Rett Syndrome

Rett syndrome is a disorder occurring in girls who, prior to the onset of the disorder (usually between six and eighteen months) have appeared to develop normally (Perry, Sarlo-McGarvey, & Haddad, 1991. Rett syndrome is characterised by a course of development involving sequential progression through a four-stage clinical grouping. As the child progresses through the stages the phenotype changes - with each stage having defined characteristics, and the onset of new behaviours or symptoms and the reduction of others (Sansom, Krishnan, Corbett, & Kerr, 1993). The disabling and handicapping effects of the syndrome are multifaceted with symptoms of the syndrome impacting on cognitive as well as physical development. Rett syndrome has been described as leaving children "profoundly mentally and physically disabled" (Saunders, McCulloch, & Kerr, 1995 p. 496).

The syndrome was first noted by Rett in 1966 but has only received prominence in the literature since the identification of the "characteristic neurodevelopmental phenotype" by Hagberg in 1983 (cited by Sansom et al. 1993; p. 340). In the mid 1980s estimates of prevalence were at 1:15,000 but a 1992 estimate placed the number at 1:10,000 (Sansom et al., 1993). This higher figure may well be attributable to improved identification of the disorder, and increased awareness of the disorder. Rutter (1994) estimated that 40% of individuals with Rett syndrome were incorrectly diagnosed as autistic prior to proper diagnostic methods being formulated for Rett syndrome. There are cases of the syndrome in all parts of the world with approximately 1,420 known cases world wide in 1991 (Van Acker, 1991). Rett syndrome may be responsible for one fourth to one third of progressive developmental disabilities in girls (Van Acker, 1991) and for at least 10% of profound disability in females (Saunders, McCulloch, & Kerr, 1995).

The etiology of Rett syndrome remains unresolved. There is some evidence to indicate a genetic basis, although this remains inconclusive (Van Acker, 1991). In all documented cases where Rett syndrome has been diagnosed in monozygotic twins it has been present in both girls, while only ever in one twin in the case of dizygotic twin girls (Perry, 1991). In some cases there has been a familial pattern with a sister, cousin, aunt and/or niece also with the disorder (Van Acker, 1991), and in one instance a woman with the syndrome gave birth to a daughter who also developed Rett syndrome (Hagberg, Anvret, Percy, & Wahlstrom, 1993). To date the syndrome has been diagnosed in girls only. It has been theorized that this is due to X-linked new mutations resulting in the early abortion of male foetuses and a dominant phenotype in females (Van Acker, 1991). Others have suggested a two step mutation whereby each of the X Chromosomes would be affected: One inherited mutated X chromosome and a somatic mutation at the same point of the other X-Chromosome (Van Acker, 1991) However, Perry (1991) cited two studies which found similar symptoms in two boys. It should be noted that being female is not an inclusion in the necessary criteria - this is the case to avoid creating a bias against finding any male cases (Perry, 1991). Due to the fact that the syndrome has been shown to effect primarily girls this paper refers to the female population.

Attempts to explain the pathophysiology of Rett syndrome have raised several possibilities but no conclusive evidence. Several early studies pointed to abnormal dopamine levels (Van Acker, 1991). Lloyd et al, (1981, cited in Van Acker) found some characteristics of Rett syndrome were also characteristic of boys with Lesch-Nyhan, a syndrome where dopamine levels have been shown to have a causal relationship with the behaviour related (Van Acker, 1991). Recent studies however have failed to replicate this finding (Van Acker, 1991).

Due to the progressive nature of the disorder, and the fact that it is preceded by normal pre and post-natal development, Perry (1991) reported that much research has focused on the likelihood of the syndrome having a metabolic basis. However no consistent evidence for any known such disorder has been found. Hagberg and colleagues (1993) reported that in many cases onset occurs during a respiratory or gastrointestinal viral infection, and suggested that the possibility of the disorder arising through slow viral infection should be considered. Eeg-Olofsson and colleagues (1989, cited in Perry, 1991) suggest from their own and other’s observation of unusually shaped mitochondria in the muscles of individuals with Rett syndrome that "genetically transmitted mitochondrial disease" (p. 283) is the likely underlying mechanism of the syndrome.

In the absence of a biological marker or cause of the disorder a set of inclusionary and exclusionary criteria have been developed for diagnostic purposes.

The age of onset and the duration of each stage is subject to individual differences. Prior to regression comprehension skills and interactional abilities seem appropriate for children’s ages (Woodyatt & Ozanne, 1992). Stage 1 is the period of onset and is characterised by a stagnation in development and a deceleration of head growth. Stage 2 is the period when regression begins and is marked by a loss of expressive language, loss of purposeful hand movement, and a loss of interest in people and the environment. In stage 3 apraxia (difficulty in planning and coordinating movement) and ataxia (poor muscular coordination) become evident and stereotypic hand movements increase, while the girls become more socially interactive and lose most of their autistic tendencies (Woodyatt & Ozanne, 1993). From stage 4 there is no further deterioration of cognitive or interactional skills but physical characteristics, such as ataxia, become worse (Perry, 1991).

If, as the literature suggests, cognitive functioning of girls with Rett syndrome is at an age equivalent of less than eight months, then skills for exploration and contingency play are potentially present in them (Sullivan, Laverick, & Lewis, 1995). Adjustments to programs and environments, as well as provision of equipment and strategies to enable children to engage in purposeful hand movements, could allow the minimization of the handicapping effects of the disorder and so enable the child to develop to the best of her individual potential.

Stereotypic hand movements can be almost continuous while the child is awake and so interfere with the child’s ability to explore objects through manipulation (Van Acker, 1991). These movements most commonly involve wringing, lapping, or tapping of the hands (Perry, 1991). Hand splints have been used as a method of limiting these movements and so allowing the child to attend to people and tasks in her environment (Perry, 1991). Stereotypes in one girl were reduced by 40% when she was engaged in computing activities (Van Acker, 1991), in other studies colourful sound-producing toys requiring input from the child showed similar results, while music therapy has also been shown to encourage purposeful hand use (Van Acker, 1991). Piazza, Anderson & Fisher (1993) successfully trained four girls with Rett syndrome to feed themselves. These findings show promise that programs may be devised to control the stereotypes and so improve the ability of children with Rett syndrome to explore their environment.

A child’s ability to explore and interact with the environment is handicapped by several aspects of the syndrome other than lack of purposeful hand movements.

With the onset of stage two, which occurs between one and three years of age (Perry, 1991), is a rapid decline in social interaction - this has often led to a misdiagnosis of autism (Olsson & Rett, 1987; Rutter, 1994). Lindberg (1991) described that almost overnight girls entering stage two of the disorder "found themselves in some kind of sensory and perceptual chaos. The signals from their own bodies and from the outer world seemed to overwhelm and confuse them instead of giving them useful information" (p. 22). Parents described their daughters as being hypersensitive to all sensory information including food in the mouth, water on the body, sounds, being moved, or touched. These periods were interspersed with brief intervals (minutes to days) of total unresponsiveness.

Anxiety commonly accompanies this decline in social interaction. Sansom et al. (1993) collated parental reports of twenty children under five years and found 85% of girls in the group displayed anxiety, manifested as general distress, hyperventilation, frightened expressions, and self injury. Episodes were precipitated by one or more environmental events such as sudden noises, strangers, new places, changes in routine, some types of music, and being over stimulated by excess activity around them. It was also noted that 80% of the group displayed episodes of crying for no apparent reason. Notable were the authors’ observations that among useful measures found to pacify the children were "slow music, singing, holding, cuddling, massage, water play, and access to favourite toys" (p. 342). The identification of effective means of reassuring and calming individual girls can be seen to be most important in allaying discomfort and encouraging interaction and the confidence to explore the environment within comfortable limits.

In a child’s development the concept of object permanence and the ability to imitate are important to development of knowledge about the world and self. Object permanence, the knowledge that an object continues to exist even when out of range of the senses usually develops during the first nine months (McCune, Kalmanson, Fleck, Glazewski, & Sillari, 1990). Woodyatt and Ozanne (1994) found girls with Rett syndrome in a test situation had very limited understanding of object permanence (failing to look for an interesting item when it left their field of vision) and no imitation abilities. However Fontanesi and Haas (1988, cited in Van Acker, 1991) found that object permanence was relatively preserved in the eighteen girls they studied. Lindberg (1991) also reported that girls actively search for things that are important to them. It appears possible then that object permanence may be preserved, or can at least be facilitated, thereby increasing developmental opportunities for girls with Rett syndrome to learn about objects, other people, and themselves.

Apraxia and ataxia generally appear in combination during stage three of the disorder (Perry, 1991). Lindberg (1991) illustrated the effect apraxia had on a girl with Rett syndrome who appeared motivated to ride a bike. The author described the girl circling the toy, wringing her hands, stamping and breathing heavily, moving a few steps away, then turning back towards the trike. Looking away, looking back, moving closer, concentrating hard - all to no avail as she found herself unable to move towards the toy. Lindberg raised a most pertinent point regarding this issue - perhaps what is seen as aimless or unintentional movement may in fact be quite purposeful, but not seen by an observer as such as it does not achieve a purpose. The author warned against attributing to cognitive deficits that which may in fact be due to apraxia.

Lindberg (1991) proposed that girls with Rett syndrome are able to take in more information than they are able to demonstrate - she gave the example of "the little girl who starts crying when her siblings are talking about her with contempt" (p. 51). This observation has implications regarding the developmental potential of girls with Rett syndrome. Perhaps presentation of stimuli in ways that are not threatening to their anxieties (calmly in a secure uncluttered environment) may enhance the potential of individuals to learn about objects, people and self.

By the age of four years most girls with Rett syndrome have lost all speech skills acquired before the aggression phase (Woodyatt & Ozanne, 1994). From the onset of regression no new words are learned and those previously acquired are gradually lost. By stages 2 and 3 of the disorder skills regress to the normal 8 - 12 month level with no further regression in stage 4 (Woodyatt & Ozanne, 1992). As the initial development of intentional behaviour occurs around the end of the first six months in babies, the literature reports that in most instances girls with Rett syndrome acquired intentional skills which were lost with the progression of the disorder (Budden, Meek, & Henighan, 1990).

Woodyatt and Ozanne, (1992) carried out a study to investigate whether girls with Rett syndrome exhibit intention to communicate - by verbal or nonverbal means. The authors defined intentional communication as "that in which a child shows he is aware of the presence of, and the need for a receiver in a communicative exchange" (p. 157-158). The authors studied a group of six girls and found that all had expressive skills at a pre-intentional level. Subjects’ caregivers did interpret vocal and nonvocal behaviours as having a communicative function, however the authors found there was no expectation or realisation shown by the children that the caregivers would respond. In another study although six girls showed an increase in interactive skills (such as the use of eye contact) as they grew older, all were functioning at a preintentional level. The noted increase was due to the way caregivers interpreted the behaviours rather than a change in acts of communication initiated by the children (Woodyatt & Ozanne, 1993).

Van Acker (1991) noted the importance of detecting communicative behaviours and in responding in a systematic fashion in order to develop formal individual systems of communication. Training can be given to caregivers in the observation of behaviours such as hand-slapping and hyperventilation to determine the intent of these behaviours (Woodyatt & Ozanne, 1992). Eye-pointing is a commonly used form of intentional behaviour used by girls with Rett syndrome, particularly if the individual is severely disabled (Lindberg, 1991). In familiar situations children with Rett syndrome do learn that they can have an effect on their surroundings - such as looking to the biscuit jar to indicate they want a biscuit. Assisting individuals to develop intentional communication methods provides a basis for their continued development of interaction and relationship forming, choice making, problem solving, categorisation, and socially adaptive behaviour skills.

Lindberg (1991) reported that girls with Rett syndrome are able to show context dependent awareness of simple cause and effect situations - for example associate a particular tap with running water. However, in a new room with a different tap transfer would be extremely unlikely. Likewise, a child who has learned to touch an adult’s arm to indicate readiness in a feeding situation is unlikely to transfer this communication means to another situation. A case study by Sullivan, Laverick, and Lewis (1995) showed that a 3.5 year old girl with Rett syndrome could be trained to exercise choice, and that she could generalise what she learned. Through contingency training this girl could exercise choice by using either a switch device operated by her head, or a hand device. Items typically offered for choice were battery operated toys and musical tapes. The author found that the child was able to detect environmental contingencies and modify her behaviour accordingly in response. A follow up of the child at 5 years found her in a classroom where her program included activities which made use of her ability to initiate choice. While these findings are limited they do show promise that intervention and training can increase a child’s developmental opportunities.

It has been noted that girls with Rett syndrome, when compared with other children with other types of profound disability, have relatively good vision (Saunders et al., 1995). The notion of using pictures as symbols of communication has shown promise with girls with Rett syndrome. Lindberg (1991) reported success with this method so long as the picture and the object or event it symbolized were repeatedly shown together to make the relationship clear. Once this relationship became clear to the girls paired presentation of objects, photographs, and drawing could be used to encourage active choice (Woodyatt & Ozanne, 1992).

Until the cognitive abilities of girls with Rett syndrome are better understood it is difficult to determine problem solving potential and ability to categorize. The ability to understand cause and effect has been demonstrated, as discussed, to a very simple level. Of interest is Lindberg’s (1991) observation that when offered two pieces of chocolate cake most girls with Rett syndrome take the larger piece - indicating at least an elementary understanding of size-quantity relationship.

Perry, Sarlo-McGarvey, and Haddad (1991) studied twenty-eight girls with Rett syndrome aged 2 to 19 years with a mean of 9.4 years. Most of this group were able to finger feed themselves and, with assistance, drink from a cup. Most wore nappies with a few on toileting routines and none were able to wash or dress themselves.

As discussed potential for socially adaptive behaviours is limited by several aspects of the syndrome. The period of general withdrawal accompanied by an apparent lack of awareness of surroundings (Woodyatt & Ozanne, 1992) and anxiety produced by change (Sansom et al., 1993) serve to prevent individuals from interacting with others. Opportunities to learn socially adaptive behaviours through imitation and role play are therefore not available (Woodyatt & Ozanne, 1994). The learning of daily living skills such as dressing and feeding is further handicapped by the lack of purposeful hand movement (Piazza, Anderson, & Fisher, 1993) and, as the syndrome progresses, apraxia and ataxia. However, the study by Piazza and colleagues discussed earlier was successful in training four girls with Rett syndrome to feed themselves. This skill not only generates some independence for the girls but also can lead to an increase in social interaction for families at meal times.

While much of the evidence in the literature suggests that the progression of Rett syndrome is such that very little normal development occurs after onset, there is also promise that at least some of the potentially handicapping symptoms can be understood and controlled so that children can be enabled to develop to their own individual potential. Further research is indicated to distinguish further whether deficiencies are the result of cognitive or physical symptoms so that intervention strategies can be designed to maximise development and minimise the handicapping effects of Rett syndrome.

REFERENCES

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Hagberg, B., Anvret, M., Percy, A.K., & Wahlstrom, J. (1993). Aspects on origin - future approach. In B. Hagberg, M. Anvret, & J. Wahlstrom (Eds.), Rett Syndrome- Clinical and Biological Aspects. London: MacKeith.

Lindberg, B. (1991). Understanding Rett Syndrome: A Practical guide for Parents, Teachers, and Therapists. New York: Hogrefe & Huber.

McCune, L., Kalmanson, Fleck, M.B., Glazewski, B., & Sillari, J. (1990). An interdisciplinary model of infant assessment. In S.J. Meisels & J.P. Shonkoff (Eds.), Handbook of early childhood intervention. Cambridge: Cambridge University.

Olsson, B., & Rett, A. (1987). Autism and Rett syndrome: Behavioural investigations and differential diagnosis. Developmental Medicine & Child Neurology, 29, 429-441.

Perry, A. (1991). Rett syndrome: A comprehensive review of the literature. American Journal on Mental Retardation, 96(3), 275-290.

Perry, A., Sarlo-McGarvey, N., & Haddad, C. (1991). Brief report: Cognitive and adaptive functioning in 28 girls with Rett syndrome. Journal of Autism and Developmental Disorders, 21(4), 551-556.

Piazza, C.C., Anderson, C., & Fisher, W. (1993). Teaching self-feeding skills to patients with Rett syndrome. Developmental Medicine and Child Neurology, 35, 991-996.

Rutter, M. (1994). Debate and argument: There are connections between brain and mind and it is important that Rett syndrome be classified somewhere. Journal of Child Psychology and Psychiatry, 35(2), 379-381).

Sansom, D., Krishnan, V.H.R., Corbett, J., & Kerr, A. (1993). Emotional and behavioural aspects of Rett syndrome. Developmental Medicine and Child Neurology, 35, 340-345.

Saunders, K.J., McCulloch, D.L., & Kerr, A.M. (1995). Visual function in Rett syndrome. Developmental Medicine and Child Neurology, 37, 496-504.

Sullivan, M.W., Laverick, D.H., & Lewis, M. (1995). Brief report: Fostering environmental control in a young child with Rett syndrome: A case study. Journal of Autism and Developmental Disorders, 25(2), 215-221.

Van Acker, R. (1991). Rett Syndrome: A review of current knowledge. Journal of Autism and Developmental Disorders, 21(4), 381-406.

Woodyatt, G., & Ozanne, A. (1994). Intentionality and communication in four children with Rett syndrome. Australia and New Zealand Journal of Developmental Disabilities, 19(3), 173-183.

Woodyatt, G.C., & Ozanne, A.E. (1993). A longitudinal study of cognitive skills and communication behaviours in children with Rett syndrome. Journal of Intellectual Disability Research, 37, 419-435.