Three different profiles: Early socio-communicative capacities in typical Rett syndrome,the preserved speech variant and normal development

Background and aims: This is the first study aiming to compare pre-diagnostic socio-communicative development of a female with typical Rett syndrome (RTT), a female with the preserved speech variant of RTT (PSV) and a control toddler.

Methods: We analysed 1275?min of family videos at the participants’ age between 9 and 24 months and used the Inventory of Potential Communicative Acts (IPCA) to delineate their repertoires of communicative forms and functions.

Results: The results revealed different profiles for the three different conditions. The repertoire of communicative gestures and (pre)linguistic vocalizations was most comprehensive in the control toddler, followed by the female with PSV and the female with RTT.

Conclusion: These findings contribute to the growing knowledge about early developmental abnormalities in RTT. In order to define distinctive profiles for typical and atypical RTT and evaluate their specificity, a larger body of evidence is needed.     

Development of socio-communicative skills in 9- to 12-month-old individuals with fragile X syndrome

We investigated the early socio-communicative development of individuals with fragile X syndrome (FXS) by undertaking a retrospective analysis of family videos. Videos were analyzed to identify existing communicative forms and functions. Analyses were undertaken on seven children who were later diagnosed with FXS. The children were filmed when they were 9–12 months old and before being diagnosed. Fourteen different communicative forms and six different communicative functions were observed. All participants were observed to express the functions of ‘Attention to self’ and ‘Answering’, but none indicated ‘Requesting action’, ‘Requesting information’, ‘Choice making’, or ‘Imitating’. Results suggest that children with FXS may have a limited range of communicative forms and functions when they are from 9 to 12 months of age. However, further research is necessary to gain a specific developmental profile of socio-communicative forms and functions in FXS.     

Profiling early socio-communicative development in five young girls with the preserved speech variant of Rett syndrome

Rett syndrome (RTT) is a developmental disorder characterized by regression of purposeful hand skills and spoken language, although some affected children retain some ability to speech. We assessed the communicative abilities of five young girls, who were later diagnosed with the preserved speech variant of RTT, during the pre-regression period (aged 12-24 months). Videotapes, obtained by parents during routine family situations and celebrations, were analyzed to identify communicative forms and functions used by these toddlers. Non-verbal communicative forms dominated over verbal-communicative forms for six of the eight identified communication functions. Although the girls used various non-verbal forms to make requests, for example, none of the individuals were observed to make choices or request information. Early peculiarities in the speech-language domain during the first year of life became more prominent and evident during the second year of life as general differences between typical development and atypical development become more obvious in RTT. These findings highlight the importance of assessing socio-communicative forms and functions at early age in children with RTT. The results suggest that speech-language functions did not appear to play a major role in the children's communicative attempts. We conclude that, even among children with the preserved speech variant, socio-communicative deficits are present before regression and persist after this period.     

Peculiarities in the gestural repertoire: An early marker for Rett syndrome?

We studied the gestures used by children with classic Rett syndrome (RTT) to provide evidence as to how this essential aspect of communicative functions develops. Seven participants with RTT were longitudinally observed between 9 and 18 months of life. The gestures used by these participants were transcribed and coded from a retrospective analysis of a video footage. Gestures were classified as deictic gestures, play schemes, and representational gestures. Results of the analysis showed that the majority of gestures observed were of deictic character. There were no gestures that could be classified as play schemes and only two (e.g., head nodding and waving bye bye) that were coded as representational or symbolic gestures. The overall repertoire of gestures, even though not necessarily delayed in it's onset, was characterized by little variability and a restricted pragmatic functionality. We conclude that the gestural abilities in girls with RTT appear to remain limited and do not constitute a compensatory mechanism for the verbal language modality.     

Early speech-language development in females with Rett syndrome: focusing on the preserved speech variant

Aim Our aim was to contribute new findings related to the pre‐regressional verbal development of females with a variant of Rett syndrome (RTT) as the loss of spoken language is one of the key clinical features of RTT, and it would be of particular interest to study the early speech–language development of females who are considered to have preserved some speech–language abilities. Method We analysed 461 minutes of audio–video recordings containing play situations and the daily routines of six females (aged 7 to 24 months; mean birthweight 3057g, SD 195g) with the preserved speech variant (PSV) of RTT. All videos were recorded by parents and analysed retrospectively after the diagnosis PSV was made. Results From the age of 7 months onwards, we observed two types of vocalizations, appearing intermittently: (1) apparently normal sequences; and (2) atypical (i.e. inhalatory, pressed, or high‐pitched crying‐like) vocalizations. Some participants failed to reach the milestone of canonical babbling. We observed a limited phonological and lexical complexity and a restricted compositional variability. Volubility was reduced during the whole period under observation. Hand stereotypies with simultaneous atypical vocalizations appeared only during the second year of life. Interpretation The intermittent character of normal versus abnormal verbal behaviours might contribute to an early identification of children with a possible genetic mutation, and provides evidence that speech–language functions are abnormal from the very beginning.     

How facial expressions in a Rett syndrome population are recognised and interpreted by those around them as conveying emotions

Rett syndrome (RTT) is a neurodevelopmental disorder, including autonomic nervous system dysfunctions and severe communication impairment with an extremely limited ability to use verbal language. These individuals are therefore dependent on the capacity of caregivers to observe and interpret communicative signals, including emotional expressions. People in general, including therapists tend to focus on changes in facial expressions to interpret a person's emotional state or choices, but with this population it is difficult to know if the interpretations are correct. The aims of this study were to investigate if the Facial Action Coding System (FACS) could be used to identify facial expressions, and differentiate between those that expressed emotions and those that were elicited by abnormal brainstem activation in RTT. The sample comprised 29 participants with RTT and 11 children with a normal developmental pattern, exposed to six different musical stimuli during non-invasive registration of autonomic brainstem functions. The results indicate that FACS makes it possible both to identify facial expressions and to differentiate between those that stem from emotions and those caused by abnormal brainstem activation. This knowledge may be a great help to an uninitiated observer, who otherwise might incorrectly interpret the latter as an expression of emotion.     

Developmental profile of speech-language and communicative functions in an individual with the Preserved Speech Variant of Rett syndrome

Objective: We assessed various aspects of speech-language and communicative functions of an individual with the preserved speech variant of Rett syndrome (RTT) to describe her developmental profile over a period of 11 years.

Methods: For this study, we incorporated the following data resources and methods to assess speech-language and communicative functions during pre-, peri- and post-regressional development: retrospective video analyses, medical history data, parental checklists and diaries, standardized tests on vocabulary and grammar, spontaneous speech samples and picture stories to elicit narrative competences.

Results: Despite achieving speech-language milestones, atypical behaviours were present at all times. We observed a unique developmental speech-language trajectory (including the RTT typical regression) affecting all linguistic and socio-communicative sub-domains in the receptive as well as the expressive modality.

Conclusion: Future research should take into consideration a potentially considerable discordance between formal and functional language use by interpreting communicative acts on a more cautionary note.     

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

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

What studies of family home movies can teach us about autistic infants: A literature review

The current study reviewed all prior studies conducted on family home movies of infants who would be later diagnosed with autism spectrum disorder (ASD). Out of 41 original reports found since 1975, we retained 18 studies (317 films, maximum), sorted according to their methodological design using a quality grid. In the first 2 years of life, signs that differentiated children with ASD from children with developmental delays were as follows: less of a response to their name, less looking at others, lower eye contact quality and quantity, less positive facial expression and intersubjective behaviors (e.g., showing shared attention). Studies focusing on regression confirmed the clinical validity of the phenomena. We conclude that findings from home movies studies along with prospective studies have created the bases for identification of infants and toddlers at risk of developing ASD before the 18–24-month period, despite early diagnosis of autism remains a complex challenge.     

Comparing social reciprocity in preserved speech variant and typical Rett syndrome during the early years of life

This study compared early markers of social reciprocity in children with typical Rett syndrome (RTT) and in those with the preserved speech variant (PSV) of RTT. Retrospective video analysis of 10 toddlers with typical RTT and five with PSV investigated participants’ orientation to their name being called between the ages of 5 and 24 months, prior to their diagnosis. From analysis of the recordings two distinct profiles were apparent. Although response rate was higher in girls with typical RTT than PSV at 5 to 8 months this noticeably reversed from 9 to 12 months onwards. By two years of age there was a markedly higher rate and range of responses from girls with PSV. This study contributes to the delineation of different profiles for the variants of RTT.     

Lexical and grammatical development in a child with cochlear implant and attention deficit: A case study

This is the first study to explore lexical and grammatical development in a deaf child diagnosed with Attention Deficit Hyperactivity Disorder, Inattentive sub-type (ADHD/I). The child, whose family language was Spanish, was fitted with a cochlear implant (CI) when she was 18 months old. ADHD/I, for which she was prescribed medication, was diagnosed 3;6 years later. Speech samples were videotaped over the first 4 years of CI use and during a follow-up session 1 year later. Samples were transcribed according to CHAT conventions and several measures of expressive language were obtained. Receptive language was evaluated with standardized tests. Results show that while some aspects of her development seemed relatively positive (e.g., acquisition of verbal morphemes at the same auditory age as typical children), other characteristics were atypical for a CI user: (1) preference for paralexical expressions in early lexicon; (2) lexical errors in colours and other abstract words; and (3) low MLU and varied grammatical errors including disorganized discourse. Medication had a positive effect on all these characteristics, providing evidence of a link with ADHD/I. This study concludes that ADHD/I had a direct impact on the lexical and grammatical development in this child, as well as an indirect influence over her communicative style. More studies are needed to explore language characteristics of children with CI and ADHD.     

Communication assessment for individuals with Rett syndrome: A systematic review

We reviewed studies that aimed to determine whether behaviors, such as body movements, vocalizations, eye gaze, and facial expressions, served a communicative function for individuals with Rett syndrome. A systematic search identified eight studies, which were summarized in terms of (a) participants, (b) assessment targets, (c) assessment protocols, (d) main findings, and (e) evidence of communication. The eight studies included 41 females with Rett syndrome, ranging from 2.7 (years.months) to 36 years of age. All studies used direct behavioral observations to assess participants’ behavior. Half the studies also used standardized assessments and interviews. Evidence of communication behavior was found for at least some participants in each study, but the validity of this evidence is unknown. Still, the observation-based approaches described in these studies may enable clinicians to identify a range of potential communicative forms and functions, which could be useful for intervention planning.     

Neurophysiology of Rett syndrome

Neurophysiological studies on Rett syndrome (RTT) are reviewed, and pathophysiology of RTT is discussed. The electroencephalography (EEG), sensory evoked potentials (SEP), sleep–wake rhythm study and polysomnography (PSG) study showed age-dependent characteristics. PSG revealed the brainstem and midbrain monoaminergic systems are deranged from early developmental stage, that is serotonin and noradrenaline systems seem to be hypoactive and dopaminergic system is also hypoactive associated with receptor supersensitivity. These monoaminergic systems are known to influence the maturation of the higher neuronal systems at specific areas and at specific ages. Particularly the synaptogenesis of the cerebral cortex is modulated by region or layer specifically from an early stage of the development. The observations made in EEG and SEP studies also suggested specific subcortical and cortical involvements taking place during the development. The age-dependent appearance of characteristic clinical features of RTT, and the variation of the clinical severities, e.g. classical, variant, form fruste, etc., can also be explained by the specific features of these monoaminergic systems. Furthermore, analysis of the components of rapid eye movement sleep suggested the onset of RTT lies between 36 gestational weeks to 3–4 months postnatally. The discovery of the mutations of methyl-CpG-binding protein 2 (MECP2) gene as the causative gene of RTT is an epoch helping not only to understand the pathophysiology of RTT but also various neurodevelopmental disorders.     

How Young Children Treat Objects and People: An Empirical Study of the First Year of Life in Autism

Objective. To figure out features of autism before the age of one and to explore the pathways of early social and nonsocial attention in autism through home movies.Method. Home movies of 15 children later diagnosed with autism, are compared with home movies of 13 typical children. The films of the two groups have been mixed and rated by blind observers through a Grid composed of social and nonsocial item and applied to two age ranges: 0–6 months (T1) and 7–12 months (T2). Two MANOVAs, an ANOVA and discriminant analyses were applied.Results. Significant differences between the two groups were found only for the item in the Social area at T1 but not at T2, when groups did not differ in either social or nonsocial areas. At T2 children with autism had significantly higher scores in the nonsocial area while normal children did not show significant differences between areas. Discriminant analyses revealed that social attention can distinguish the two groups at T1 but not at T2.Conclusions. The fundamental impairment of joint attention in autism could be considered a consequence of the early atypical developmental gap and of a later disconnection between attention to people and objects. Abnormal developmental trajectories for social and nonsocial attention could help us in the future to understand relationships between adaptive capacities and symptoms, and set the stage for appropriate early screening instruments.This study was supported by grant RC 6/02 from National Institute of Health.     

Neurophysiological responses to music and vibroacoustic stimuli in Rett syndrome

People with Rett syndrome (RTT) have severe communicative difficulties. They have as well an immature brainstem that implies dysfunction of the autonomic nervous system. Music plays an important role in their life, is often used as a motivating tool in a variety of situations and activities, and caregivers are often clear about people with RTTs favourites. The aim of this study was to investigate physiological and emotional responses related to six different musical stimuli in people with RTT. The study included 29 participants with RTT who were referred to the Swedish Rett Center for medical brainstem assessment during the period 2006–2007. 11 children with a typical developmental pattern were used as comparison. A repeated measures design was used, and physiological data were collected from a neurophysiological brainstem assessment. The continuous dependent variables measured were Cardiac Vagal Tone (CVT), Cardiac Sensitivity to Baroreflex (CSB), Mean Arterial Blood Pressure (MAP) and the Coefficient of Variation of Mean Arterial Blood Pressure (MAP-CV). These parameters were used to categorise brainstem responses as parasympathetic (calming) response, sympathetic (activating) response, arousal (alerting) response and unclear response. The results showed that all participants responded to the musical stimuli, but not always in the expected way. It was noticeable that both people with and without RTT responded with an arousal to all musical stimuli to begin with. Even though the initial expressions sometimes changed after some time due to poor control functions of their brainstem, the present results are consistent with the possibility that the RTT participants’ normal responses to music are intact. These findings may explain why music is so important for individuals with RTT throughout life.     

A controlled study of formal thought disorder in children with autism and multiple complex developmental disorders

Along with well-defined categories in classification systems (e.g., autistic disorders and attention-deficit/hyperactivity disorder (ADHD)), practitioners are confronted with many children showing mixed forms of developmental psychopathology. These clusters of symptoms are on the borderlines of more defined categories. The late Donald Cohen proposed heuristic criteria to study a group defined by impaired social sensitivity, impaired regulation of affect, and thinking disorders under the name multiple complex developmental disorders (MCDD). Although these children meet criteria for pervasive developmental disorder--not otherwise specified (PDD-NOS), they have additional important clinical features, such as thought disorder. After highlighting similarities and differences between MCDD and comparable groups (e.g., multidimensionally impaired children), this paper presents the findings of a study comparing formal thought disorder scores in children with MCDD to children with autism spectrum diagnoses, such as autistic disorder (AD), and to children with nonspectrum diagnoses, such as ADHD and anxiety disorders. METHODS: Videotaped speech samples of four groups of high-functioning, latency-aged children with MCDD, AD, ADHD, and anxiety disorders were compared to a control group of normal children using the Kiddie Formal Thought Disorder Rating Scale (K-FTDS). RESULTS: High formal thought disorder scores were found both in the AD and MCDD groups, low rates in the ADHD groups, and no thought disorder in the anxiety disorder and normal control groups. The severity of formal thought disorder was related to verbal IQ scores within the AD and MCDD groups. CONCLUSION: High formal thought scores in children with complex developmental disorders, such as AD and MCDD, appear to reflect impaired communication skills rather than early signs of psychosis.     

Assessing the Early Characteristics of Autistic Disorder using Video Analysis

The behaviours of infants were observed using home videos, in an attempt to identify social difficulties characteristic of infants with autistic disorder. Three groups of infants were analysed: 15 infants who had later been diagnosed with autism, 15 infants who had a developmental or language delay, and 15 typically developing infants. Social behaviours were coded using both quantitative and qualitative measures. The principal discriminating items between the groups were found to be 'peer interest', 'gaze aversion', 'anticipatory postures', and 'proto-declarative showing'. The results suggest that these children later diagnosed with autism are clinically distinct from their peers before the age of two years, and that there are clearly observable behaviours which are important predictors of autistic disorder in pre-verbal children.     

Highlighting the first 5 months of life: General movements in infants later diagnosed with autism spectrum disorder or Rett syndrome

We review literature identifying an association between motor abnormality in the first 5 months of infancy and later diagnosis of autism spectrum disorder (ASD) or Rett syndrome (RTT). The assessment of the quality of early spontaneous movements (also known as the assessment of general movements; GMs) is a diagnostic tool that has repeatedly proven to be valuable in detecting early markers for neurodevelopmental disorders. Even though the rate of occurrence of abnormal GMs is exceedingly high in infants later diagnosed with ASD, we endorse further studies using this method either based on family videos or its prospective implementation in high-risk sibling studies to evaluate the power of GM assessment as one potential marker for early maldevelopment in this cohort.     

Age of Diagnosis in Rett Syndrome: Patterns of Recognition Among Diagnosticians and Risk Factors for Late Diagnosis

PurposeDiagnosis of Rett syndrome (RTT) is often delayed. We sought to determine the type of physician who typically makes the RTT diagnosis and to identify risk factors for delayed diagnosis.MethodsA total of 1085 participants from the multicenter longitudinal RTT natural history study with classic and atypical RTT were recruited between 2006 and 2014. Age of diagnosis, diagnostician, diagnostic criteria, and clinical and developmental data were collected.ResultsAmong 919 classic and 166 atypical RTT participants, the median diagnosis age was 2.7 years (interquartile range 2.0-4.1) in classic and 3.8 years (interquartile range 2.3-6.9) in atypical RTT. Pediatricians made the diagnosis of classic RTT rarely (5.2%); however, the proportion diagnosed by pediatricians has increased since 2006. Since the first diagnostic criteria, the age of diagnosis decreased among subspecialists but not pediatricians. Odds of a pediatrician making the diagnosis of classic RTT were higher if a child stopped responding to parental interaction, and lower if they possessed gastroesophageal reflux, specific stereotypies, lost babbling, or the ability to follow commands. Delayed acquisition of basic gross motor skills or finger feeding was associated with younger diagnosis; delayed acquisition of higher level fine motor skills, later onset of supportive features, and normal head circumference were associated with late diagnosis. Thirty-three percent with microcephaly before 2.5 years were diagnosed after the median age of 2.7 years.ConclusionsAge of RTT diagnosis has improved among subspecialists, and pediatricians have made the diagnosis of classic RTT more frequently since 2006. Strategies for educating diagnosticians should incorporate specific risk factors for delayed diagnosis.     

Pragmatic impairments in adults with childhood diagnoses of autism or developmental receptive language disorder

Audiotaped conversational samples from adults diagnosed as having autistic disorders (n=15) or developmental receptive language disorders (n=17) in childhood were transcribed and analyzed using methods based on those of Bishop and Adams (1989). Subjects with autism showed substantially greater pragmatic impairment not explicable by generalized impairment of verbal skills. This was mainly due to autistic subjects' greater difficulty in forming context-relevant communicative intentions; in contrast, pragmatic impairments arising from failures in translating intentions into spoken utterances (i.e., impairments at the level of execution) did not distinguish between the groups. In both diagnostic groups, impairment in forming appropriate communicative intentions was closely related to more generalized impairment of reciprocal social behavior.The author was supported by the Bethlem Royal and Maudsley Hospital Research Fund. Lynn Mawhood very kindly provided all of the primary data and extracted the conversational samples from her recorded interviews. I also thank Dorothy Bishop, Mary Crowson, Helen Eales, and Professor Sir Michael Rutter for advice and help in various aspects of the study.