Longitudinal hand function in Rett syndrome

Loss of hand function is a core feature of Rett syndrome. This article describes longitudinal hand function at 3 time points for 72 subjects participating in the Australian Rett Syndrome Database. Approximately 40% of subjects with some grasping abilities lost skill over the 3- to 4-year period between video assessments. In these subjects, a decrease in hand function was seen less frequently in girls 13 to 19 years old than in those younger than 8 years, in subjects with some mobility compared with those who were wheelchair bound, and in those who had previously been able to finger feed. Relationships with the magnitude of change reflected these findings. Change in hand function did not vary with clinical severity. The results for all subjects were similar to results obtained when analysis was restricted to those with a pathogenic mutation. Variability in the longitudinal course of hand function in Rett syndrome was observed.     

Perspectives on hand function in girls and women with Rett syndrome

Objective: Rett syndrome is a rare neurodevelopmental disorder that is usually associated with a mutation on the X-linked MECP2 gene. Hand function is particularly affected and we discuss theoretical and practical perspectives for optimising hand function in Rett syndrome.

Methods: We reviewed the literature pertaining to hand function and stereotypies in Rett syndrome and developed a toolkit for their assessment and treatment.

Results: There is little published information on management of hand function in Rett syndrome. We suggest assessment and treatment strategies based on available literature, clinical experience and grounded in theories of motor control and motor learning.

Conclusion: Additional studies are needed to determine the best treatments for hand function in Rett syndrome. Meanwhile, clinical needs can be addressed by supplementing the evidence base with an understanding of the complexities of Rett syndrome, clinical experience, environmental enrichment animal studies and theories of motor control and motor learning.     

Rett syndrome as a minicolumnopathy

OBJECTIVE: Rett syndrome is a progressive neurological disorder affecting primarily females. It is characterized by the early regression of acquired language, cognitive functions, social skills, and purposeful hand function. Patients with Rett syndrome are often misdiagnosed as autistic. Recent reports of minicolumnar abnormalities in the brains of autistic and Asperger's syndrome prompted us to search for similar pathology in Rett syndrome. MATERIAL: The patient population consisted of 5 Rett syndrome patients (mean age = 14.4 +/- 4.0 years) and 17 controls (mean age = 14.6 +/- 9.5 years). Tissue was celloidin embedded, sectioned at 35 um and Nissl stained. Images (100x) were taken from Brodmann's areas 9, 21, and 22 from layer III of the left hemisphere. METHOD: Columnar width measurements for these images were obtained with computerized image analysis using previously published algorithms. Each area was analyzed separately with univariate ANOVA, including diagnosis as a fixed factor and age (linear and quadratic terms), and sex as covariates. RESULTS: Diagnosis dependent effects were statistically significant only in area 21 (p = 0.009) even when taking into account a Bonferroni correction for the multiple comparisons. CONCLUSION: Both the regional nature of the changes as well as differences in mean cell spacing differentiates the abnormal minicolumnar morphometry of Rett syndrome from that of autism.     

Observations on hand movements in Rett syndrome: a pilot study

Objectives — It has been assumed that the sterotyped hand movements in Rett syndrome are symmetrical, midline and that they prevent purposeful use of the hands. Their relationship with respiration has not been previously explored. Material and methods — Twenty-five girls whose Rett syndrome included disorganised breathing were selected. Their parents were contacted and interviewed by telephone at their convenience. None refused. Results — The hand movements were asymmetrical in 44% of girls. Those with mainly unilateral hand movements used the same hand for purposeful tasks. The hand movements appeared to change with changing emotional or mental states. In 72% of girls the intensity of hand movements varied directly or inversely with the respiratory pattern. Conclusion — In almost half of the Rett girls the hand stereotypy is asymmetrical and non-midline. It is not the hand movements which prevent purposeful use of the hands. The hand movements together with the erratic breathing are employed as a useful means of communication.     

Motion analysis of stereotyped hand movements in Rett syndrome

Background Rett syndrome is a genetic developmental disorder, and stereotyped hand movements are a striking feature of this condition. The aim of the present study was to subject these movements to objective analysis and compare the results in one girl at different ages. Method The hand movements of a 10‐year‐old girl with Rett syndrome were subjected to accurate, three‐dimensional (3D) computerized motion analysis and compared to two‐dimensional (2D) video analysis of the same girl at 3 years of age. Results Three‐dimensional computerized analysis revealed regular patterns with strong coupling between the hands. Frequency analysis showed a dominant frequency at 1.2 Hz, with a higher component at 2.4 Hz that may relate to the activity of basic rhythm generators. The same coupling characteristics were extracted from standard, 2D video recordings made at the same time as the 3D capture. Conclusion An informal video of the same girl taken when she was 3 years of age was analysed in the same way as the 2D video and showed the same characteristics, indicating the possible future use of automated video analysis for early screening and intervention evaluation.     

Communication and oral-motor function in Rett syndrome

The communication skills, oral-motor function and respiration patterns of 20 girls with Rett syndrome were studied. Loss of communication has been previously recognized as a sign of the onset of Rett syndrome, but oral-motor dysfunction has not been reported. All the girls showed a regression in speech and language function by the onset of stage II Rett syndrome. Changes in oral-motor function and respiration correlated with the progression of the disease from stages II to IV.     

Variation factors of stereotypical hand movements in subjects with Rett syndrome

ABSTRACT

Background: Stereotypical hand movements have been observed in most individuals diagnosed with Rett syndrome. Objectives: To investigate factors that increase or decrease hand stereotypies in individuals with Rett syndrome. Methods: A questionnaire regarding hand stereotypies or purposeful hand behaviours was sent to 1016 schools for special needs education and 204 facilities in Japan. Results: Information was acquired from 216 cases (3–53 years old) with Rett syndrome; 81.9% and 87.6% of individuals had factors that increased and decreased stereotypical hand movements, respectively. Stereotypies were mainly increased by displeasure (63.8%) or pleasure (48.5%), and decreased by somnolence (43.5%), pleasure (30.0%), or food (24.1%). Conclusion: Emotion was the main factor increasing stereotypical hand movements, whereas there were a large number of factors that decreased these movements. The factors that decrease stereotypies could be useful to prevent the skin problems or joint contracture observed in patients with Rett syndrome.     

Anxiety as a marker of severity in acute mania

González‐Pinto A, Galán J, Martín‐Carrasco M, Ballesteros J, Maurino J, Vieta E. Anxiety as a marker of severity in acute mania. Objective: Anxiety has scarcely been studied in acute mania. The aim of this study was to assess anxiety symptoms during manic episodes and their impact on clinical outcomes. Method: Observational, cross‐sectional multicentre study. Anxiety was measured using the Hamilton Anxiety Rating Scale (HARS). Bivariate and multiple linear regression analyses were performed using the HARS score as the dependent variable. Results: Two hundred and forty‐two patients admitted with a diagnosis of acute manic episode according to DSM‐IV TR criteria and a Young Mania Rating Scale >20 were analysed. Mean age was 43 years (SD = 11.9) and 57% were women. Forty‐six per cent of patients (n = 104) presented moderate to severe anxiety symptoms (HARS score >14). Anxiety was significantly associated with severity of manic symptoms (P < 0.0001). Patients with anxiety had 20% longer hospitalizations (mean 21 days, CI95% 19.7–23.7). Conclusion: An association of anxiety symptoms with greater severity in acute mania was demonstrated. The close relationship between anxiety and manic symptoms highlights the need for greater clinical attention to anxiety in this population. Further studies are necessary to determine whether effective treatment of anxiety symptoms could improve clinical and care outcomes.     

The clinical pattern of the Rett syndrome

A case of infantile spasms who developed later on many characteristics of Rett syndrome is described. Rett syndrome was also observed in two sisters. This will probably have great importance for genetic counselling.     

An analogue assessment of hand stereotypies in two cases of Rett syndrome

Stereotype hand movements are one behavioural manifestation of Rett syndrome, a neurodegenerative disorder resulting in severe mental retardation. They are neuropathological in origin, and constitute a barrier to the acquisition and exhibition of more developmentally appropriate behaviours, as well as posing a health risk for some individuals. The present study used an analogue assessment procedure, in which experimental conditions were constructed varying in the consequences delivered contingent upon the exhibition behaviour, to examine environmental correlates to the moment-to-moment expression of these behaviours. Results are discussed regarding their implications for intervention and research into the aetiology of stereotypic behaviours.     

Rett syndrome: clinical and epidemiological aspects in a Brazilian institution

Rett syndrome (RS) is a neurodevelopmental disorder, preferentially found in females and specifically involving the functions on which intelligence and its expression depend--learning, hand use and speech--leaving many others intact. Mutations have been identified at Xq28 on the MECP2 gene (methyl-CpG 2), which selectively silences the expression of other genes whose location is still unknown. This is a study on clinical, diagnostic and epidemiological aspects of RS in a Brazilian sample. It included 33 female patients with chronic encephalopathy without known etiology. RS was diagnosed in 24 patients (72.7%): 17 (70.8%) had classical RS; 5 (20.8%), atypical RS and 2 (8.4%), potential RS. In 9 girls clinical data and/or laboratory studies excluded diagnosis of RS. Among the atypical RS patients, 4 were form fruste and one, congenital form. Among the girls with other encephalopathies, cerebral malformation was the most frequent finding.     

Rett syndrome: clinical and electrophysiologic aspects

Rett syndrome is a neurodevelopmental disorder that almost exclusively affects females. The clinical course as well as the electroencephalogram pattern are characteristic and have been correlated to the clinical stages of the disease. Sixty to 70 percent of the patients develop epilepsy. The aim of this retrospective study was to investigate the correlation between clinical stages and electroencephalogram stages and to more specifically correlate epileptic activity in electroencephalograms with the clinical symptoms of patients. The clinical development and electroencephalogram results of 11 patients diagnosed with Rett syndrome between 1 and 33 years old are compared. In 8 of 11 patients, a correlation was found between electroencephalogram stage and clinical stage. In three of them, epileptic activity in the electroencephalogram was not associated with clinical seizures. Some typical symptoms of Rett patients (hand stereotypies, vacant spells) can be difficult to differentiate from seizures. Therefore application of antiepileptic treatment should be well evaluated, as the clinical course is decisive.     

Genetic and clinical variations in a Norwegian sample diagnosed with Rett syndrome

Background and purposeRett syndrome (RTT) is a neurodevelopmental disorder mainly caused by mutations in MECP2. The diagnostic criteria of RTT are clinical; mutations in MECP2 are neither diagnostic nor necessary, and a mutation in another gene does not exclude RTT. We attempted to correlate genotype and phenotype to see if there are significant clinical associations.MethodsAll available females diagnosed with RTT in Norway were invited to the study. Parents were interviewed, the girl or woman with RTT examined and medical records reviewed. All diagnoses were revisited according to the current diagnostic criteria and exome-based sequencing analyses were performed in individuals without an identified causative mutation. Participants were categorized according to genotypes and RTT diagnosis. Individuals with RTT with and without mutations in MECP2 were compared.ResultsNinety-one individuals were included. A presumed causative mutation was identified in 86 individuals, of these, mutations in MECP2 in 77 individuals and mutations in SMC1A, SYNGAP1, SCN1A, CDKL5, FOXG1 or chromosome 13q in nine. Seventy-two individuals fulfilled the diagnostic criteria for classic and 12 for atypical RTT. Significant differences in early development, loss of hand use and language, intense eye gaze and the presence of early onset epilepsy were revealed in individuals with RTT according to their MECP2 genotypic status.ConclusionUsing the current diagnostic criteria, genetic and clinical variation in RTT is considerable. Significant differences between individuals with RTT with and without MECP2 mutations indicate that MECP2 is a major determinant for the clinical phenotype in individuals with RTT.     

Findings from a multidisciplinary clinical case series of females with Rett syndrome

Systematic data from a multidisciplinary clinical assessment of a large series of females with Rett syndrome (RS; n=87) is presented. Participants' ages ranged from 2 years 1 month to 44 years 10 months. Areas assessed included oromotor skills, feeding problems, growth, breathing abnormalities, mobility, postural abnormalities and joint deformities, epilepsy, hand use and stereotypies, self-care, and cognitive and communication skills. Many previously reported trends in the presentation of RS over time were confirmed, notably the increasingly poor growth and near pervasiveness of fixed joint deformities and scoliosis in adulthood. In contrast, there was a slight trend towards improved autonomic function in adulthood, whereas feeding difficulties increased into middle childhood and then reached a plateau. Improvements in mobility into adolescence were followed by a decline in those skills in adulthood. Levels of dependency were high, confirming findings from previous studies. Despite the presence of repetitive hand movements, a range of hand-use skills was seen in individuals of all ages. Cognitive and communication skills were limited, but there was little evidence of deterioration of these abilities with age. These findings confirm that RS is not a degenerative condition and indicate that intervention and support to maintain and increase motor skills, daily living skills, and cognitive and communicative functioning are appropriate targets for individuals with RS.     

Hand preference,extent of laterality,and functional hand use in Rett syndrome

Residual hand use in functional tasks, extent of laterality, and right or left preference were studied in 145 2- to 24-year-old, postregression Australian subjects with Rett syndrome via parent questionnaire. Hand use was markedly restricted, more for complex than simple and for external (touching food and objects) than internal tasks (scratching, rubbing eyes), suggesting a deficit in cerebral control of external, goal-oriented hand use, which is perhaps genetically determined because there is significantly greater restriction of external tasks in subjects with demonstrated MECP2 mutations. Overall, 33.6% of patients were reported with a left-hand preference, 40.7% with a right-hand preference, and 25.7% with an equal hand preference. Extent of laterality was greater for external than internal and for complex than simple external tasks. Older subjects showed less functional hand use and possibly more overall laterality. However, their hand preference was similar to younger subjects. The anomalous pattern of hand preference in Rett syndrome may be linked to the primary apraxic deficit in this disorder rather than to late manifestation of laterality.