Loss Of Purposeful Hand Use Research Articles

A circuit-level biomarker of Rett syndrome based on ectopic phase-amplitude coupling during slow-wave-sleep.

Rett syndrome (RTT) is a neurodevelopmental disorder characterized by loss of purposeful hand use and spoken language following an initial period of normal development. Although much is known about the genetic and molecular underpinnings of RTT, less is known about the circuit-level etiopathology. Coupling of oscillations during slow-wave-sleep (SWS) underlies important neurocognitive processes in adulthood, yet its emergence has yet to be described in early typical development (TD) or in RTT. We therefore addressed these unknowns by describing SWS cross-frequency coupling in both RTT and early TD using a retrospective study design. We found that in TD, phase-amplitude coupling (PAC) during SWS was dominated by coupling of slow-wave (0.5-2Hz) phase to theta amplitude (5-8Hz, "SW:T") as well as slow-wave to spindle-range (12-15Hz, "SW:S"). Coupling exhibited characteristic vertex-prominent spatial topography, which emerged during an early developmental window. This topography failed to develop in patients with RTT due to persistent ectopic coupling. Furthermore, we found that subtypes of RTT exhibit distinct PAC topographic profiles, and that ectopic PAC correlates with clinical severity. These findings suggest that altered PAC dynamics and spatial organization during SWS may underlie the circuit-level pathophysiology of RTT and suggest that ectopic coupling may contribute to RTT pathogenesis.

Meaningful word acquisition is associated with walking ability over 10 years in Rett syndrome

PurposeTo investigate walking ability in Japanese patients with Rett syndrome (RTT). MethodsWalking ability was assessed in 100 female Japanese patients with RTT using univariate and multivariate analysis in all age groups, and in patients over 10 years of age. We analyzed walking ability and confounding factors including prenatal-perinatal histories, developmental milestones, somatic and head growth, anthropometric data, body mass index, age of loss of purposeful hand use, age at onset of stereotypic hand movement, history of autistic behavior, age at regression, presence or absence of seizures, and the results of MECP2 genetic examination from the Japanese Rett syndrome database. ResultsUnivariate analysis revealed that acquisition of walking in all age groups was significantly correlated with the acquisition of meaningful words, microcephaly, and crawling (P < 0.0001, P = 0.005, P < 0.0001, respectively). Univariate analysis revealed that walking ability over 10 years of age was significantly correlated with acquisition of meaningful words, microcephaly, and body mass index (P < 0,0001, P = 0.005, P = 0.0018, respectively). MECP2 mutations R306C, R133C, and R294X were significantly associated with different acquisition of crawling (P = 0.004) and walking (P = 0.01). Multivariate analysis revealed that only acquisition of meaningful words was significantly correlated with walking ability over 10 years of age. This trend excluded the genetic effects of R306C, R133C, and R294X. ConclusionsMeaningful word acquisition was robustly associated with walking ability over 10 years. Prognosis of walking ability may be predicted by the acquisition of meaningful words. This information is potentially useful for early intervention and the planning of comprehensive treatment for young children with RTT.

Rett syndrome: a neurodevelopmental disorder

Rett Syndrome is a rare genetic disorder caused by a mutation on the MECP2 gene on the X chromosome. It classically presents with neuroregression, loss of purposeful hand use, stereotypical involuntary hand wringing movements, an ataxic gait and acquired microcephaly with a large proportion of patients developing seizures. The authors present the case of a 3.5 year old girl with severe global developmental delay and regression, loss of purposeful hand use and an ataxic gait for 2 years and seizures since 5 days along with microcephaly with involuntary hand movements but no classic wringing movements with no significant findings on MRI and EEG and diagnosed with Rett Syndrome on the basis of genetic testing.

Professor Jean Aicardi

Professor Jean Aicardi

P193 – 2860: Many faces of Rett syndrome: Is there still a diagnostic delay?

Objective Rett syndrome is the second most common neurodevelopmental genetic disorder in girls. Major clinical features include developmental regression after a normal period of development, autistic behavior, loss of purposeful hand use, stereotypical hand movements, abnormal breathing pattern, peripheral vasomotor disturbances and seizures. MECP2 gene mutations can be detected in up to 90–95% of patients with classical Rett syndrome. Methods In order to document the clinical course in this syndrome, we have included 15 consecutive patients in whom MECP2 mutations were detected. Results Age range was 3–22 years (median 15 years). First admission to a physician with a suspicion of abnormal development was between 8 months to 4 years. Diagnostic delay on the bedside was calculated as median 1 year (0–3.5 years). Stereotypical hand movements developed between 8 months – 5 years (median 2 years). One patient did not have normal early developmental milestones. Loss of purposeful hand movements was seen between 1–9 years (median 2 years). Of note, in one patient loss occurred at 9 years of age and in another 3-year-old, purposeful hand use was never observed. Microcephaly was detected in 12 patients. During a mean course of 5.7 years (2 months to 18 years), two of the patients lost independent ambulation (6 and 10 years). Other than stereotypical hand movements 5 patients had additional stereotypies including pelvic tilt, truncal rocking motion and spitting behavior. Conclusion Despite recent availability of MECP2 testing, there is still a considerable delay in diagnosis, due to clinical variability in terms of appearance of core symptoms and course.

Rett syndrome: individual differences in developmental and behavioral markers and psychosocial stress

Rett Syndrome is a severe neurological developmental disorder caused by a genetic mutation on the long arm of the X chromosome (Xq28). This disorder is characterized by a loss of purposeful hand use, verbal language, and specific behaviors. Data were obtained from a survey of the parents of 83 girls on pre-verbal skills (Pre-verbal Communication Schedule), behavioral characteristics and emotional expression (Rett Syndrome Behaviour Questionnaire) and on maternal psychosocial stress (Handicap-related Problems for Parents Inventory). There is considerable individual variability in the developmental and behavioral characteristics which is not explained as a function of age. Maternal stress correlates with the daughters' mood, anxious reactions and night-time behaviors. Some implications for diagnosis and family counseling are discussed.

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.

Molecular genetics of Rett syndrome

Rett syndrome is a neurodevelopmental disorder affecting almost exclusively females. It affects approximately one in 15 000 females and is characterized by a loss of purposeful hand use, autism, ataxia and seizure. The disorder is usually sporadic, but rare familial cases have also been reported. Recently it has been shown that familial cases are an X-linked dominant disorder and the disease locus maps to Xq28. A candidate gene called methyl-CpG-binding protein 2 was identified from the Xq28 region and was shown to contain mutations in about 77% of Rett syndrome patients. Since the encoded protein was previously shown to be a global transcriptional repressor, undesired expression of yet unidentified genes that are normally repressed is considered to be pathogenic in Rett syndrome.

Rett syndrome: A longitudinal developmental case report

Rett syndrome is a recently described progressive neurological disorder of unknown etiology occurring only in females, causing severe to profound mental retardation and characterized by loss of purposeful hand use and stereotypic hand movements. The present study examined development in five areas: gross motor skills, fine motor skills, self-help skills, communication, and cognition. Results indicated a general stagnation in all developmental areas beginning at approximately 15 months. No skills progressed beyond the 2-year level; this, despite several years of intensive, interdisciplinary intervention. Cognitive and communication skills regressed, then stabilized for several years, and subsequently began further regression. Gross motor and self-help skills appear to be areas of relative strength.

A Progressive Syndrome of Autism, Dementia, Ataxia, and Loss of Purposeful Hand Use in Girls: Rett Syndrome

A Progressive Syndrome of Autism, Dementia, Ataxia, and Loss of Purposeful Hand Use in Girls: Rett Syndrome

A case of the rett syndrome

This is a case report of the Rett syndrome in a girl with normal general and psychomotor development during the first 12 mos. Afterwards developmental stagnation and retrogression appeared which led within one yr to dementia, autism, loss of purposeful hand use, truncal ataxia and apraxia of gait. Characteristic stereotypic movements of the hands occurred, and, furthermore, rhythmic truncal balancing and episodic hyperpnea. At 2 yrs, neurological examination showed slight hypertonia and hyperreflexia of the legs without extensor plantar signs, there was relative microcephaly, and visceral examination was normal. The diagnosis was made on the basis of clinical signs: all laboratory investigations were negative except EEG which showed unspecific modifications. We didn't find hyperammonemia. No progression of the symptoms appeared in the 15 mos following the diagnosis.

A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases.

Thirty-five patients, exclusively girls, from three countries had a uniform and striking progressive encephalopathy. After normal general and psychomotor development up to the age of 7 to 18 months, developmental stagnation occurred, followed by rapid deterioration of higher brain functions. Within one-and-a-half years this deterioration led to severe dementia, autism, loss of purposeful use of the hands, jerky truncal ataxia, and acquired microcephaly. The destructive stage was followed by apparent stability lasting through decades. Additional insidious neurological abnormalities supervened, mainly spastic parapareses, vasomotor disturbances of the lower limbs, and epilepsy. Prior extensive laboratory investigations have not revealed the cause. The condition is similar to a virtually overlooked syndrome described by Rett in the German literature. The exclusive involvement of females, correlated with findings in family data analyses, suggests a dominant mutation on one X chromosome that results in affected girls and nonviable male hemizygous conceptuses.