Updated systematic-narrative review on communication intervention in Rett Syndrome: 2010–2022

Figures & data

Figure 1. Flowchart of process used to identify and screen studies for inclusion.

Table 1. Summary of included studies.

Study	Participants	Dependent variable(s)	Intervention characteristics	Main outcomes	Certainty of evidence
1. Ainsworth et al. (2016)	One 14-year-old girl (Anna) with Rett syndrome. Type or stage of Rett syndrome was not specified. The study had eight children (11–16 years) in total, but only had Rett syndrome.	Acquisition of letter-sound correspondence, defined as matching the sound that a letter makes with its orthographic representation.	Intervention was based on the Accessible Literacy Learning (ALL) curriculum (Light & McNaughton, 2009). Anna was taught to look at the printed letters (a, m, p, t, c) and select the letter that matched a sound made by the researcher (e.g., Show me the letter that makes the sound mmmm.). She did this using eye gaze with or without reach approximation. The four-step instructional protocol involved (a) presenting a letter and the sound it made, (b) modeling the correct response, (c) repeating the sound while delaying the model and adding additional foils, and (d) presenting a sound and asking the participant to select the correct letter from a four-choice letter array. Data were collected during tests that occurred prior to each intervention session. Tests involved one presentation of each of the five sounds. Anna received eight teaching sessions on the five letter sounds.	Anna’s mean number of correct responses increased from 1.2 in baseline to 3.0 in the intervention phase.	The certainty of evidence is conclusive because the intervention was evaluated using a multiple-baseline across groups design. Inter-observer agreement and procedural integrity data were adequate.
2. Bartolotta and Remshifski (2013)	Four girls with classic Rett syndrome aged 5, 10, 11, and 14 years. All were at Stage III. None had any spoken language.	Total number of student communication bids directed at an adult and total number of student responses to an adult’s communication bids. Bids and responses could include eye gaze, gestures, vocalizations, body movements, picture symbols, or AAC switch.	During mealtimes, adults were taught to use four strategies to increase student bids and responses. (a) create choice making opportunities, (b) presentAAC devices, (c) wait for child initiation, and (d) respond to child attempts.	Student bids and adult responses increased for all four dyads from Phase 1 (baseline) to Phases 2 and 3 (coaching and post-coaching). Responses decreased at Phase 4 (maintenance).	The certainty of evidence is inconclusive due to the pre-experimental ABCD design and lack of procedural integrity checks. However, adults showed increased bids and responses after baseline, which suggests they were using the targeted strategies.
3. Byiers et al. (2014)	Three females with classic Rett syndrome aged 15, 27, and 47 years. Stage was not specified. MECP2 mutation was confirmed in one participant. All were nonverbal.	Touching a voice-output switch to request preferred stimuli (e.g., TV, attention, or massage). Rate of switch activations per min was calculated for each 5-min session.	A prior assessment indicated that prelinguistic acts (whining, self-injury, or grabbing) were requests for TV, attention, or massage. Intervention aimed to replace these acts with activation of a voice-output switch. Switch use was prompted using most-to-least hierarchy and reinforced with praise and the preferred stimulus. Both independent and prompted responses were reinforced.	When access to preferred stimuli was contingent on prelinguistic acts (i.e., in the baseline or A phases), prelinguistic acts occurred at higher rates than switch activations. When access to preferred stimuli was contingent on switch activations (i.e., in the intervention or B phases), switch activations occurred at higher rates than prelinguistic acts.	The certainty of evidence is conclusive due to the ABAB design and adequate inter-observer agreement and procedural integrity data.
4. Chou et al. (2019)	23 females with Rett syndrome with a mean age of 14 years (range = 3–20). Type and stage of Rett syndrome was not specified, but all had confirmed MECP2 mutation.	The main dependent variables related to communication were participants’ scores on the Receptive, Expressive, and Written Communication sub-domains of the Vineland Adaptive Behavior Scales (Sparrow et al., 1984). Clinical ratings on language and non-verbal communication were also collected.	A group-based music therapy program was implemented with 11 participants. The other 12 served as the control group. Sessions were conducted by a certified therapist with a caregiver (usually the mother) present. Sessions lasted 2 h and occurred twice per week for 24 weeks. Therapy involved vocals and instruments that participants could listen to, look at, and touch. The therapist and caregivers also talked, sang, hummed, and played instruments. Instrument played varied (e.g., stop/start) to encourage participants to follow along.	Participants who received music therapy showed significant increases in their Vineland Receptive sub-domain scores. Clinical ratings of non-verbal communication and language functioning also improved from pretest to post-test for the music therapy group.	The certainty of evidence is inconclusive because participants were not randomly assigned to groups. However, pretest results indicated the two groups had comparable Vineland scores and clinical ratings of communication ability at the start of the study. Inter-rater agreement and procedural integrity do not seem to have been assessed.
5. Fabio et al. (2013)	One, 21-year-old female with Rett syndrome and confirmed MECP2 mutation. She began intervention at 8 years old and was classified as being in Stage IV. She could not speak any meaningful words.	The dependent variable was selecting the correct symbol (e.g., picture, drawing, or printed word, syllable, or letter) from a two-choice array when presented with a corresponding sample stimulus.	Intervention was based on Feuerstein et al. (1988) mediated learning approach, which induces the individual to classify, compare, group, label and convey meaning. Instruction included stating rules reinforcement, interrupting stereotypy, modeling, shaping, fading, and prompting the person to attend. The participant first received pre-training on basic concepts and skills (e.g., staying seated, making choices in a match-to-sample paradigm, and recognizing objects). Pre-training involved 4, 50-min sessions per week from age 8 to 11. She then received discrimination training on matching spoken words to pictures or printed words, matching spoken syllables and letters to printed syllables and letters, selecting printed words to form two-word sentences and responding to questions. This involved 4, 50-min sessions per week from age 11 to 21.	The participant learned 16 words in the matching spoken word-to-printed-word task. She also learned 18 syllables and 19 letters.	The certainty of evidence is inconclusive due to lack of an experimental design. The study involved a B-only (i.e., treatment-only) design. Reliability of data collection and procedural integrity does not seem to have been assessed.
6. Fabio et al. (2018)	Three females with Rett syndrome, aged 29, 30, and 31 years. Type of Rett syndrome was not specified, but all had confirmed MECP2 mutation and all were said to have gone through all four stages. All three were reported to produce sounds. One participant used two words (home and cake) to request.	Dependent variables were (a) producing the correct word or initial letter sound in response to being shown a picture of an object, (b) looking at or touching the correct picture choice, from a two-choice array, when presented with a spoken word instruction (e.g., Touch the duck.). Alpha, beta, and theta bands were recorded using EEG signals.	Intervention involved transcranial direct current stimulation and cognitive empowerment training. Transcranial direct current stimulation occurred 20 min per day over a 10-day training phase. Cognitive empowerment training consisted of prompting and imitation and generalization training.	Intervention was associated with increases in correct words and sounds produced and identified. Alpha beta, and theta bands also increased.	The certainty of evidence is inconclusive due to lack of an experimental design. The design consisted of four sequential phases: Pretest, Training, Post-test, and Follow-up. Inter-rater agreement on utterances was good, but procedural integrity on implementation of cognitive empowerment training does not seem to have been assessed.
7. Fabio et al. (2020)	Thirty-one females with Rett syndrome from 13 to 35 years of age. Mean age was 18 years. All had MECP2 mutation and were in Stages III or IV.	The dependent variables related to communication were production of vowels, phonemes and words in response to picture stimuli.	Participants were randomly allocated to a cognitive empowerment training program with either concurrent sham versus non-sham transcranial direct current stimulation. Participants received 10 daily intervention sessions for 1 week. Sessions lasted 20 min. In the sham condition, 1 mA of stimulation was provided for 30 s, which did not affect neurons. In the non-sham condition, 2 mA of stimulation was provided, Cognitive empowerment training consisted of prompting and imitation and generalization training.	Participants in the non-sham group produced a higher number of vowels and phonemes at post-testing and at the 1-month follow-up. No differences were found for number of words produced.	Certainty of evidence is suggestive due to randomized two-group experimental design. However, checks on reliability of data collection and procedural integrity do not seem to have been undertaken.
8. Fabio et al. (2021)	Twenty-eight females with Rett syndrome from 4 to 22 years of age. Mean age was 12 years. All had MECP2 mutation and were in Stages III or IV.	The dependent variables related to communication were production of correct vowels, phonemes and words in response to picture stimuli.	Cognitive rehabilitation software was configured for use with a Tobii Series-1 eye-tracker. The software presented a target stimulus (e.g., pictures of objects, colors, or shapes) and a distractor. Participants were instructed to give the corresponding word to target stimuli. Correct responses were reinforced with praise. Errors were corrected using verbal prompting and modeling (e.g., What is this? This is bee.). Participants received 30 min of cognitive rehabilitation, 3 days per week for 1 month.	Intervention did not produce a significant effect on the production of correct vowels, phonemes, or words.	Certainty of evidence is suggestive due to the ABAB-ABA withdrawal design. However, checks on reliability of data collection and procedural integrity do not seem to have been undertaken.
9. Hackett et al. (2013)	One, 4-year-old girl with Rett syndrome and confirmed MECP2 mutation. Type and stage of Rett syndrome was not specified. No details were provided on entry-level communication ability	The frequency of turn-taking responses was retrospectively analyzed from videotape. Turn taking included interacting with the therapist via vocalizing, eye gaze, or chest-patting, which were considered to have communicative intent.	14 individual, music therapy sessions were videotaped over a 6-month period. Sessions lasted up to 30 min and were conducted by a registered music therapist. Sessions included a hello and goodbye song and improvization based on the Alvin model (Bruscia, 1987). For example, the participant could direct the therapist’s actions and make choices via eye gaze.	Frequency of turn talking showed a gradual increase over the 14 sessions.	Certainty of evidence is inconclusive due to lack of an experimental design. The study used a B-only (i.e., treatment-only) design. Inter-rater agreement on the scoring of videotapes was good, but procedural integrity data were not collected.
10. Hsieh et al. (2021)	The sample of six children/adolescents (4–19 years) included two girls (Sarah and Anne) with Rett syndrome (aged 4 and 17 years). Type or stage of Rett syndrome was not specified.	Dyadic communication behaviors were coded from 12 video clips obtained during interactions with an adult communication partner. Dyadic communication behaviors included turns and moves (e.g., initiating a conversation and responding to an initiation). Communication functions (e.g., requests for attention and comments) were coded as was stage of communication (e.g., pre-intentional or intentional).	Intervention involved use of eye-gaze assistive technology to control a computer-based communication interface. Naturalistic communication interactions with an adult partner occurred under two conditions: with versus without eye-gaze technology. The eye-gaze technology was the Tobii I-series or PCEye Mini. The communication software was the Communicator 5, Grid 3, or Communicator with WordPower. Communication devices included from 3 to 62 symbols per page. In the non-eye-gaze technology condition, participants used communication boards, eye-gaze frames or iPads.	Significantly more communication initiations were made by the children under the eye-gaze assistive technology condition. Sarah and Anne made more requests for information under the eye-gaze technology condition. They also used the technology more often than gestures in the technology condition.	The certainty of evidence is inconclusive because it is not clear whether or not an experimental design was used. Inter-coder agreement for the video analysis was adequate, but procedural integrity data were not reported.
11. Simacek et al. (2016)	Two females with Rett syndrome, aged 27 and 7 years. The adult had an atypical variant and the child had classic type. Genetic testing had not been completed with the adult. The child had a confirmed MECP2 mutation. Stage of Rett syndrome was not specified. Neither produced any spoken words.	The dependent variable was independent selection of target symbols (photographs of preferred items) from the display of a speech-generating device. The adult’s device had three pages. Each page had a target symbol and three distractors. She selected the target symbol by touching. The child used a Tobii eye tracking device and selected target symbols using an eye gaze response. The Tobii was configured with three pages, each containing a target symbol and one distractor.	Intervention sessions consisted of 5–10 requesting opportunities and lasted 5–15 min. Three to six sessions were conducted per day and 1–2 times per week. Opportunities were initiated by briefly removing a preferred stimulus (e.g., beads or TV) and instructing the participant to Tell me what you want. If the target request did not occur within 1 min, responses were prompted using most-to-least prompting and other stimulus prompting and fading strategies. Correct symbol selections were reinforced by access to the requested item.	Accurate and independent selection of the target symbols increased to 90–100% for the adult and for two of the three items for the child. The child’s request for one item (food) also increased, but performance was more variable, ranging from 14% to 100% over the final 15 intervention sessions.	The certainty of evidence is conclusive due to the multiple baseline across target symbols design and there was adequate inter-observer agreement and procedural integrity data.
12. Simacek et al. (2017)	Three girls (3.5–4 years), but only one (Sidney) had Rett syndrome. Details on mutation, type and stage of Rett syndrome were not provided. Her speech was limited to babbled sounds (ma-ma and ba-ba).	The dependent variable was frequency of requesting responses in three contexts. The response involved activating a BIGmack switch with voice output “more.” The three contexts were requesting food when seated in a high chair, requesting snacks when in the living room, and requesting parent attention when seated on the living room couch.	Parents were taught to use Functional Communication Training (FCT) via telehealth. FCT involved most-to-least prompting of the BIGmack switch and reinforcement of each response by delivering requested item. Parent training involved summarizing the instructional steps and modeling the most-to-least prompt procedure. Up to seven 5-min sessions were conducted per day.	With intervention, use of the BIGmack switch increased and prelinguistic acts (e.g., reach, hit tray) decreased for two of the three targeted requesting contexts (i.e., requests for food and requests for snacks). There was slightly more use of the BIGmack switch than prelinguistic approaching for the requesting attention context.	The certainty of evidence is conclusive due to an adapted multiple probe across requests design and adequate inter-observer agreement and procedural integrity data.
13. Stasolla et al. (2014)	Three girls (8–10 years of age) with Rett syndrome. Details on mutation, type and stage were not provided. All three lacked speech, but made some vocalizations.	Number of items requested by touching photographs or touching pictures on a speech-generating device. The speech-generating device produced relevant voice output (e.g., “orange juice”).	Intervention sessions were 10 min. Sessions occurred 2–4 times per day and 5 days per week over a 4-month period. Participants were taught to make requests for preferred items with a variation of the Picture Exchange Communication System (PECS, Phases 1–3; Bondy & Frost, 2001) and by using a speech-generating device. Participants were prompted to make requests using physical guidance. Requests were reinforced by providing access to the requested item.	The number of requests made per session increased from 0 to 2 in baseline to 5–10 during intervention. The number of requests made per session was comparable under the two conditions (i.e., PECS versus speech-generating device).	The certainty of evidence is suggestive due to the modified alternating treatments with imbedded withdrawal design and adequate inter-observer agreement. However, procedural integrity checks were not reported.
14. Titlestad and Eldevik (2019)	Two (twin) girls (3 years, 7 months old) with Rett syndrome and confirmed MECP mutation. They were at Stage II when intervention began and progressed to Stage III over the course of intervention. Type of Rett syndrome was not specified. Parents reported the girls used vocalizations, eye gaze, and facial expression.	The dependent variables related to communication were participants’ raw scores and age equivalencies for the Receptive, Expressive, and Written Communication sub-domains on the Vineland Adaptive Behavior Scales (Sparrow et al., 2005) and scores from the Assessment of Basic Language and Learning Skills-Revised (ABLLS-R; Partington, 2008).	Starting at 3 years, 7 months of age, the girls received Early Intensive Behavioral Intervention. They received 30–35 h of intervention per week over a period of 33 months. Preschool staff implemented an intervention protocol based on Eldevik et al. (2010) and Smith et al. (1995). These protocols involve a range of strategies (e.g., shaping, prompting, and reinforcement). Teaching goals were derived from the ABLLS-R. Data were collected at intake and after 1, 2 and 3 yrs of intervention.	Vineland Communication scores increased from 31 to 33 points by the end of the intervention. Gains for sub-domains were 14–15 points (Receptive) and 17–18 points (Expressive). Communication). Gains were also evident on the ABLLS-R.	Certainty of evidence is inconclusive due to lack of an experimental design. The study used a B-only (i.e., treatment-only) design, Inter-rater agreement does not seem to have been undertaken, but staff achieved 90% on a treatment fidelity checklist.
15. Vessoyan et al. (2018)	Four girls with Rett syndrome, aged 9, 10, 15, and 15 years. All were at Stage III, but type and mutation confirmation were not reported. Participants used eye gaze, vocalizations, and body movements.	The extent to which participants achieved individualized communication goals (e.g., select messages from AAC device to request item and ask questions) was rated using Goal Attainment Scaling (Kiresuk et al. (1994).	Participants received eye-tracking technology for using speech-generating devices. The devices were configured with from 8 to 30 locations per page. Therapists made five home visits over a 12-month period. During visits, parent and therapist developed communication goals and parents received consultation on use of the eye-tracking technology. They were also consulted on how to promote communication by (a) presuming competence, (b) following the child’s lead, (c) acknowledging responses, and (d) assigning meaning to communication attempts.	All participants were rated as having met or exceeded the expected level of performance for at least one of their two communication goals.	Certainty of evidence is inconclusive due to lack of an experimental design. The study used an A-B-design, but the baseline was derived from retrospective perceptions of participants’ pre-intervention levels of performance. Inter-rater agreement checks were made on goal ratings, but agreement across independent raters was only 50% Procedural integrity does not seem to have been assessed.
16. Wandin et al. (2021)	Three women with Rett syndrome, aged 27, 29, and 31 years. Two had a confirmed MECP2 mutation. Stage and type were not specified. None had any speech.	The dependent variables related to communication were participants’ (a) rate of synthesized words per min, and (b) rate of unique synthesized words per min. Unique words were new words not seen at (a)	Participants were fitted with a gaze-controlled AAC device (Tobii l12+) with communication software (Communicator 5). The AAC devices were configured with communication symbols, such as “MORE”, “FINISHED” and “GOOD.” Participants received 13–16 intervention sessions each lasting 20–30 min over a 6- week period. Intervention involved aided language modeling (Sennott et al., 2016), which involved having the communication partner point to symbols on the AAC device twice per min while speaking.	Moderate to large effects were reported for two participants on both dependent measures. There was no intervention effect for the third participant on synthesized words per min, but a large effect for unique synthesized words.	Certainty of evidence is suggestive due to the ABABA (modified withdrawal) design. Inter-observer agreement was adequate. Formal procedural integrity checks were not conducted, but daily feedback was undertaken with the interventionist to ensure that key aspects of the procedure were implemented correctly.

Note. BIGmack^®, AbleNet, Inc. Roseville, MN.

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