Developmental and behavioural disturbances in 13 boys with fragile X syndrome

Developmental and behavioural aspects were studied in 13 boys aged 2.6–12.5 years from three families with the fragile X syndrome. The following observations were made. (1) Moderate to severe retardation was present in all boys; non-verbal IQs ranged between 25 and 67 (mean 46±14); IQ and age were negatively correlated (P<0.01). (2) Language development was grossly delayed in all boys: most had severe articulation problems. (3) Imitative and symbolic play (e.g. doll play) were strikingly retarded as compared to abstract play (e.g. block design). (4) Autistic features such as no use of eye contact, stereotyped movements and echolalia were found in 9/13 boys; the same number showed aggressive behaviour. (5) General activity was reduced during the 1st year of life; most boys became very hyperactive during the second year; and short attention span and increased distractability were observed in all. (6) Motor development was mildly delayed; all boys were clumsy and moderately hypotonic. The fragile X syndrome ought to be considered in retarded boys with a dissociated developmental pattern, in particular a striking delay in language and play development, and autistic features

The fragile X syndrome (Martin-Bell syndrome). Clinical and cytogenetic findings in 16 prepubertal boys and in 4 of their 5 families

Clinical and cytogenetic findings from 16 prepubertal males with the fragile X syndrome (X-linked mental retardation with postpubertal macro-orchidism and fragile site at Xq27/8, or Martin-Bell syndrome) and from their families are reported. During the first postnatal years, protruding, large ears, full periorbital tissue, and thick septum and alae nasi were the most characteristic phenotypic findings, while after approximately 6 years of age a longish face with full lips and prominent maxilla and mandible became more distinct. It was estimated that a clinical suspicion of the fragile X syndrome could be made in most of the 16 boys from phenotypic findings in combination with the characteristic developmental profile described in our previous paper. The marker X chromosome was demonstrated in each of the 16 patients; the incidence of fra(X)-positive cells did not correlate with either age or the degree of mental retardation. 13 boys stemmed from 2 families, the other 3 were sporadic cases. In one family with 11 affected boys, the gene was transmitted by 4 brothers, grandfathers to the probands, who were intellectually normal; three of them did not show the clinical picture of the fragile X syndrome and did not express the marker. All mentally subnormal heterozygote females and one half of daughters of heterozygotes revealed the marker, but this was present only in a minority of non-retarded adult heterozygotes. In contrast to the overall incidence of about 1/4 to 1/3 mentally retarded heterozygotes, all 15 daughters of the four normal obligatory hemizygous brothers were of normal intelligence

Statistical characterization of the pubertal growth spurt

BACKGROUND This is a methodical investigation into the problem of estimating parameters for the pubertal spurt (PS). The variability involved in determining the timing, intensity and duration of the PS for height, leg height and biiliac width is estimated via a realistic simulation. Further, a decomposition of adolescent growth into a component due to the pubertal peak and one due to ongoing prepubertal velocity is evaluated. METHODS Data for 120 boys and 112 girls are available from 4 weeks to adulthood. The curve-fitting method is kernel estimation for distance, velocity and acceleration. RESULTS The age of peak velocity and the age of stopping of the PS are well determined. In contrast, the age of onset of the PS is less well determined. Intensity is less variable for the parameter peak velocity than for maximal acceleration. It is feasible to decompose adolescent growth into a component due to the pubertal peak and one due to ongoing prepubertal growth. CONCLUSIONS Nonparametric curve-fitting methods which do not rely on a parametric growth model can be successfully used to extract individual characteristics of the PS

Contribution of growth phases to adult size

Based on the data of the First Zurich Longitudinal Growth Study we investigate how interindividual differences in adult size arise in the variables leg height, sitting height and standing height, arm length, bi-iliac width and bihumeral width. Specifically, we are also interested in the question of whether across sexes and variables the same growth phases and the same parameters are predictive for achieving a certain adult size. A rather complex pattern emerges, demonstrating that regulation of growth is not the same for boys and girls and moreover is not the same for the six anthropometric variables studied. Prepubertal growth is characterized by its intensity (average velocity) and by its duration. Whereas duration has by itself no appreciable influence on adult size, prepubertal intensity determines adult size to a high degree across all variables and both sexes. The intensity of prepubertal growth determines adult size to a larger degree for boys than for girls. For a given size at the end of the prepubertal period, a small duration enhances the chance of obtaining a large adult size. Compared with prepubertal growth, the amount of variance of adult size explained is small for pubertal parameters, and--with respect to linear measures--significant for girls only. A small duration of prepubertal growth is in the following mainly compensated by a stronger pubertal spurt (PS), to a varying degree across variables. The overall picture which emerges indicates that sitting height--and to a lesser extent bihumeral width--develop in a more irregular fashion than the variables bi-iliac width and leg height

Growth processes leading to a large or small adult size

BACKGROUND The way in which a large size in anthropometric variables is achieved is a longstanding problem, since the pubertal spurt shows statistically and clinically little association with adult size (mostly studied for height). By analysing longitudinal growth of groups of subjects with a large or a small adult size separately for height, leg and sitting height, and bihumeral and biiliac width, we studied this problem in some detail. Of interest are growth patterns specific for these variables and for boys or girls. METHODS The data consist of 120 boys and 112 girls followed longitudinally from 4 weeks until adulthood. Statistically, structural average velocity curves were computed for each variable and each subgroup separately for comparison. This velocity curve represents the average intensity and the average tempo of growth. Since the area under the velocity curve is adult size, differences in the growth process can be visualized. RESULTS Both sexes show similar patterns in reaching a small or large adult size. The different variables, however, show marked differences. Only for legs is the pubertal spurt delayed for the large groups (with additional gains in prepubertal years). For sitting height and biiliac width, a slightly elevated velocity all along development (after 2 years) leads to a larger size and for bihumeral width the size of the pubertal peak is decisive. CONCLUSIONS The steering of growth to a certain target size is qualitatively similar for boys and girls, but quite different for different anthropometric variables. This leads to questions about endocrinological control for various parts of the body and differential bone growth in development

Growth of early and late maturers

BACKGROUND This is a study on the growth of subgroups of normal children, maturing early or late, in the variables height, leg and sitting height, arm length, biiliac and bihumeral width. While a longer growth period affects adult height only marginally, less is known about the other variables. It is also of interest to see in what way a shorter growth period is compensated by a higher velocity. METHODS Out of 120 boys and 112 girls followed from 4 weeks until adulthood, subgroups of 40 boys and 37 girls were formed with respect to the average timing (across variables) of the pubertal spurt as an indicator of maturity. RESULTS Only leg height shows a smaller adult size for early maturers. The shorter growth period is compensated by a higher prepubertal velocity and a higher level in pubertal years. The pubertal peak is a little larger for early maturing boys but not for girls. CONCLUSIONS There is an inherent pacemaker for growth that leads to the same adult size for a shorter growth period via a higher basic intensity. Legs are an exception since late maturers have, on average, longer legs as adults

Phenotypic heterogeneity of growth and psychometric intelligence in Prader-Willi syndrome: Variable expression of a contiguous gene syndrome or parent-child resemblance?

Phenotypic variability in children with Prader-Willi syndrome (PWS) was investigated with respect to variable expression of the contiguous gene syndrome and trait variance. In a prospective study, parent/child resemblance of anthropometric and psychometric measures was analyzed in 22 children with PWS (11 females and 11 males; 18 deletions, 4 uniparental disomy (UPD)) and in a control group (88 females and 88 males). The average child-midparent Z-score difference for height in females was –1.9 and in males –0.9, head circumference –1.7 and –1.0, and body mass index (BMI) 2.3 and 2.7, respectively. Intellectual performance of females and males was, on average, –2.7 and –2.6 below maternal performance. Range and standard deviation were moderately increased for height and head circumference, doubled for BMI, and unchanged for IQ. Parent/child correlations for anthropometric and psychometric measurements in the study group did not significantly differ from those of the control group. Exceptions were higher correlations between mothers and daughters for height (P < 0.05) and BMI (P < 0.01), and lower correlations for head circumference between midparent values and daughters (P < 0.05) than in the control group. In conclusion, parent–child resemblance in growth and intellectual development among children with PWS was found to be comparable to that noted in the normal population, indicating a strong determination by trait variance. Children with PWS differed significantly with respect to a lower trait level and—with the exception of IQ—a larger variability. The latter may indicate a variable expression of the contiguous gene syndrome

Sleep duration from ages 1 to 10 years: variability and stability in comparison with growth

OBJECTIVE: Our goal was to describe the variability of sleep duration (time in bed per 24 hours) in healthy children from 1 to 10 years of age in comparison with growth measures. METHODS: A total of 305 children were followed with structured sleep-related interviews and measurements of height and weight 12, 18, and 24 months after birth and then at annual intervals until 10 years of age. SD scores were calculated, and smooth curves were fitted by smoothing splines through the SD scores. The long-term variability channel within children (units SD score) was defined as the difference between the maximum and the minimum of the smooth curves and the short-term variability channel (units SD score) as the difference of the largest and the smallest deviations of the original SD scores from the smooth curve. RESULTS: Sleep duration remained within a long-term variability channel <0.5 SD score in 21% of the children (34% for height, 21% for weight). Nearly every second child (46%) stayed within a long-term variability channel <1.0 SD score (76% for height, 64% for weight). Sleep duration of approximately 90% of all children ran within a long-term variability channel of <2.0 SD score (corresponding, eg, to the range between the 2nd and the 50th percentile). No single child's sleep duration remained within a short-term variability channel <0.5 SD score, indicating fluctuations from year to year (60% for height, 53% for weight). An association between aspects of sleep duration and somatic growth was not observed at any age. CONCLUSIONS: Sleep duration during early and middle childhood shows large variability among children, as well as trait-like long-term stability and state-like yearly fluctuations within children. An individual approach to the child's sleep behavior is needed; expectations in terms of appropriate sleep duration of the child should be adjusted to the individual sleep need

The Importance of Childhood for Adult Health and Development—Study Protocol of the Zurich Longitudinal Studies

Evidence is accumulating that individual and environmental factors in childhood and adolescence should be considered when investigating adult health and aging-related processes. The data required for this is gathered by comprehensive long-term longitudinal studies. This article describes the protocol of the Zurich Longitudinal Studies (ZLS), a set of three comprehensive cohort studies on child growth, health, and development that are currently expanding into adulthood. Between 1954 and 1961, 445 healthy infants were enrolled in the first ZLS cohort. Their physical, motor, cognitive, and social development and their environment were assessed comprehensively across childhood, adolescence, and into young adulthood. In the 1970s, two further cohorts were added to the ZLS and assessed with largely matched study protocols: Between 1974 and 1979, the second ZLS cohort included 265 infants (103 term-born and 162 preterm infants), and between 1970 and 2002, the third ZLS cohort included 327 children of participants of the first ZLS cohort. Since 2019, the participants of the three ZLS cohorts have been traced and invited to participate in a first wave of assessments in adulthood to investigate their current health and development. This article describes the ZLS study protocol and discusses opportunities, methodological and conceptual challenges, and limitations arising from a long-term longitudinal cohort recruited from a study about development in early life. In the future, the ZLS will provide data to investigate childhood antecedents of adult health outcomes and, ultimately, will help respond to the frequent call of scientists to shift the focus of aging research into the first decades of life and, thus, to take a lifespan perspective on aging