Rett syndrome (RTT) is a severe, neurodevelopmental disorder mainly caused by mutations in the MECP2 gene, affecting around 1 in 10,000 female births . Clinical manifestations include severe linguistic and motor impairments that are the core of phenotype symptoms. A child affected by RTT initially appears to follow a typical development path, but at about 18 months of age a subtle regression in developmental acquisitions begins, opening the path to the clinical stages . Loss of previously acquired language skills and of purposeful hand use, increasing difficulties in motor abilities (dyspraxia) and mental retardation are the clearest signs of regression involved in RTT. Other typical signs of RTT appear including hand stereotypies—such as handwashing, hand-wringing, hand-mouthing—breathing disorders (breath holding and hyperventilation), ataxia, agnosia, bruxism [3, 4, 5, 6].
Several assessments on patients with RTT have been conducted on cognitive abilities, on communicational abilities and on motor abilities [7, 8, 9, 10, 11]; only few of these have carried out a global functional assessment of all the abilities of these patients. Assessment of the cognitive skills of patients with RTT, as well as other individuals with severe motor and communication limitations, is extremely challenging.  Neuropsychological and cognitive assessments are generally developed for and standardized with typically developing children who do not have physical impairments.  When standard assessment procedures requiring manual motor functioning for responding have been used to evaluate cognitive functioning, patients with RTT generally achieve age-equivalent performances close to young infants [13, 14]. Severe physical, language, and social impairments impose a wide range of limitations [2, 3, 4, 5]. With reference to communication abilities, some studies [15,16] have aimed to recognize any communicative acts (vocalizations, hand movement stereotypies, body movements, facial expressions, or eye gaze) that would represent a consistent and unequivocal response used by participants with RTT. With respect to communication abilities, Woodyatt and Ozanne  reported that literature indicates that the majority of RTT patients are at a pre-intentional level of development with only a few patients able to signal intentions. Recent investigations  in which RTT patients received intensive cognitive rehabilitation using the assessment of non-verbal communication and language precursors have shown that they can go beyond the stage of pre-intentional level of development and that it is possible to teach them the understanding of subjectivity, starting from simple non-epistemic mental states (emotions, desire-emotion), passing then to more complex ones, such as beliefs and false beliefs. Currently, several studies have attempted to assess RTT cognitive processes through new technologies [19,20,21,22,23,24]. Fabio et al.  have investigated whether eye-tracking technology can be useful in RTT. This study demonstrated the efficacy of eye-tracking technology as a valid instrument in the assessment and rehabilitation of RTT.
With reference to the assessment of motor abilities, available clinical scales do not comprehensively capture the variability of presentation of gait and postural abnormalities in Rett Syndrome patients. Griffiths scales  appear too specific to assess peculiar patterns of (loco-)motor derangements in RTT. In addition, the standardization sample included children aged 0–72 months and therefore, similar to the standardization sample of the Bayley scales , is not appropriate to test older children or adolescents. There is another motor scale specific for RTT and already validated: the Rett Syndrome Gross Motor Scale (RSGMS) . Rodocanachi et al. , in a new standardized scale, the Rett Syndrome Motor Evaluation Scale (RESMES), added postural transitions and walking up or downstairs. RESMES items are centered on the International Classification of Functioning construct of patients’ capacity, which reflects what an individual can do in a semi-standardized environment and have been conceived to capture fine-grained characteristics of movement. Regarding a general assessment, there are two scales that can be used to assess children with special needs: the Portage Guide to Early Education Checklist  and the Bayley Scales of Infant Development . The Portage Guide to Early Education Checklist  was developed by the Portage Project home intervention program which has been serving preschool multiple children with special needs in Wisconsin, USA. The guide has two parts: a developmental checklist which lists sequential behaviors from birth through five years of age in five learning areas and a set of curriculum cards which match each of the 450 behaviors listed on the checklist. The check-list has been used to pinpoint behaviors and measure change. The cards have been used in establishing individual home training prescriptions . The Bayley Scales of Infant Development  consist of a mental scale of 103 items and a motor scale of 81 items. The scales have been designed to measure growth and development from birth to 30 months of age. The instrument was developed primarily for clinical and research use. According to Holden , the Bayley Scales have been invaluable in filling a longstanding need for a well standardized, reliable instrument to assess the developmental progress of infants.
With reference to the global assessment of the abilities in Rett syndrome, there are few instruments that can measures the global functional abilities of RTT patients. Some assessments have been carried out by interviewing the parents or caregivers using the Vineland Adaptive Behavior Scales-Interview second edition (VABS), and the Rett Assessment Rating Scales (RARS). VABS  is subdivided into four domains: communication; daily living; socialization; and motor skills. The interviewer asks general questions pertaining to the patient’s functioning in each domain and uses the responses to rate the examinee on each critical behavior item (2: always present, 1: sometimes present, 0: seldom or never present). Typical interviews require approximately one hour. A total score is computed by summing the individual ratings for each scale. Another general assessment scale has been created to evaluate level of severity in RTT patients - RARS . This scale is organized into seven domains: cognitive, sensorial, motor, emotional, autonomy, typical characteristics of the disease and of behavior. A total of 31 items was generated as representative of the profile of RTT. Each item is provided with a brief glossary explaining its meaning in a few words. Each item is rated on a 4-point scale, where 1 = within normal limits, 2 = infrequent or low abnormality, 3 = frequent or medium-high abnormality, and 4 = strong abnormality. Intermediate ratings are possible; for example, an answer between 2 and 3 points is rated as 2.5. For each item, the evaluator circles the number corresponding to the best description of the patient. After a patient has been rated on all 31 items, a total score is computed by summing the individual ratings. This total score allows the evaluator to identify the level of severity of RTT, conceptualized as a continuum ranging from mild symptoms to severe deficits (Mild = 0–55; Moderate = 56–81; Severe = > 81).
Summarizing, the main limitations of the scales presented here are firstly, in some scales like VABS and RARS parents and caregivers are requested to evaluate patients’ abilities through simple observation and not through direct evaluation by therapists; secondly, in some of these scales not all the areas of manifestations in RTT are considered (behavioral, intellectual, academic, neuropsychological and psychosocial); finally not all of these scales are presented hierarchically and they may not be valid for the assessment or for suggesting all the next level of the steps necessary for any eventual intervention.
In the present work, we proposed GAIRS to overcome all these limitations. The aim of this study is to examine the preliminary psychometric characteristics of the GAIRS Checklist. Furthermore, the aim is to examine the validity of GAIRS with test-retest correlation, convergent validity with similar functional measurements such as the Vineland scales, divergent validity with severity of disease scale such as the RARS scale and neuropsychiatric evaluations. A specific GAIRS Checklist has been developed to assess behavioral, intellectual, academic, neuropsychological and psychosocial manifestations in patients with Rett Syndrome. The purpose of the Checklist is to offer an easy-to-use, short and accessible tool for every health-care professional to assess all the abilities but also to identify patients needing next-step evaluation and treatment. Thanks to the hierarchical order of all the targets assessed in each area of GAIRS, this Checklist can be a useful instrument not only for assessment but also for any eventual intervention.