Skeletal development of non-institutionalized children with low Intelligence Quotients

Children of both sexes with mild mental retardation show delays in skeletal maturation and cortical bone growth, but boys in general are more affected than girls. Skeletal age for both sexes is below normal in the younger age groups, but approaches normality at adolescence. None of the measures of IQ is significantly correlated with any of the regional measures of skeletal age in the hand-wrist. The approach toward normality of skeletal development in this population at adolescence is reflected in their normal time of first appearance of the adductor sesamoid. Anomalies of the hand-wrist reflect irregularities in comparing normal and low-IQ children. Only brachymesophalangy V displays significantly higher frequencies in the low-IQ groups. Due to the cross-sectional nature of the study and the different methods of classifying anomalies, little can be said about the other comparisons. Growth in cortical bone reflects a consistent trend for both the humerus and second metacarpal. While measures of total diameter and total cross-sectional area do appear to be below normal standards, the measures of the marrow do not. This finding accounts for a decreased cortical bone thickness and cross-sectional area in the low-IQ sample. All measures of the humerus correlate significantly with two IQ scores in the boys and all three scores in the girls. Measures of the total metacarpal and marrow area show significant correlations with the three IQ scores among low-IQ boys, while only measures of total metacarpal area show significant correlations with verbal IQ in low-IQ girls. The degree of mental deficiency, then, is only irregularly associated with deficits of bone size for age.     

Childhood retardation resulting in reduction of adult body size due to lesser adolescent skeletal delay

The skeletal maturation of 7972 rural children from the six Central American nations, aged one month through 22 years, is evaluated. The results suggest that retardation in skeletal maturation during childhood is significantly greater than during adolescence, while growth in body size shows a progressive delay from infancy through adolescence. In other words, the apparent improvement in skeletal maturation during adolescence is not associated with an equivalent “catch-up” in body size. Similarly, prolongation of the period of growth does not fully compensate for the slow rate of growth. It is postulated that the small stature in Central America is related to the marked childhood retardation and to the fact that during adolescence, the timing of skeletal maturation is less affected than growth in size.     

Serum zinc and somatic growth in children with growth retardation

A possible role for zinc deficiency in some cases of growth retardation in southern France was investigated. Control values for zinc for 160 children (age=12.5±2.4 yr) are 0.85±0.22 mg/L (mean ±2 SD). Twenty-five children with low serum zinc values (<0.63 mg/L) and 25 matched short children with normal serum zinc values (>0.63 mg/L) were studied. Children in the two groups did not differ significantly in age, pubertal development, stature, and weight. For the 25 children whose serum values were low, we found significantly lower values for bone age delay, growth velocity in mm/month, as well as the ratio between calculated growth velocity and theoretical growth velocity for the bone age (so that zincemia was correlated to these parameters in the whole sample of 50 subjects). Nevertheless, no significant difference could be found between the two groups for serum somatomedin C, serum osteocalcin values, and GH responses to the GH stimulatory tests (exercise test, overnight sampling, insulin-induced hypoglycemia, arginine test). Therefore, low serum zinc is associated with a retardation in both somatic growth and pubertal maturation.     

Skeletal growth in school children: maturation and bone mass

Skeletal growth and development was evaluated in 322 white children (age 6 to 14) using three different methods: (1) ¹²⁵I photon absorptiometry, (2) compact bone measures on radiographs, and (3) Greulich-Pyle skeletal age from hand-wrist radiographs. Bone mineral content, measured by photon absorptiometry, increased at an incremental rate of about 8.5% each year. Skeletal age was a poor predictor of skeletal status, i.e., bone mineral content (14% error), and did not decrease the predictive error substantially more than did chronological age. Gross morphology (height and weight) was in fact a better predictor of bone mineral content than were skeletal age, chronological age, and radiographic morphometry. Skeletal age deviations were correlated with deviations in body size. A bone mineral index was devised which was independent of body size and this index was also independent of skeletal age. Skeletal age is imprecise (3 to 6 months error) and the range of variation in normal children (13 months) overlaps the maturational delay of the malnourished and diseased. The difficulties in using skeletal maturation are discussed and it is suggested that particular maturational indices be used which better indicate skeletal growth than does a composite skeletal age.     

Growth and bone maturation in children from two regions of the F.R.G. differing in the degree of air pollution: results of the 1974 and 1984 surveys

Growth and bone maturation criteria were used in this collaborative study to assess the potential health risk posed by excessive air pollutant emission. The study consisted of two surveys carried out 10 years apart. During this decade, a substantial emission reduction through the effective control efforts was achieved in the index area, but not so in the reference area where the situation remained virtually unchanged during this period. In terms of body height and height-weight proportionality, no significant differences were found between areas and years of investigation. In contrast, the bone age retardation encountered in the children from the polluted area was statistically significant, both at 1974 and 1984 surveys, despite the appreciable improvement in this developmental criterion for boys in 1984. This was true for both group mean values and the percentages of individuals exhibiting the bone maturation delay greater than 10 months.     

Growth assessment of children exposed to low frequency electromagnetic fields at the Abu Sultan area in Ismailia (Egypt)

A cross-sectional study was carried out to assess the growth of 780 children of both sexes, aged between 0-12 years, and living at two different areas in Ismailia, Egypt, with approximately similar socioeconomic standards. Based on a designed questionaire, the exposed group was formed of 390 children from the Abu Sultan area. They were chosen from families living within 50 meters nearby high voltage electric power lines. Another 390 children from the El-Sheikh Zayed area were chosen as the control group. Standard anthropometric measurements were carried out for each child. Plain X-ray was done on the hands of 200 randomly selected children from both groups (100 each) to assess their bone maturation. In the exposed group the weight was significantly decreased only at birth, while the circumferences of the head and chest as well as the height were significantly reduced at all studied ages. The radiological study revealed a significant delay in carpal bone ossification of the exposed children. In conclusion: Exposure to low frequency electromagnetic fields emerged from high voltage electric power lines increases the incidence of growth retardation of children. Isolating these power lines in a scientific way in order to shield both the magnetic and electric fields or removing them far away from the inhabitant areas is recommended.     

Bone maturation reflects the secular trend in growth

The aim of this study was to compare a series of X-rays from the mid-1990s with another taken in the mid-1980s in order to test the possibility that environmental causes affect the skeletal maturation. The first group of subjects included a total of 1,057 girls and 1, 055 boys participating in a project for Japan and China health research in 1986. The second group of subjects included a total of 382 girls and 629 boys participating in a project for bone mineral density research in 1996. The skeletal maturity score using the Tanner-Whitehouse 2-RUS method was used as the fundamental datum. This score was used to represent each group. The Wilcoxon's rank sum test was applied to examine the significance of the difference between the 1986 and the 1996 groups. The 1996 children had not matured more than the 1986 children; children in both groups reached the given scores at almost the same ages. In girls, there was little difference between the groups at 7 years of age, but it declined from 8 years of age onward. Some apparent differences arose at ages 14 and 15, but ceased by age 16 in girls. In boys, no differences were found in those aged from 7 to 17 years, except for 12-year-olds. We did not detect much of a difference in bone maturation between the 1986 and 1996 groups of children, and no differences in height during the same period. Our findings suggest that bone maturation reflects the secular trend in growth.     

Skeletal defects in paternal uniparental disomy for chromosome 14 are re-capitulated in the mouse model (paternal uniparental disomy 12)

Human paternal uniparental disomy for chromosome 14 (upd(14)pat) presents with skeletal abnormalities, joint contractures, dysmorphic facial features and developmental delay/mental retardation. Distal human chromosome 14 (HSA14) is homologous to distal mouse chromosome 12 (MMU12) and both regions have been shown to contain imprinted genes. In humans, consistent radiographic findings include a narrow, bell-shaped thorax with caudal bowing of the anterior ribs, cranial bowing of the posterior ribs and flaring of the iliac wings without shortening or dysplasia of the long bones. Mice with upd(12)pat have thin ribs with delayed ossification of the sternum, skull and feet. In both mice and humans, the axial skeleton is predominantly affected. We hypothesize that there is an imprinted gene or genes on HSA14/MMU12 that specifically affects rib/thorax development and the maturation of ossification centers in the sternum, feet and skull with little effect on long bone development.     

Carpal bone maturation assessment by image analysis from computed tomography scans

Bone maturation is the only reliable indicator of growth and its radiologic assessment with or without automated systems is a qualitative method. Image processing allows the study of bone maturation with quantitative data. Carpal bone maturation was studied in 20 children (13 boys and 7 girls, ages ranging from 4 to 15 years) without any clinical evidence of endocrine disease by image analysis from computed tomography (CT) scans. Each wrist CT scan was processed in order to extract the carpal bones and to measure quantitative data regarding volume, axes of inertia and density for each bone. The volumes and the length of the inertia axes were significantly correlated with age. Whatever the age, there were strong correlations between the volume or the length of the main inertia axis of one carpal bone and that of all others. The decrease in the carpal bone volume measured from the processing procedure compared with the theoretical volume of bone defined from the length of the three inertia axes indicated a change in bone shape during growth. Although the mean density was constant, there was an increase in the standard deviation of density with age. Skeletal maturity assessment with image analysis from CT scans seems to be a good complementary investigation to determine bone age in children.     

A Genotype-First Approach for the Molecular and Clinical Characterization of Uncommon De Novo Microdeletion of 20q13.33

Background

Subtelomeric deletions of the long arm of chromosome 20 are rare, with only 11 described in the literature. Clinical features of individuals with these microdeletions include severe limb malformations, skeletal abnormalities, growth retardation, developmental and speech delay, mental retardation, seizures and mild, non-specific dysmorphic features.

Methodology/Principal Findings

We characterized microdeletions at 20q13.33 in six individuals referred for genetic evaluation of developmental delay, mental retardation, and/or congenital anomalies. A comparison to previously reported cases of 20q13.33 microdeletion shows phenotypic overlap, with clinical features that include mental retardation, developmental delay, speech and language deficits, seizures, and behavior problems such as autistic spectrum disorder. There does not appear to be a clinically recognizable constellation of dysmorphic features among individuals with subtelomeric 20q microdeletions.

Conclusions/Significance

Based on genotype-phenotype correlation among individuals in this and previous studies, we discuss several possible candidate genes for specific clinical features, including ARFGAP1, CHRNA4 and KCNQ2 and neurodevelopmental deficits. Deletion of this region may play an important role in cognitive development.     

Mental Representation of Arm Motion Dynamics in Children and Adolescents

Motor imagery, i.e., a mental state during which an individual internally represents an action without any overt motor output, is a potential tool to investigate action representation during development. Here, we took advantage of the inertial anisotropy phenomenon to investigate whether children can generate accurate motor predictions for movements with varying dynamics. Children (9 and 11 years), adolescents (14 years) and young adults (21 years) carried-out actual and mental arm movements in two different directions in the horizontal plane: rightwards (low inertia) and leftwards (high inertia). We recorded and compared actual and mental movement times. We found that actual movement times were greater for leftward than rightward arm movements in all groups. For mental movements, differences between leftward versus rightward movements were observed in the adults and adolescents, but not among the children. Furthermore, significant differences between actual and mental times were found at 9 and 11 years of age in the leftward direction. The ratio R/L (rightward direction/leftward direction), which indicates temporal differences between low inertia and high inertia movements, was inferior to 1 at all ages, except for the mental movements at 9 years of age, indicating than actual and mental movements were shorter for the rightward than leftward direction. Interestingly, while the ratio R/L of actual movements was constant across ages, it gradually decreased with age for mental movements. The ratio A/M (actual movement/mental movement), which indicates temporal differences between actual and mental movements, was near to 1 in the adults'' groups, denoting accurate mental timing. In children and adolescents, an underestimation of mental movement times appeared for the leftward movements only. However, this overestimation gradually decreased with age. Our results showed a refinement in the motor imagery ability during development. Action representation reached maturation at adolescence, during which mental actions were tightly related to their actual production.     

Conditional expression of constitutively active estrogen receptor α in chondrocytes impairs longitudinal bone growth in mice

Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caERα(ColII), expressing constitutively active mutant estrogen receptor (ER) α in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caERα(ColII) mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caERα(ColII) mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caERα(ColII) mice. These results suggest that ERα is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.     

Environmental effects on skeletal versus dental development: Using a documented subadult skeletal sample to test a basic assumption in human osteological research

This study examines the relationship between measures of skeletal and dental development and socioeconomic factors in a 20th century documented skeletal sample of children from Portugal. The skeletons are of known sex and chronological age, and include other biographic data, such as cause of death. Growth in the length of the long bone is used as a measure of skeletal growth, and schedules of tooth formation are used as a measure of dental development. These two measures of physiological age were compared to chronological age, to assess growth and developmental status. Socioeconomic indicators were obtained from the supporting documentation, and include the occupation of the father and the place of residence, which were used to build a socioeconomic classification based on two groups, one of low and the other of high socioeconomic status. Growth and development status was then compared in these two groups. Results show that socioeconomic differences are much more pronounced in skeletal growth than in dental development. This largely supports the assertion that dental development is buffered against environmental factors relative to skeletal development. However, in this study, skeletal maturation could not be assessed, and findings indicate that dental development can show significant delays at the lower end of the socioeconomic gradient.     

Examination of the X chromosome by STS-PCR screening for the presence of submicroscopic deletions

Cytogenetically undetectable deletions are suspected to be an important cause of mental retardation and developmental delay, as suggested by the observation that about 7% of children with undiagnosed mental retardation have rearrangements affecting the chromosome ends. Screening the whole genome for regions of aneuploidy smaller than 5 Mb is not feasible, but the availability of a high resolution map of the X chromosome means that it is possible to look for deletions in males by PCR. We have screened 96 affected males and their 96 unaffected fathers with 110 markers distributed across the X chromosome. No deletions were found in either group. Our results show that the prevalence of deletions greater than 1 Mb in children with mental retardation is less than 3.9% (95% confidence interval). We conclude that X chromosome deletions in the size range 1–5 Mb are a rare cause of mental retardation in males. Received: 22 July 1998 / Accepted: 11 September 1998     

A comparison between methods of calculating skeletal age (Greulich-Pyle)

The skeletal age of each individual bone of the hand-wrist was assessed in serial radiographs of 169 Melbourne children. Seven different methods were used to obtain area skeletal ages from these bone skeletal ages. Methods employing arithmetic means of all the bone skeletal ages, excluding only extreme values, excluding those derived from the carpals or from other selected bones yielded similar means during the age range studied in each sex. There were large, but not significant, differences between the means derived from averages of the skeletal ages of the most and least mature bones and those derived from all the bone skeletal ages. A system of weighting and exclusion of bone skeletal ages led to the recording of area skeletal ages that differed from the others and fluctuated markedly for individuals until ossification had occurred in every carpal bone. The findings suggest that the exclusion of the skeletal ages of the carpal bones or the use of selected skeletal ages could lead to quicker assessments without real changes in means and variability.     

Intraskeletal variability in bone mass

For methodological or other reasons, a variety of skeletal elements are analyzed and subsequently used as a basis for describing general bone loss and mass. However, bone loss and mass may not be uniform within and among skeletal elements of the same individual because of biomechanical factors. We test the hypothesis that a homogeneity in bone mass exists among skeletal elements of the same individual. Measures indicative of bone mass were calculated from the midshafts of six skeletal elements from the same individuals (N = 41). The extent of intraskeletal variability in bone mass (relative cortical area) was then examined for the entire sample, according to age, sex, and pathological status. The results of the analysis showed that all measures reflect a heterogeneity in bone mass (P 相似文献   

Depression,smoking, physical inactivity and season independently associated with midnight salivary cortisol in type 1 diabetes

Background

Trisomy 9p is an uncommon anomaly characterised by mental retardation, head and facial abnormalities, congenital heart defects, kidney abnormalities, and skeletal malformations. Affected children may also show growth and puberty retardation with delayed bone age. Auxological and endocrinological data are lacking for this syndrome.

Methods

We describe three girls and one boy with 9p trisomy showing substantial growth failure, and we evaluate the main causes of their short stature.

Results

The target height was normal in all families, ranging from 0.1 and -1.2 standard deviation scores (SDS). The patients had a low birth-weight (from -1.2 to -2.4 SDS), birth length (from -1.1 to -3.2 SDS), and head circumference (from -0.5 to -1.6 SDS). All patients presented with substantial growth (height) retardation at the time of 9p trisomy diagnosis (from -3.0 to -3.8 SDS). The growth hormone stimulation test revealed a classic growth hormone (GH) deficiency (GHD) in patients 1, 3, and 4. In contrast, patient 2 was determined to have a GH neurosecretory dysfunction (GHNSD). The plasma concentrations of IGF-I and IGFBP-3 were low in all patients for their ages and sexes (from -2.0 to -3.4 SDS, and from -1.9 to -2.8 SDS, respectively). The auxological follow-up showed that those patients who underwent rhGH treatment exhibited a very good response to the GH therapy, whereas patients 3 and 4, whose families chose not to use rhGH treatment, did not experience any significant catch-up growth.

Conclusions

GH deficiency appears to be a possible feature of patients with 9p trisomy syndrome. These patients, particularly those with growth delays, should be evaluated for GH secretion.     

Tau syndrome (thrombocytopenia and absent ulnar) with mental retardation and facial dysmorphy.

A girl with pancytopenia (hemoglobin 9 g. 2,000 PMN. 75,000 platelets) was examined at 23 years of age. She had microcephaly, facial dysmorphy, skeletal deformities (kypho-scoliosis, club feet, club hands) and mental retardation. Puberty was normal, Roentgenograms showed bilateral agenesia of the distal part of the ulna with dislocation of the head of the radius. No other skeletal parts were absent. The condition is probably due to an autosomal recessive gene, the parents being second cousins.