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. 2012 Mar;33(2):461–466. doi: 10.1016/j.ridd.2011.10.007

Contributing to the early detection of Rett syndrome: The potential role of auditory Gestalt perception

Peter B Marschik a, Christa Einspieler a,⁎, Jeff Sigafoos b
PMCID: PMC3261369  PMID: 22119693

Highlights

► First study into the potential role of auditory Gestalt perception for an early detection of RTT. ► The study adds to our understanding of pre-regressional abnormalities in RTT. ► Verbal development in RTT is atypical from the first vocalizations onwards. ► Early atypical verbal behavior is a window to the developing nervous system. ► The study contributes to the early detection of RTT for early intervention.

Keywords: Rett syndrome, Audio experiment, Early identification, Gestalt perception, Vocalization, Babbling, Cooing, Speech, Language

Abstract

To assess whether there are qualitatively deviant characteristics in the early vocalizations of children with Rett syndrome, we had 400 native Austrian–German speakers listen to audio recordings of vocalizations from typically developing girls and girls with Rett syndrome. The audio recordings were rated as (a) inconspicuous, (b) conspicuous or (c) not able to decide between (a) and (b). The results showed that participants were accurate in differentiating the vocalizations of typically developing children compared to children with Rett syndrome. However, the accuracy for rating verbal behaviors was dependent on the type of vocalization with greater accuracy for canonical babbling compared to cooing vocalizations. The results suggest a potential role for the use of rating child vocalizations for early detection of Rett syndrome. This is important because clinical criteria related to speech and language development remain important for early identification of Rett syndrome.

1. Introduction

Rett syndrome, first described by the Austrian neuropaediatrician Andreas Rett (1966), is a profoundly disabling neurodevelopmental disorder that is almost entirely confined to females (Hagberg, Aicardi, Dias, & Ramos, 1983; Neul et al., 2010). It is considered to be an important etiological factor for severe/profound intellectual disability in females with a prevalence of 1:5000 to 1:10,000 live female births (Laurvick et al., 2006). Mutations in the X-linked gene MECP2 were identified as the main cause for Rett syndrome (Amir et al., 1999) affecting a wide range of neurodevelopmental functions such as cognitive processes, purposeful hand use, and communicative abilities (Cass et al., 2003; Kerr, Archer, Evans, & Gibbon, 2006; Matson, Fodstad, & Boisjoli, 2008; Neul et al., 2010; Sigafoos et al., 2011). There are also patients with Rett syndrome originating from mutations in other genes (e.g. FOXG1, CDKL5) and individuals with MECP2 mutations who show no clinical signs. Therefore, the clinical criteria for diagnosis of this disorder are important for early identification and differential diagnosis.

Apart from the classic Rett syndrome, three main variant forms have been described: the preserved speech variant (PSV, Zappella Variant), the early seizure variant (Hanefeld Variant) and the congenital variant (Rolando Variant; Neul et al., 2010). All forms of Rett syndrome, the classic phenotype and its variants, typically show a four-stage course of development: the pre-regression period is followed by an onset of stagnation or regression (at the age of 6–18 months); during the rapid destructive stage (between 1 and 3 years), speech and purposeful hand use are lost and characteristic hand stereotypies become more prominent; the pseudo-stationary stage between pre-school and school age is characterised by cardinal features like breathing irregularities, seizures, autistic-like symptoms, social impairments, unsteady gait, apraxia, and intellectual disability; during the late deterioration stage (at age 15–30 or later), reduced mobility, dystonia and scoliosis are some of the prominent features (Cass et al., 2003; Charman et al., 2002; Dunn & MacLeod, 2001; Hagberg et al., 1983; Kaufmann et al., 2011; Kerr, 2001; Neul et al., 2010; Percy et al., 2010; Percy, 2011; Rajaei et al., 2011).

Although an apparently normal early development had initially been regarded as one of the criteria for classic Rett syndrome, various scientists now considered the disorder to be a developmental disorder that manifests shortly after birth (e.g. Burford, Kerr, & Macleod, 2003; Einspieler, Kerr, & Prechtl, 2005a; Einspieler, Kerr, & Prechtl, 2005b; Marschik, Einspieler, Oberle, Laccone, & Prechtl, 2009; Marschik, Lanator, Freilinger, Prechtl, & Einspieler, 2011a; Temudo, Maciel, & Sequeiros, 2007). A detailed tracking down of parents’ suspicions about early maldevelopment was derived from retrospective home movie analysis (Marschik & Einspieler, 2011). Apart from abnormal early motor development in infants with Rett disorder (Einspieler et al., 2005a, 2005b; Marschik et al., 2009) our studies have also contributed to the delineation of early abnormalities in another key clinical feature of Rett syndrome, a deficit in the developing linguo-cognitive domain (Marschik, Einspieler, Prechtl, Oberle, & Laccone, 2010; Marschik et al., 2011a, 2011b). In particular, we observed an intermittent character of typical and atypical vocalizations from the first months of life onwards. One of the most salient features was an abnormal vocalization type of inspiratory character, i.e. proto-vowel or proto-consonant alternations produced on ingressive airstream and breathy voice characteristics (Marschik et al., 2010, 2011b). Based on these observations and the fact that the typical sound repertoire of the infant develops systematically, we decided to focus on the earliest stages of sound productions to evaluate their potential role for the early detection of RTT.

The most intensively investigated early vocalization type is crying, which has been discussed – if it does not decline with growing age – as a marker for later deviations such as aggressive behavior, eating and sleeping difficulties, hyperactivity or even severe developmental disorders such as autism spectrum disorders or Rett syndrome (Bahi-Buisson et al., 2010; Esposito & Venuti, 2010; Forsyth & Canny, 1991; Papousek & Von Hofacker, 1998; Papousek, Wurmser, & von Hofacker, 2001; Von Kries, Kalies, & Papousek, 2006; Wolke, Rizzo, & Woods, 2002). Apart from crying, characteristics of canonical babbling that should emerge by no later than 10 months of age have been discussed as indicators for developmental disabilities (Nathani, Oller, & Neal, 2007; Oller, 1995; Oller, Eilers, Neal, & Schwartz, 1999): children with Rett syndrome, Down syndrome, Williams syndrome, cerebral palsy or profound hearing impairment were reported to enter the babbling-stage with a significant delay (Levin, 1999; Lynch et al., 1995; Marschik et al., 2011b; Masataka, 2001; Nathani et al., 2007; Tams-Little & Holdgrafer, 1998). Our own studies stressed that it is not only the developmental delay, but also rather a qualitatively deviant appearance of early vocalizations which could be essential for the early detection of Rett syndrome (Marschik et al., 2010, 2011b). Based on these findings we were curious as to whether professional- and/or naive-listeners to audio recordings were capable of distinguishing normal from abnormal early vocalizations.

The aims of the study were to address the following issues and questions: (a) Are listeners able to differentiate between qualitatively normal and abnormal early vocal behavior? (b) Is there a difference in the judgements of age-specific vocalizations during the precanonical stage and canonical stage? (c) Is there a difference in the accuracy of judgements between professional-listeners and naive-listeners; between different age groups of listeners; between female and male listeners; and between parents and non-parents?

2. Methods

2.1. Participants

In total 400 native Austrian–German speakers (267 females and 163 males) were enrolled in an audio experiment on the “assessment of early vocalizations” (RTT-audio experiment from there on). The majority of participants was between 19 and 30 years old; n = 361; 24 participants were between 31 and 40 years and 15 were over 40 years of age. The majority of participants (n = 377) did not yet have any children of their own.

We classified participants into two groups based on their reported professions: First, professional-listeners (n = 61) consisted of speech-language therapists (n = 47), clinical linguists (n = 5), phoniatricians (n = 4), and developmental psychologists (n = 5). However, none of these professionals had expertise in early vocal development of children with genetic disorders. The second group consisted of naive-listeners (n = 339), i.e. medical students (n = 261) and students of general linguistics (n = 78). None of these individuals had training in speech-language development.

2.2. Procedure

From an extensive collection of video footage, audio files were created of either normal vocalizations (cooing and babbling) from typically developing girls (recordings B, D, E) or the vocalizations of girls with Rett syndrome (recordings A, C, F). The sound files of girls with Rett syndrome corresponded to previously reported abnormal inspiratory vocalizations and sequences with intermittent and rapidly changing character of normal and abnormal vocalization patterns (Table 1; Marschik et al., 2010, 2011b). Furthermore, we selected one vocalization sequence of a girl with Rett syndrome, which had been interpreted as normal (recording G). For inclusion the following criteria had to be met: (a) a 100% agreement of normal vs. abnormal vocalizations between two experts (P.B.M. & C.E.); and (b) files meeting criterion (a) were then used for a pilot study with five experts in the field of child development. If all experts agreed on the quality of performance, the files were included in the RTT-audio experiment. Thus a total of seven audio files were included. They comprise four audio files of vocalizations of girls at the cooing stage (recordings A–D; first half a year of life; n = 4; 2 Rett syndrome [RTT] and 2 typically developing children [TD]) and three of the expansion stage or canonical stage (recordings E to G; second half a year of life; n = 3; 2 Rett syndrome, 1 TD; Table 1). Each recording lasted between 23 and 27 s with a Median of 25 s.

Table 1.

Recordings of age-specific vocalizations (age group I = 3–6 months; age group II = 7–12 months) and judgements of the 400 participants.

Age groups I and II Case Sex Vocalization Judgement by the authors (a) Inconspicuous n (%) (b) Conspicuous n (%) (c) No decision n (%)
Recording A I RTT f Inspiratory character Conspicuous 171 (43%) 187 (47%) 42 (10%)
Recording B I TD f Normal Inconspicuous 226 (56%) 139 (35%) 35 (9%)
Recording C I RTT f Inspiratory character Conspicuous 174 (44%) 145 (36%) 81 (20%)
Recording D I TD f Normal Inconspicuous 244 (61%) 90 (23%) 66 (16%)
Recording E II TD f Normal Inconspicuous 339 (85%) 30 (7.5%) 31 (7.5%)
Recording F II RTT f Intermittent character (normal babbling and inspiratory components) Conspicuous 21 (5%) 351 (88%) 28 (7%)
Recording G II RTT f Babbling (pre-selected as inconspicuous sequence by p.b.m, c.e.) Inconspicuous 246 (61.5%) 70 (17.5%) 82 (21%)
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Abbreviations: RTT, Rett syndrome; TD, typically developing, f, female.

The experiment took place in lecture rooms (equipped for up to 20 people) at the Medical University of Graz, the Karl-Franzens-University of Graz, and the University of Applied Sciences Graz, Austria. Two loudspeakers (Bose Companion 2 Series II) on stands were positioned at the front table of the lecture room. All seven target sound files were presented in random order to the two age groups of participants at a level of approximately 60 dB SPL. Each sound file was presented twice with a temporal gap of 10 s, and was rated after the second presentation by the participants. The temporal gap between the different sound files was 30 s.

The participants enrolled in the RTT-audio experiment were asked to fill in a scoring sheet rating the presented audio files as (a) inconspicuous, (b) conspicuous or (c) if they could not decide between (a) or (b). Inconspicuous was defined as age-specific normal vocalizations of typically developing children whereas conspicuous was defined as all deviations from typical verbal behaviors. A correct answer was defined as agreement between participants’ decision and classifications made by the experts (see inclusion criteria mentioned above).

2.3. Data analysis

We used the SPSS package for Windows, version 18.0 (SPSS Inc., Chicago, IL) to determine if there were differences in the ratings made by the two groups of participants and for the vocalizations of typically developing vs. Rett syndrome children. We applied the Pearson Chi square. A p value of less than 0.05 (two-tailed) was considered statistically significant.

3. Results

3.1. Differences between cooing and babbling

The correct identification of inconspicuous vocalizations significantly increased from the cooing stage (56% for recording B and 61% for recording D) to the babbling stage (85% for recording E; p < 0.05). The percentage of incorrect judgements of inconspicuous audio sequences decreased from 35% (recording B) or 23% (recording D) to 7.5% (recording E; p < 0.05) The same held true for the identification of conspicuous audio sequences of girls with Rett syndrome; correct judgements increased from 36% (recording C) or 47% (recording A) to 88% (recording F), whereas 43% (recording A) or 44% (recording C) incorrect judgements decreased to 5% (recording F; p < 0.01; Table 1). The amount of undecided judgements decreased (but not statistically significant) from 10% (recording A) and 20% (recording C) to 7% (recording F; Table 1). Recording G, the seemingly inconspicuous vocalization of a girl with Rett syndrome, was judged inconspicuous by 61.5% of the listeners; 17.5% rated conspicuous, whereas 21% did not decide for either category.

3.2. Professional-listeners and naive-listeners, age and gender differences, parents and non-parents

Professionals had significantly more correct judgements of cooing vocalizations in three out of four recordings: for recording A (75% vs. 54% of linguistics students and 39% of medical students; p < 0.001); recording B (95% vs. 49% of linguistic students and 39% of medical students; p < 0.001); and recording D (67% vs. 59% of linguistics students and 61% of medical students; p < 0.05). For recording C, no difference in the accuracy of judgements was observed. For the babbling stage, however, significantly more students (96% of linguistic students and 84% from medical students) than professionals (75%; p = 0.01) correctly judged recording E as inconspicuous. Recording F did not reveal differences between professional and naive listeners. For recording G professionals (74%) were more often correct than students (62.5% of medical students and 49% of linguistic students; p < 0.01).

Participants above 30 years of age judged recording A more often as conspicuous (73%) compared to participants aged between 19 and 30 years (44%; p < 0.05). Recording B was also judged more often correctly by participants above 30 years of age (95% vs. 53% correct judgements of younger participants; p < 0.001); so was recording D (78% vs. 59% correct judgements; p = 0.05). For recording C and all recordings of the babbling stage, no differences in accurate ratings referring to the participants age could be observed.

Furthermore, there were no gender differences in correct and incorrect ratings for six audio files; the only difference observed was for recording F; slightly more female (89%) than male participants (84%) correctly judged these vocalizations as conspicuous (p < 0.05).

For recordings A–F there were no differences in the rate of correct judgements between parents and non-parents. Participants with own children, however, scored recording G more often as inconspicuous (89%) than those without children (60%; p < 0.05).

4. Discussion

The presented study is the first to experimentally assess the atypicality of early vocal behaviors in Rett syndrome and adds to the understanding of neurobehavioral abnormalities in this neurodevelopmental disorder starting from the first months of life. The experiment focused on the differentiation of early typical vs. atypical vocalizations, the latter being a marker for increasing developmental problems in the speech-language domain of girls with Rett syndrome (Marschik et al., 2010, 2011a, 2011b; Tams-Little & Holdgrafer, 1998). Cooing, i.e. early comfort vocalizations, meet a period when turn-taking between mother and infant begins. In this period spontaneous vocalizations in the alone situation are characterised by alternating cooing and fussing behaviors (Hopkins & van Wulfften Palthe, 1987). The first are regarded as a step into a more elaborate and playful form of vocalization with a function that is related to intuitive parenting and attracting parents. The same holds true for the next stages in verbal development, babbling being the most widely known and most salient realizations that facilitate parental engagement (Locke, 2006) and account for an implicit understanding of how infants sound.

Our aim was to shed light on the potential function of auditory Gestalt perception for the early detection of girls with Rett syndrome. Interestingly, the accuracy for rating verbal behaviors is dependent on the type of vocalization. Canonical babbling seems easier to be classified qualities of, normal or abnormal, compared to cooing vocalizations. If we consider typical development, the percentage of correct judgements was about chance in the cooing period but remarkably increased in the babbling-period. The same effect is demonstrated if we look at the incorrect judgements that significantly decreased in the babbling age. For the atypical development, the picture was even clearer. Correct judgements were more than doubled and incorrect judgments tremendously decreased comparing cooing to babbling vocalizations. The increasing accuracy of our implicit conception of typical and atypical vocal behaviors for more complex vocalizations is in line with previous reports stating that it is easier for listeners to identify syllables compared to precanonical sounds (Nathani & Oller, 2001).

Splitting the groups of listeners into professional- and naive-observers revealed that professionals had significantly more correct judgements compared to naive-listeners during the cooing-period. A possible explanation might lie in the acquired knowledge about the early vocalization period. Interestingly, expertise seemed to somehow adversely affect the judgement of normal babbling behavior. Naive listeners more accurately judged the given recording as compared to professionals. A cautionary interpretation could be that the auditory Gestalt conception might be superimposed by expectations of possible peculiarities. For conspicuous vocalizations, however, naive listeners and professionals scored comparably. Similarly, we could not observe an age-effect of observers for babbling, but accuracy for correct cooing judgements was higher for participants above 30 years of age. This could be explained by the fact that all participants above age 30 had special training related to the field of observation. Interestingly, there were no gender differences except for one recording, which we have no plausible explanation for. In addition, no differences between parents- and non-parents could be observed. The exception where expertise or experience seem to substantially influence the judgements was recording G, the seemingly inconspicuous vocalization of a girl with RTT. Professionals and parents more often scored this recording as inconspicuous affirming the previously documented character of rapidly changing normal and abnormal vocalizations in girls with Rett syndrome (Marschik et al., 2010, 2011b). This behavior is expressed in the percentage of “inconspicuous” judgements on the one hand and in the much higher rate of “no decision” judgements on the other hand. These rates have been shown to be two-thirds less for normal as well as for atypical vocalizations.

Our findings are generally in line with recently published data of Esposito and Venuti (2010), who reported qualitative differences in crying behavior between typically developing toddlers and toddlers with Autism Spectrum Disorder at 18 months of age. Notwithstanding the different age group and another vocalization type observed, our findings are in line with this study, which was also based on retrospective sound files from home-movies, stating that a significant qualitative difference is observable by naive listeners. For girls with Rett syndrome, it has previously been shown that professionals and experienced parents could detect peculiarities in early development (Burford et al., 2003; Burford, 2005; Leonard & Bower, 1998). In a study conducted by Burford et al. (2003), Burford (2005) health professionals without prior knowledge of Rett syndrome were asked to note (any) peculiarities in early development documented by home videos of infants with RTT. Interestingly, and potentially another index for the intermittent character of neurobehavioral manifestations in Rett syndrome, the ratings of normal vs. abnormal behaviors changed for judgements of the same child at different ages (Burford et al., 2003; Burford, 2005). It is important to note, however, that not all peculiarities referring to physical appearance, interaction with surroundings, body movements, postures and vocalizations were seen in all children with Rett syndrome (Burford, 2005; Einspieler et al., 2005a, 2005b; Marschik et al., 2011b).

While this is the first study into the potential role of auditory Gestalt perception for the early detection of Rett syndrome, the results would be interpreted with caution due to several design limitations. One of the limitation of this study is that not all girls wit Rett syndrome meet the milestone of canonical babbling and if babbling appears it is in most cases markedly delayed. Consequently, we only provided one recording of canonical babbling of a girl with Rett syndrome. Another limitation refers to the participants enrolled. On the one hand parents constitute a rather small group of the sample. Being a parent was strongly linked to being a professional. Most of the naive listeners (i.e. students), in contrast, did not have children on their own.

Despite these limitations, the present study could be seen as providing evidence suggesting that the MECP2 mutation influences early brain development in terms of endogeneously generated verbal behaviors from the earliest stages on. Our results also could suggest early abnormality in Rett syndrome before the onset of regression and this could in turn add to the conceptualization of early vocal behaviors as an important parameter to indicate developmental delay (Oller, Eilers, Neal, & Cobo-Lewis, 1998; Oller et al., 1999). One implication of these findings is that early vocalizations of infants should be screened to look for abnormalities which might signify problems in the child's developing nervous system (LaGasse, Neal, & Lester, 2005). Abnormal (conspicuous) vocalizations might point to developmental peculiarities, suggesting a need for follow-up assessment of such infants (LaGasse et al., 2005; Marschik et al., 2011b).

5. Conclusion

It is increasingly acknowledged that the pre-regressional stage of Rett syndrome is less inconspicuous than initially assumed (Burford, 2005; Einspieler et al., 2005a, 2005b; Kerr, 1995; Leonard & Bower, 1998; Marschik et al., 2009, 2011b). A peculiar quality of early vocalizations is together with a marked delay in the onset of expected behaviors. This finding may point to a severe developmental disorder and shall lead to additional observation of developmental trends in these children. The reported findings contribute to the long term aim of early detection for early intervention. To date the evidence supporting current approaches on communication intervention in Rett syndrome is still inconclusive (Sigafoos et al., 2009). Early identification before regression is essential for describing alternative pathways of communicative development and for finding ways of helping affected children make best use of their abilities.

Acknowledgements

We would like to express our sincere gratitude to all parents for providing the audio-data; further to all colleagues who helped to conduct the study, especially Mag. Katrin D Bartl-Pokorny, Professor Ralf Vollmann from the Department of Linguistics at the Karl-Franzens-University of Graz; Professor Berndt Urlesberger from the Department of Pediatrics at the Medical University of Graz; Ing. Gunter Vogrinec for technical assistance; and Miha Tavcar (scriptophil) for copy editing the article. We would like to thank all colleagues and students who volunteered as participants for the experiment. The study was supported by the Austrian Science Fund (FWF; P19581-B02), Koerner Fond, Country of Styria; and the Lanyar Foundation (P325, P337).

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