for the future is to improve our understanding of the factors contributing to poor feeding and growth failure in RS, enabling clinicians and researchers to develop treatment regimes and assess the e cacy of these approaches.16 1718 19 20 21 22The Rett Syndrome Diagnostic Criteria Working Group. Diagnostic criteria for Rett Syndrome. Annals of Neurology 1988 ; 23 : 425 428. Amir RE, Van den Veyver IB. Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nature Genetics 1999 ; 23 : 185 188. Glaze DG. Commentary : the challenge of Rett syndrome. Neuropediatrics 1995 ; 26 : 78. Schultz RJ, Glaze DG, Motil KJ et al. The pattern of growth failure in Rett syndrome. American Journal of Diseases in Childhood 1993 ; 147 : 633 637. Thommessan M, Kase BF, Heiberg A. Growth and Nutrition in 10 girls with Rett syndrome. Acta Paediatrica 1992 ; 81 : 686 690. Leonard H, Thomson R, Glasson E. et al. A population based approach to the investigation of osteopenia in Rett syndrome. Developmental Medicine and Child Neurology 1999 ; 41 : 323 328. Budden S. Rett syndrome : studies of 13 a ected girls. American Journa l of Medical Genetics 1986 ; 24 : 99 109. Budden S, Meek, M, Henighan C. Communication and oral motor function in Rett syndrome. Developmental Medicine and Child Neurology 1990 ; 32 : 51 55. Morton RE, Bonas R, Minford J, Kerr A, Ellis RE. Feeding ability in Rett syndrome. Developmental Medicine and Child Neurology 1997 ; 39 : 331 335. Witt-Engerstrom I, Forslund M. Mother and daughter with Rett syndrome. Developmental Medicine and Child Neurology 1992 ; 34 : 1022 1023. Budden S. Management of Rett syndrome : a ten year experience. Neuropediatrics 1995 ; 26 : 75 77. Kerr A. Early clinical signs in the Rett disorder. Neuropediatrics 1995 ; 26 : 67 71. Morton RE, Bonas R, Minford J, Tarrant SC, Ellis RE. Respiration patterns during feeding in Rett syndrome. Developmental Medicine and Child Neurology 1997 ; 39 : 607 613. Hunter K. The Rett Syndrom e Handbook. Baltimore, MD : International Rett Syndrome Association, 1999. Naidu S, Hyman S, Piazza K, et al. The Rett syndrome : progress report on studies at the Kennedy Institute. Brain and Development 1990 ; 12 : 5 7. Motil KJ, Schultz R, Brown B, Glaze DG, Percy AK. Altered energy balance may account for growth failure in Rett syndrome. Journa l of Child Neurology 1994 ; 9 : 315 319. Motil KJ, Schultz RJ, Wong WW, Glaze DG. Increased energy expenditure associated with repetitive involuntary movement does not contribute to growth failure in girls with Rett syndrome. Journa l of Pediatrics 1998 ; 132 : 228 233. Reilly S, Skuse D, Mathisen B, Wolke D. The objective rating of oral motor functions during feeding. Dysphagia 1995 ; 10 : 177 191. Skuse D, Stevenson J, Reilly S, Mathisen B. Schedule for oralmotor assessment (SOMA): methods of validation. Dysphagia 1995 ; 10 : 192 202. Reilly S, Skuse DH, Wolke D. The Schedule for Oral Motor Assessment (SOMA). London : Whurr Publishers, 2000. Reilly S, Skuse DH, Poblete X. The prevalence of feeding problems in pre-school children with Cerebral Palsy. Journal of Pediatrics 1996 ; 129 : 877 882. Reilly S, Wisbeach A, Carr L. Managing feeding in children with127 11. S. Reilly and H. Cass neurological problems. In : AM Southall & A. Schwartz (Eds) Feeding Problems in Children : A Guide for Health Professionals. Oxford : Radcli Medical Press, 2000 : 171 190. e 23 Reilly S. Assessment and Management of Females with Rett Syndrome. London : Royal College of Speech and Language Therapists (RCSLT) Bulletin February, 1998. 24 Lloyd D, Pierro A. The therapeutic approach to the child with feeding di culty : III, enteral feeding. In : P Sullivan, L Rosenbloom128(Eds) Feeding the disabled child. Clinics in Developmental Medicine 1996 ; 140 : 132 150. 25 Krick J, Murphy PE, Markham JF, Shapiro BK. A proposed formula for calculating energy needs of children with cerebral palsy. Developmental Medicine and Child Neurology 1992 ; 34 : 481 487. 26 Asaro M. In : K Hunter (Ed.) The Rett Syndrome Handbook. Baltimore : MD : International Rett Syndrome Association, 1999, 231 245.