Gross motor ability in Rett syndrome--the power of expectation, motivation and planning.

A main task for the physiotherapist at the Swedish Rett Center is to document and report successful treatment. This report shows the possibility to regain function, get variation and avoid contractures for several years. A thorough neurologic, orthopaedic and physiotherapeutic assessment and analysis is essential. We stress the importance of keeping the feet in good position, using surgery and well fitting orthoses when needed, making standing possible and for some persons, walking. For the effect of treatment the following factors were of vital importance: the expectations of the persons treating the girl/woman - what they believed she could do, the motivation of the girl/woman herself, a joint plan for intervention including everyone involved, and well educated personnel, well informed about Rett syndrome--its problems and possibilities.

Head growth in Rett syndrome.

The longitudinal development of head growth was investigated in girls with Rett syndrome (RS). Growth retardation was expressed in standard deviation (SD) scores. In classic types, the mean head circumference fell successively to 2 SD scores below the norm at the age of 4 years. After the age of 8 it stabilized close to -3 SD scores. In forme fruste variants, the mean head circumference was within normal limits; however, it was significantly below the norm, -0.8 SD scores. In girls with classic RS, head growth had decelerated by less than 1 SD score in 20% of the girls at the age of 6 years and in 10% at the age of 12 years. In forme fruste variants only a small decline in head growth occurred. Head growth decline may thus be very small in classic RS and is usually not present at all in forme fruste variants. In the future, it should, therefore, neither be regarded as a necessary diagnostic criterion for classic RS, nor as a valid one for forme fruste variants.

Occurrence of Rett syndrome in boys.

The neurologic disorder Rett syndrome was originally described exclusively in girls. We present two boys with clinical features of Rett syndrome. Other than head circumference deceleration, no longer considered mandatory, patient 1 meets all of the criteria. Using fluorescent in situ hybridization analysis, 97.6% of cells were found to be karyotypically normal (46,XY). No mutation was detected on screening of the coding region of the MECP2 gene. The second patient also has classic features of Rett syndrome. However, cytogenetic analysis of peripheral blood revealed a karyotype 47,XXY[23]/46,XY[7] confirming mosaicism for Klinefelter's syndrome. A T158M missense mutation in the methylcytosine-binding domain of the MECP2 gene was identified. A diagnostic bias against the clinical identification of Rett syndrome in boys may exist. This presentation of the male phenotype could be more common than it would appear, although boys with MECP2 mutations might also manifest in other ways. Rett syndrome remains a clinical diagnosis that should not be dismissed in boys, and thorough evaluation including karyotype and mutation testing is warranted.

Characterisation of breathing and associated central autonomic dysfunction in the Rett disorder.

AIM: To investigate breathing rhythm and brain stem autonomic control in patients with Rett disorder. SETTING: Two university teaching hospitals in the United Kingdom and the Rett Centre, Sweden. PATIENTS: 56 female patients with Rett disorder, aged 2-35 years; 11 controls aged 5-28 years. DESIGN: One hour recordings of breathing movement, blood pressure, ECG R-R interval, heart rate, transcutaneous blood gases, cardiac vagal tone, and cardiac sensitivity to baroreflex measured on-line with synchronous EEG and video. Breathing rhythms were analysed in 47 cases. RESULTS: Respiratory rhythm was normal during sleep and abnormal in the waking state. Forced and apneustic breathing were prominent among 5-10 year olds, and Valsalva breathing in the over 18 year olds, who were also most likely to breathe normally. Inadequate breathing peaked among 10-18 year olds. Inadequate and exaggerated breathing was associated with vacant spells. Resting cardiac vagal tone and cardiac sensitivity to baroreflex were reduced. CONCLUSIONS: Labile respiratory rhythms and poor integrative inhibition in Rett disorder suggest brain immaturity. Linking this to an early monoaminergic defect suggests possible targets for the MECP2 gene in clinical intervention. Exaggerated and inadequate autonomic responses may contribute to sudden death.

Guidelines for reporting clinical features in cases with MECP2 mutations.

An international group recommends that papers relating phenotypes to genotypes involving mutations in the X chromosome gene MECP2 should provide a minimum data set reporting the range of disturbances frequently encountered in Rett Syndrome. A simple scoring system is suggested which will facilitate comparison among the various clinical profiles. Features are described which should prompt screening for MECP2 mutations.

Rett syndrome: potential gene sources--phenotypical variability.

A previous genealogic study on classical Swedish Rett syndrome (RS) females documented an increased rate of common ancestry, with a high percentage originating generations ago in the same homestead. The present study, an a priori test of the first study, examines an additional 20 RS females, who were consecutively traced. Of these, no fewer than 10/19 (53%) originated from earlier defined "Rett areas": 11/19 (58%) could even be traced to the same homestead. In two clusters, each consisting of three RS females, all six subjects were descendants of the same two couples several generations ago. Consanguineous marriages among grandparents on both sides were found to have occurred in 11% (4/37), i.e. significantly more frequently than in the average Swedish population (1%). The results of this second study confirm all points of the first. A clinical analysis of cases with common ancestral origin underlines the phenotypical variability which is often seen in interrelated RS females. We conclude that RS can appear in either its classical form or as a variant. Our genealogical data may indicate transmission starting with a premutation that over generations can result in a full mutation, probably when the parents have the premutation in a homozygous form.

Gross motor disability and head growth in Rett syndrome--a preliminary report.

Growth of head circumference was measured in 99 RS girls and compared to gross motor function. The degree of head growth deceleration correlated to the severity of gross motor disability at 12 years of age.

Rett syndrome: the late infantile regression period--a retrospective analysis of 91 cases.

The late infantile regression period of Rett syndrome was analysed in a consecutively collected series of females, born 1945-87 (median 17 1/2 years), fulfilling the diagnostic criteria for classic Rett syndrome. For general information, data from 91 girls and women were used (group A), while more detailed analysis was based on the youngest 20, all born during the last decade (group B). Median ages at onset of developmental stagnation (stage I) were 11 (5-24) and 10 (5-18) months for groups A and B, respectively. Loss of acquired skills (stage II) began at 19 (12-36) and 17 (13-25) months, and lasted for 19 (2-53) and 13 (2-32) months. Onset of the period of loss was distinctly marked in 43%, dramatic in 16% and insidious in 41%. Gross motor delay and aberrant behaviour raised the first suspicions of disease, while a more specific pattern comprising a triad of manifestations, i.e. contact/communication, hand use/skill, babble/words, characterized the loss of acquired skills. Although development invariability came to a definite break at a crucial stage of maturation, an "awakening" (stage III) and return of interest to act and interact astonishingly followed the period of withdrawal. Apraxia was found in all, but some use of the hands could be enticed in engaging and non-demanding situations. The observed preference for use of the left hand (9/11), compared to the right (2/11), suggested a reflection of an underlying dysfunction/disease process, also displayed as spike activity in left central leads in EEGs from 13/20 girls.

Rett syndrome: a search for gene sources.

A series of 77 Swedish females with classical Rett syndrome were genealogically traced as far back as possible, in most cases to 1720-1750, or 7-10 generations. Details were collected concerning approximately 8,000 ancestors. Common ancestry was seen in 2 pairs of females with Rett syndrome. Thirty-nine of the 77 Rett females were traced to 9 small and separate rural areas, and 17 pairs even came from the same farm or homestead. The common origin was found equally often among descendants of the father as of the mother. In 9 cases, the father came from one and the mother from another of the 9 specific "Rett areas." These observations, combined with the finding of a raised rate of consanguineous marriages in the paternal as well as in the maternal ancestry, point to a genetic transmission. Analyses of parental ages at birth and of birth order gave normal results.

Rett syndrome in Sweden. Neurodevelopment--disability--pathophysiology.

Rett syndrome (RS), a complex and severely disabling neuromotor disorder affecting young girls, was not internationally recognized until in the middle eighties. In Austria and Sweden only, there are clinical experiences since the sixties. The aims of this study were to 1) define the nucleus group of RS in Sweden, 2) develop a frame of defined stages for describing the clinical progress of disease, 3) identify early developmental patterns and their predictivity, 4) give the natural history of neuromotor impairments and disability in adults, 5) analyse the period of clinical regression as to developmental profiles, patterns and progression of symptoms, 6) search informative neurophysiologic correlates to clinical symptoms and signs. By a 6 year (1984-90), nationwide search procedure, comprising an information and tracing program, a travelling consultant program, and a neuropediatric and laboratory examination program, 88 females were added to those 17, observed in Sweden during the sixties and seventies. By March, 1990, 105 females, aged 19 months-44 years (median 17 1/2 years), had entered this series, which was considered representative for the nucleus group of RS in Sweden. 97/105 females (92.3%) fulfilled the criteria for classic RS, according to internationally accepted clinical criteria, and 8 (7.7%), represented so called "formes frustes". The prevalence for classic RS in the south-west region of Sweden was 1:12.000-13.000 girls, the birth years 1965-76 and 1960-84. Based on 29 females with RS, aged 13-28 years, a clinical staging system was constructed and evaluated in 1985, emphasizing the main different phases of the disorder throughout life. This staging system was found a valuable tool for clinical assessment, documentation, and research approach, and has become internationally accepted and widely used. Further experiences have given rise to minor adjustments, which are proposed. By scrutinizing early documentation from 10 girls, at referral aged 20 months-6 1/4 years (median 3 1/4 years) and retrospectively applying the Denver Developmental Screening Test frames, early achievements, signs and symptoms were reconstructed in 1986. Although characteristic neuromotor and neurobehavioural patterns of help for early suspicion, and even subtle signs, possibly reflecting a disorder already during the first months of life, could be identified, predictive clinical manifestations of diagnostic value were not found.(ABSTRACT TRUNCATED AT 400 WORDS)