Stereotypic Hand Research Articles

Rett syndrome

Rett syndrome is a rare, progressive, neurodevelopmental disorder that has been reported only in the girl child. We describe the case of a 6.9-year-old girl with Rett syndrome. She had normal development till the age of 2 years. However, over the next 4–5 months, she lost her acquired, purposeful hand skills; expressive and receptive language; and reciprocal social interaction; and gradually developed a broad-based gait and typical midline stereotyped hand movements (mouthing, rubbing).

Rett症候群女児における手の常同運動の"休止"を導いた場面条件とその要因 : 事例研究

本研究は、8歳のRett症候群女児における手の常同運動の"休止"を分析したものである。ここで休止とは、下記の取り組み場面で、非常に顕著な手の常同運動が一時的にみられなくなる状態のことである。設定した場面は次の通りである。すなわち、(1)本児は、プッシュ式スイッチが取り付けられ外部動力により動く車椅子に座っている。(2)常同運動を行っていた右手をスイッチのほうに伸ばしてそれを押す動作は、毎回、援助者によりガイドされるが、車椅子が動きはじめて数〜数十秒後にはガイドの手が離され、本児単独でスイッチの上に手を乗せている状態、すなわち、常同運動が休止している状態となる。この休止(1秒以上)は、計8セッションの取り組み全体において185回観察され、最長時間は8分に達した。休止の持続時間を5つの活動水準に基づいて分類した結果、休止を導いた主要因は、移動に伴う環境変化への視覚的注意と身体的・精神的弛緩状態であると考えられた。

¿Se puede atribuir el fenotipo conductual del Síndrome X Frágil al retraso mental y al trastorno por déficit de atención/hiperactividad?

Fragile X syndrome (FXS) reveals itself as dysmorphic stigmata, systemic manifestations, neurological symptoms and cognitive-behavioural manifestations. Mental retardation (MR) and attention deficit hyperactivity disorder (ADHD) nearly always appear as examples of this last case, but most patients also present a series of fairly common behavioural characteristics. The most characteristic types of conduct seen in FXS include: language problems, lack of attention, hyperactivity, anxiety, shyness, behavioural problems, stereotypical hand flapping, gaze aversion, obstinacy and aggressiveness.The purpose of this work is to determine which behavioural aspects of the syndrome are linked to the genetic specificity and are not, therefore, determined by MR and ADHD.Three groups of patients were compared: 30 children diagnosed as suffering from FXS, 30 children with MR caused by diverse aetiologies and 323 children diagnosed as suffering from ADHD.It was found that there were no significant differences between the IQ and the age of the FXS and MR groups. To determine the behavioural characteristics of the three groups the parents of the patients answered Achenbach's CBCL/4-18 survey.The results obtained show that certain types of conduct that are very typical of FXS are represented significantly more frequently in the FXS group than in the groups of patients with MR and ADHD. This behaviour includes: timidity, attachment to adults, shyness, repetition of certain actions over and over again, pronunciation and speech problems, fear of animals, situations or places, and concern for tidiness and cleanliness. These findings lend support to the idea that the behavioural phenotype of FXS is linked to the genetic disorder and is not, therefore, a consequence of MR or ADHD.

Pathophysiology of Rett syndrome from the stand point of clinical characteristics

In this report, we reviewed the characteristics of motor development and motor symptoms of Rett Syndrome (RTT) and demarcated the early and pathognomonic motor symptom which correlates to the impairment of the higher cortical function (HCF) assessed by the ability of language. It is suggested that failure of locomotion in late infancy is the primary and pathognomonic symptom. Thus, the impairment of the neurons or neuronal systems involving locomotion is suggested as the primary lesion in the pathophysiology of RTT not only for motor dysfunction but also for the failure in the development of language and cognitive function. On the other hand the neuronal systems involving the loss of purposeful hand use and the stereotyped hand movement, the most characteristic and diagnostic symptoms of RTT appearing in early childhood, are affected later or secondarily but induce further degradation of the HCF. Hypofunction of the aminergic neurons in the brainstem and midbrain is suggested as the cause of dysfunction of these neuronal systems, for those of locomotion, the noradrenarlin (NA) and/or the serotonin (5HT) neurons and for the stereotyped hand movement the dopamine (DA) neurons. The NA and/or the 5HT neurons in the brain stem may be involved primarily and may cause dysfunction of the midbrain DA neuron directly or indirectly through affecting the pedunculopontine nuclei.

Lamotrigine in two cases of Rett syndrome

Rett syndrome (RS) is a particular neurodevelopmental disorder in which symptoms develop in early infancy and manifests particular symptoms at certain ages. Two girls aged 4.5 and 2.5-years-old were admitted with complaints of seizures, regression of language, psychomotor development, and autistic behavior. They had fulfilled the criteria of classic RS. Lamotrigine was used in the treatment of the convulsions. After lamotrigine therapy, the convulsions were successfully controlled and the stereotyped hand movements and autistic behaviors markedly decreased. We would like to stress that, aside from convulsion, abnormal signs of the syndrome such as stereotyped hand movements and autistic behaviors might also be improved with lamotrigine, but detailed and controlled studies should be performed to identify whether lamotrigine has any positive effects in RS.

MECP2 mutations in Danish patients with Rett syndrome: high frequency of mutations but no consistent correlations with clinical severity or with the X chromosome inactivation pattern.

Rett syndrome (RTT) is a neurodevelopmental disorder, which almost exclusively affects girls, who, after an initial period of apparently normal development, display gradual loss of speech and purposeful hand use, gait abnormalities and stereotypical hand movements. In the year 2000, mutations in the gene for the methyl CpG binding protein 2, MECP2, have been identified in 35-80% of the patients in three different studies. We have identified 15 different MECP2 mutations in 26 of 30 Danish RTT patients. The mutations included five novel mutations (one point mutation, three smaller deletions involving identical regions in the gene, and one duplication). In contrast to the point mutations and the duplication, which all affect the methyl binding domain or the transcriptional repressing domain, the three overlapping deletions are clustered in the 3' end of the gene. We found no consistent correlation between the type of mutation and the clinical presentation of the patient or the X-inactivation pattern in peripheral blood. Our high mutation detection rate, compared to two of the previous studies, underscores the importance of the inclusion criteria of the patients and supports that MECP2 is the most important, if not the only, gene responsible for RTT.

Parametric Analysis of Overcorrection Duration Effects

Positive practice overcorrection (PPOC) has long played a significant role in the behavioral treatment of serious self-stimulatory behavior. Three experiments comparing the effectiveness of 30-second, 2-minute, and 8-minute PPOC on reduction of stereotypic hand behavior of adults with severe to profound developmental disabilities were conducted to resolve inconsistencies in previously reported findings concerning the role of PPOC duration in response suppression. Experiment 1, which used an alternating treatments--multiple baseline design, suggested that the different durations were equally effective in reducing the stereotypic behaviors to near-zero levels. Experiment 2, which used a reversal design, supported the findings of Experiment 1. Experiment 3, which used a reversal design to test the shortest and longest durations, generally confirmed the results of the first two experiments. This study therefore failed to support the oft-claimed superiority of long-duration PPOC. The possible factors underlying these findings and their implications for future research and practice are discussed.

Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.

Rett syndrome (RTT, MIM 312750) is a progressive neurodevelopmental disorder and one of the most common causes of mental retardation in females, with an incidence of 1 in 10,000-15,000 (ref. 2). Patients with classic RTT appear to develop normally until 6-18 months of age, then gradually lose speech and purposeful hand use, and develop microcephaly, seizures, autism, ataxia, intermittent hyperventilation and stereotypic hand movements. After initial regression, the condition stabilizes and patients usually survive into adulthood. As RTT occurs almost exclusively in females, it has been proposed that RTT is caused by an X-linked dominant mutation with lethality in hemizygous males. Previous exclusion mapping studies using RTT families mapped the locus to Xq28 (refs 6,9,10,11). Using a systematic gene screening approach, we have identified mutations in the gene (MECP2 ) encoding X-linked methyl-CpG-binding protein 2 (MeCP2) as the cause of some cases of RTT. MeCP2 selectively binds CpG dinucleotides in the mammalian genome and mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A (refs 12,13). In 5 of 21 sporadic patients, we found 3 de novo missense mutations in the region encoding the highly conserved methyl-binding domain (MBD) as well as a de novo frameshift and a de novo nonsense mutation, both of which disrupt the transcription repression domain (TRD). In two affected half-sisters of a RTT family, we found segregation of an additional missense mutation not detected in their obligate carrier mother. This suggests that the mother is a germline mosaic for this mutation. Our study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.

Altered Development of Glutamate and GABA Receptors in the Basal Ganglia of Girls with Rett Syndrome

Rett syndrome (RS), a genetic disorder found almost exclusively in females, is associated with psychomotor regression and stereotyped hand movements. To determine whether a defect in basal ganglia amino acid neurotransmission plays a role in RS, NMDA-, AMPA-, kainate (KA)-, and metabotropic (mGluR)-type glutamate receptors (GluRs) and GABA receptors were labeled autoradiographically in the caudate, putamen, and globus pallidus of postmortem brain slices from 9 RS girls and 10 age-related controls. The cases were divided into younger (8 years or younger) and older age groups to study age-related changes in receptor binding density. We found significant reductions in AMPA and NMDA receptor density in the putamen and in KA receptor density in the caudate of older RS cases compared to controls. In contrast, mGluR density in the basal ganglia of RS patients was not altered significantly. The density of GluRs in control subjects generally showed more limited changes with age than in RS cases. In contrast to ionotropic GluRs, GABA receptor density was significantly increased in the caudate of young RS patients. The effects on GluR density in the putamen, which serves a primary motor function, were consistent with the motor deficits observed in RS, while those on amino acid transmitter receptors in the caudate may account for some cognitive features. Our studies demonstrate regional, receptor-subtype, and age-specific alterations in amino acid neurotransmitter receptors in the basal ganglia of RS girls. These changes may correlate with age-related clinical stages observed in RS.

Movement dysfunction following repetitive hand opening and closing: anatomical analysis in Owl monkeys.

Repetitive strain injuries are thought to result from biomechanical stress and tissue microtrauma. The purpose of this study was to investigate the presence of local inflammation, scarring or anatomical variations of the flexor tendons and the median and ulnar nerves in four Owl monkeys behaviorally trained at a repetitive motor or sensory task. Three monkeys were trained to repetitively open and close a handpiece. The two monkeys that used rapid, stereotypical hand squeezing developed a task-specific movement dysfunction (one in 5 weeks and one in 24 weeks). The third monkey used a variable shoulder-pulling strategy and did not develop movement problems. The fourth monkey served as a control subject for the repetitive motor movements, trained on a repetitive sensory task, and did not develop a task-specific movement dysfunction. On dissection and histologic staining, there were no signs of active inflammation in the median nerve, the ulnar nerve, or the flexor tendons in any of the monkeys. However, the monkey that developed movement problems after 5 weeks of repetitive hand squeezing had an anatomical restriction of the flexor profundus tendon on the fourth digit of the trained side and the third digit of the untrained side. Reorganization of the representation of the hand on the contralateral somatosensory cortex (area 3b) was noted in the two monkeys that developed motor control problems and in the monkey performing the repetitive sensory task. These findings suggest that repetitive, stereotypical motor behaviors can lead to motor control problems without local signs of tendon or nerve inflammation. Preexisting anatomical restrictions may modify the time course for the development of movement dysfunction under conditions of stressful repetition. This animal model may simulate clinical focal hand dystonia (or occupational hand cramps) which can develop in human subjects who perform prolonged, repetitive, stereotypical movements.

Familial aggregation in Rett syndrome: what is the evidence for clustering of other disorders in families of affected girls?

Rett syndrome is a neurodevelopmental disorder of unknown cause which affects girls almost exclusively. Apparently normal development in the first year of life is usually followed by loss of skills and the development of stereotypic hand movements. This study has used genetic epidemiological methods including a case control design to examine the evidence for aggregation of other disorders in families of girls with Rett syndrome. In one family there were two sisters with a condition consistent with Rett syndrome. Intellectual disability was not reported more commonly in case families (P = 0.46). However, "learning problems" were slightly commoner (P = 0.05) especially in the parental generation (P = 0.02) and these findings warrant further investigation. Mental illness and seizures were not reported at an increased prevalence. However, we would recommend the use of other strategies to collect information about psychiatric illness. Spinal curvature was reported more commonly in case families (P = 0.07) but no mechanism for clinical verification of this was included in the study. There was an apparent increase in bowel problems in the parents (P = 0.04). The major weaknesses of our study were our inability to validate any diagnosis clinically and the lack of power (due to the comparative rarity of the outcomes). The strengths are that we have been able to collect pedigree data on the families of a substantial proportion of a total population of girls with Rett syndrome and to collect comparative data from a control population. Our reported findings warrant further investigation in a larger study.

Effects of amount and type of social interaction/activity on stereotyped hand mannerisms in individuals with Rett Syndrome

Stereotyped hand mannerisms are a defining characteristic of Rett syndrome. This study examined the effects of social interaction/activity on the frequency of stereotyped hand mannerisms in seven individuals with Rett syndrome. The percentage of 15 s intervals with stereotyped hand mannerisms was recorded during repeated 10 min sessions under two conditions in an ABAB reversal design. The High Social Interaction/ Activity condition occurred during a mealtime when the individuals also received high levels of social interaction from a staff person. In the second, Low Social Interaction condition, a staff person was present but did not interact with the individual and no activities were presented. The trend was for more Stereotypic hand movement in the Low Social Interaction/Activity condition. However, there was a considerable amount of individual and within condition variability. The results suggest a need for individual assessment in order to develop educational interventions to attenuate stereotyped hand...

Effects of Amount and Type of Social Interaction/Activity on Stereotyped Hand Mannerisms in Individuals with Rett Syndrome

Stereotyped hand mannerisms are a defining characteristic of Rett syndrome. This study examined the effects of social interaction/activity on the frequency of stereotyped hand mannerisms in seven individuals with Rett syndrome. The percentage of 15 s intervals with stereotyped hand mannerisms was recorded during repeated 10 min sessions under two conditions in an ABAB reversal design. The High Social Interaction/Activity condition occurred during a mealtime when the individuals also received high levels of social interaction from a staff person. In the second, Low Social Interaction condition, a staff person was present but did not interact with the individual and no activities were presented. The trend was for more Stereotypic hand movement in the Low Social Interaction/Activity condition. However, there was a considerable amount of individual and within condition variability. The results suggest a need for individual assessment in order to develop educational interventions to attenuate stereotyped hand mannerisms in persons with Rett syndrome.

Japanese monozygotic twins with Rett syndrome

We present a study of 28-year-old Japanese monozygotic female twins with Rett syndrome (RS). To our knowledge, this is the first report of monozygotic twins with RS from Japanese family. There are some differences between twins about seizures, scoliosis and stereotypical hand movements during adolescence. Monozygosity was confirmed by both blood typing and HLA titers.

Focus on Practice: The Relevance and Value of Music Therapy for Children with Rett Syndrome

Rett syndrome was first described in 1966 by Andreas Rett and, to date, has only been reported in girls. It is characterised by normal development from 6 to 18 months followed by a progressive loss of motor and cognitive skills and the development of stereotyped hand movements. Girls with Rett syndrome appear to be responsive to music. Using case study material Sarah Hill, a music therapist at a special school in Surrey, shows the value and relevance of music therapy.

Behavioral competition in a case of Rett syndrome

Major behavioral features of Rett syndrome are the loss of instrumental reaching and grasping and the presentation of some variant of hand-hand or hand-mouth stereotypy. As part of an experimental home intervention program, a 3-year-old girl with Rett syndrome was exposed to four types of contingency games designed to elicit instrumental reaching, kicking, vocalization, and eye movement, respectively. Parent and subject performance were videorecorded on seven occasions over the initial 2-month period. Evaluation of these records provided evidence of contingency learning in all but the vocalization games. Stereotypic hand clasping was examined in relation to the performance of instrumental behavior (reaching, kicking, looking). Coincidental (short-term mutual inhibition arising by chance co-occurrence), associative (short-term mutual inhibition arising by having elicitor in common), and foundational (long-term mutual inhibition arising by having neural network in common) forms of specific behavioral competition were defined and examined. Evidence for coincidental and foundational competition was found in the relation between reaching and hand clasping. Implications for the support of functional hand use are discussed.

Upper-limb Postures and Movements during Diamond Polishing.

Previous occupational health studies of diamond polishers have identified high rates of musculoskeletal disorders of the hands and arms in this population, specifically, ulnar neuropathy in the right elbow. These disorders may be due to the repetitive and forceful motions of the upper extremity required to manipulate the hand-held polishing tools. A video-based, biomechanical analysis of the upper extremities of polishers at several diamond-processing factories in Israel was conducted. Detailed motion measurements of the wrists, elbows, and shoulders of polishers were made while the subjects performed their usual work. During a typical workday, the basic polishing cycle, which involves a series of stereotyped hand and arm movements, is repeated more than 5,000 times. Sustained, extreme flexion of the right elbow, which is the arm holding the eyepiece, may account for the higher rates of ulnar neuropathy in this extremity.

Rett syndrome: Controlled study of an oral opiate antagonist, naltrexone

The opiate antagonist, naltrexone, will be beneficial in Rett syndrome. Twenty-five individuals fulfilling the criteria for Rett syndrome. Randomized, double-blind, placebo-controlled crossover trial with two treatment periods, 4 months each, and an intervening 1-month washout period. Clinical stage, motor and cognitive development, motor-behavioral analysis, neurophysiological parameters (computerized electroencephalographic analysis, breathing characteristics, quantification of stereotyped hand movements, and sleep characteristics), and cerebrospinal fluid beta-endorphin measurements were evaluated at baseline and at the end of each treatment period. Only data from the first period of this study were analyzed due to significant sequence effects in the crossover design. This analysis indicated positive effects on certain respiratory characteristics including decreased disorganized breathing during wakefulness. Four (40%) of the individuals receiving naltrexone progressed one or more clinical stages versus none of the individuals receiving placebo. The adjusted (for baseline value and Rett stage) end of treatment psychomotor test age (Bayley Scales) was significantly higher for the placebo group. There was no significant change for the other parameters. Naltrexone may modify some of the respiratory disturbance in Rett syndrome. Declines in motor function and more rapid progression of the disorder suggest a deleterious effect.

ビデオフィードバック訓練によるRett症候群児の手の自発動作形成と常同運動に及ぼす効果

本研究の目的は、1名のRett症候群児の手の常同運動に及ぼすビデオフィードバック訓練の効果を検討することである。ビデオフィードバックシステムは、タッチセンサプレートとVTRからなり、それらはマイクロコンピューターに接続された。訓練条件は3条件;(1)援助なし、(2)援助あり左腕手自由、(3)援助あり左腕補助であった。被験児は、手でプレートに触り、TVをつけるように求められた。その結果、徐々に援助なしでプレートを触ることができるようになり、それにつれて手の常同運動は減少した。左腕補助の効果は常同運動が頻繁に生起していた時のみみられた。次に、反転試行が実施され、タッチ動作は顕著に減少した。再び援助なし試行になると、タッチ動作は復帰した。また、訓練セッションでは、タッチ動作のパターンが変容していった。これらの結果から、ビデオフィードバック訓練はRett症候群児の手の常同運動に効果的な指導法である可能性が示唆された。

Case study: Noninvasive behavioral treatment of self‐injurious hand stereotypy in a child with Rett syndrome

AbstractTreatment of stereotypic hand mouthing in a 3‐year‐old girl with Rett syndrome by differential reinforcement of competing functional responses plus response interruption is described and evaluated in this case study. A package of graduated guidance with social and edible reinforcers successfully established stable rates of functional hand movements to activate toys, gross motor responses to verbal prompts, palmar grasp and release, and some vocal imitation. Contingent response interruption virtually eliminated hand mouthing during instructional sessions. Instruction alone did not maintain hand mouthing suppression when interruption was withdrawn, and treatment gains appeared highly discriminated. Post‐hoc comparison indicated differential reinforcement plus response interruption (DR1 + 1) to be superior to hand splints in reducing hand stereotypies, with approximately equivalent increases in collateral tongue thrusting.