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

Adipose-derived stem cells (ADSCs) and muscle precursor cells (MPCs) for the treatment of bladder voiding dysfunction

Purpose: Bladder outflow obstruction (BOO) is common in the elderly and can result in bladder voiding dysfunction (BVD) due to severe bladder muscle damage. The goal of this research was to evaluate the use of adult stem cells for the treatment of BVD due to decreased muscle contractility in a rat model. Materials and methods: Adipose-derived stem cells (ADSCs) and muscle precursor cells (MPCs) were harvested from male Lewis rats and expanded in culture. BOO was induced by tying a suture around the urethra. Six weeks after obstruction, the development of BVD was confirmed by cystometric analysis in conscious rats, histology and molecular investigations. Injection of ADSCs or MPCs into the bladder wall and synchronous deligation was performed 6weeks after the obstruction. After stem-cell treatment, morphological and functional changes were assessed. Age-matched rats and animals without cellular therapy but deligation-only served as controls. Results: Voiding pressures decreased progressively 6weeks after obstruction with increased bladder capacities. Structural changes of the detrusor muscle occurred during the time of obstruction with an increased connective tissue-to-smooth muscle ratio and decreased SMA/smoothelin expression. After stem-cell injection, improved voiding pressures and voiding volumes were observed together with recovered tissue architecture. RT-PCR and Western blotting showed an up-regulation of important contractile proteins. Conclusions: We established a reliable model for BVD and demonstrated that ADSCs and MPCs can prevent pathophysiological remodelling and provide regenerated bladder tissue and function

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

Short stature, myopia, severe developmental delay, and peculiar facial appearance in two brothers: A new syndrome?

We report on 2 brothers with short stature, microcephaly, myopia, retarded osseous maturation, severe developmental delay, and minor anomalies including temporal narrowing, periorbital fullness, full cheeks in infancy, and protruding lower lip. Both brothers and their parents had normal chromosomes. Fluorescence in situ hybridization with probes from all (sub-)telomeric chromosomal regions excluded a structural rearrangement involving telomeric segments. Because the pattern of congenital abnormalities is not like that of any well-known multiple congenital anomaly/mental retardation syndrome, we suggest a previously undescribed syndrome of autosomal recessive or X-linked inheritance

Natural history of twin disruption sequence

Intrauterine death of one fetus in a monochorionic twin pregnancy is associated with high morbidity and mortality in the surviving cotwin. Thromoboplastic material from the dead twin may pass to the circulation of the living twin via placental anastomoses and cause tissue necrosis by direct embolization or by activating intravascular coagulation. Alternatively, acute blood loss into the dying twin through placental anastomoses may result in hypotension and hypoxic-ischemic damage to cerebral and visceral tissue in the surviving twin. The resulting clinical picture is referred to as twin disruption sequence. Affected twins have rarely been followed beyond the neonatal period and the long-term development of such children is unknown. Here, we present a natural history and neurological assessment of 18 patients with twin disruption sequence, whom we have followed over several months to years. © 2004 Wiley-Liss, Inc