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The meiotic or mitotic origin of most cases of Turner syndrome remains unknown, due to the difficulty in detecting hidden mosaicisms and to the lack of meiotic segregation studies. We have had the opportunity to study one pair of monozygotic twins concordant for Turner syndrome of paternal origin. The paternal origin of the single X chromosome was determined by polymerase chain reaction (PCR) amplification. No mosaicism was detected for the X or Y chromosome. In this case, a meiotic error during gametogenesis would be a likely origin of X monosomy. To determine if meiotic errors are more frequent in the father of these monozygotic twins concordant for Turner syndrome of paternal origin, molecular studies in spermatozoa were conducted to analyse sex chromosome numerical abnormalities. A total of 12520 sperm nuclei from the twins' father and 85338 sperm nuclei from eight normal donors were analysed using three-colour fluorescent in-situ hybridization. There were significant differences between the twins' father and control donors for XY disomy (0.22 versus 0.11%, P < 0.001) and total sex chromosome disomy (0.38 versus 0.21%, P < 0.001). These results could indicate an increased tendency to meiotic sex chromosome non-disjunction in the father of the Turner twins. [ABSTRACT FROM PUBLISHER]

Background and Objective: Many countries have developed screening programs for CH that bring about a normal somatic and psychological development. The aim of this study is to evaluate the evolution of cases detected by the screening program of congenital hypothyroidism in Catalonia., Patients and Methods: The was a descriptive, longitudinal study of a series of 136 cases of congenital hypothyroidism detected by the screening program in Catalonia from 1986 to 1997 and who had been checked in the Maternal-infantile Vall d'Hebron Hospital in Barcelona. Follow-up was carried out for growth and a psychological exploration was performed (McCarthy test and WISC-R)., Results: Males (30 cases, 22.1%) and females (106 cases, 77.9%) with congenital hypothyroidism of this study had a height, weight and BMI that were not different from those of the current population of Barcelona. Height was 0.5 SD above the Tanner reference values of 1966 and BMI was one SD above the Roland-Cachera reference values of 1982. This secular acceleration of growth has been observed in all developed countries. In a sample of 37.5% of the cases, psychological development did not differ from that of the reference population. However, a greater intensity of neonatal hypothyroidism and its most delayed normalization correlated negatively with the score in the psychological tests., Conclusions: Once normalization of growth and psychological development are achieved, the screening program of congenital hypothyroidism in Catalonia should be optimized by initiating treatment as soon as possible to avoid the possibility that some children do not reach their complete intellectual potential., (Copyright 2009 Elsevier España, S.L. All rights reserved.)

Aims and Methods: Postnatal growth was evaluated in a cross-sectional study of 486 Spanish children, 241 girls and 245 boys, born small for gestational age (SGA), without height catch-up growth between the ages of 2 and 8 years [height <-2SD of age- and sex-matched controls born appropriate for gestational age (AGA)]. SGA was defined as birth weight and/or length values <-2SD of those of the born AGA control population. Weight and height values were grouped in 0.5+/-0.15-year intervals from birth to adult height and compared with those of age- and sex-matched controls born AGA. A total of 1,985 height measurements were recorded in girls and 2,113 in boys. Adult or near-adult height was reached in 50 girls and 42 boys. Mean, SD and mean Z-score values at each age interval were calculated. Dysmorphic syndromes and chronic illnesses were excluded., Results: Mean height Z-score values ranged from -5.56 to -3.12 during the first two years of life and remained between -5.25 and -2.42 thereafter until adult height, and mean weight Z-score values ranged from -3.66 to -2.26 from birth to two years of age and remained between -3.05 and -0.94 thereafter until adult height. Mean Z-score values of near-adult or adult height were -2.83 in girls (n=50) and -2.74 in boys (n=42). Midparental adult height corrected for sex was -1.45 +/- 0.5 in girls (n=150) and -1.60 +/-0.6 in boys (n=185). Height +2SD values of SGA children were similar to -2SD values of age- and sex-matched AGA controls (non statistically significant)., Conclusions: Our data show that short children born SGA are shorter than children born AGA from the age of two years onwards and that their adult height is below that of their corresponding midparental height by more than 1 SD.

Context: We studied two sisters with congenital hypothyroidism and choreoathetosis but not respiratory distress., Objective: The aim of this study was to establish the genetic defect that causes this phenotype and study the molecular mechanisms of the pathology by means of functional analysis., Design: Sequencing of DNA, expression vectors generation, EMSAs, transfections experiments as well as bioinformatics analysis were performed., Results: We found a new single deletion (825delC) in one allele of the TITF1/NKX2.1 gene. The mutation located in the C-terminal domain generates a nonsense thyroid transcription factor 1 (TTF1) protein, with 22 amino less and rich in positive charges. This protein shows diminished binding to DNA, does not interfere with wild-type (wt) TTF1 binding, and fails to activate reporter genes harboring the thyroglobulin (Tg), thyroperoxidase (TPO), or surfactant protein B (SP-B) promoters. In addition, the mutant (mut) protein has a dominant-negative effect on the transcriptional activity of wt TTF1 in a promoter-specific manner, inhibiting the transcription of Tg and TPO but not of SP-B. Using a Gal4 reporter system, we demonstrate that the mut protein is not transcriptionally active and does not likely compete with the wild type for coactivators. Interestingly, the mut protein impairs the wt capacity to synergize with paired box 8 (PAX8). This cooperation is necessary for Tg and TPO transcription but dispensable for SP-B expression., Conclusion: These results are concordant with the phenotype of the two sisters studied and demonstrate a differential role for TTF1 in the different tissues in which it is expressed.

Gestational age and neonatal anthropometric parameters are currently used to evaluate fetal growth and are predictive factors of perinatal and postnatal morbidity and mortality. We performed a retrospective analysis of neonatal anthropometric parameters (weight, vertex-heel length and head circumference) in 1,470 live preterm neonates born between 1997 and 2002 and a prospective analysis of the same parameters in 1,786 live newborns of both sexes born in 2001 and 2002, products of single 37-42 week uncomplicated pregnancies in healthy Spanish Caucasian mothers. A progressive increase in these parameters with gestational age and sexual dimorphism were observed from the 30th week of gestational age onwards, with statistically-significant differences (p<0.05) at 38-42 weeks of gestational age. An increase in weight and length values in relation to previous Spanish studies was also documented in preterm newborns. It is estimated that 10-15% of children born small for gestational age (SGA) do not experience catch-up growth by the age of 3 years and may have short stature in adulthood. Preliminary data of a cross-sectional study on spontaneous growth in boys and girls born SGA without postnatal catch-up growth show that their +2 SD values of height are similar to -2 SD values of our normal control population of children born with adequate weight and length for gestational age (AGE). However, weight +2 SD values are similar to mean values of control children born AGE. In summary, our data show sexual dimorphism in neonatal anthropometric growth parameters and that these parameters change with time and may be updated. In addition children born SGA without postnatal catch-up are shorter and have higher weight than age-, height- and sex-matched controls born AGE.

Background: Reduced fetal growth is a potential risk factor for development of metabolic abnormalities in later life. The relationship between low birthweight and impaired glucose tolerance, type 2 diabetes and insulin resistance in adulthood has been well documented., Purpose: Assuming that fetal undernutrition is associated with insulin resistance in middle age, we elected to study whether this process may already be present in young adults and adolescents born small for gestational age (SGA)., Subjects and Methods: Children born in Vall d'Hebron Hospital Infantil, Barcelona, between 1986 and 1989 and between 1978 and 1983 with birthweights below the third centile for the local standard values, were invited to participate in the present study. Of those, 51 (22 girls and 29 boys) were pre-pubertal with 9.4 +/- 0.2 years of age and 49 (29 girls and 20 boys ) were post-pubertal, with 17.3 +/- 0.3 years of age. All patients underwent a standard, 2-hour oral glucose tolerance test. Insulin and glucose responses were compared with our previously published data in control children with normal birthweight., Results: The insulin response at 30 min after glucose load was significantly higher (p < 0.001) in pre- and post-pubertal girls and boys formerly SGA than in controls. In addition, the girls also had a higher insulin response at 60 and 120 min. Mean serum insulin (MSI), the area under the insulin curve during the glucose challenge, was statistically increased in pre- and post-pubertal boys and girls born SGA when compared to controls., Conclusion: The presence of high insulin levels after an oral glucose challenge in children and adolescents born SGA might be considered as an early marker of subsequent insulin resistance in adulthood. Furthermore, our population offers the opportunity to study the natural course of hyperinsulinemia and its outcome. Follow-up of this cohort may be helpful in distinguishing a subset of young children and adolescents in whom therapeutic intervention could be done., (Copyright 2002 S. Karger AG, Basel)

Background: Intrauterine growth retardation (IUGR) is considered to be responsible for approximately 20% of short stature in adulthood. Although GH secretion is normal in the majority of cases, excellent results have been published by some authors using GH to treat children with height deficiency due to IUGR., Patients and Methods: Thirty children with a history of IUGR with chronological ages between 2 and 7 years and height less than 2 SD were randomized in two groups for one year: a) control group, no treatment, 14 cases, and b) treatment group, 1 U/kg/week of recombinant GH, 16 cases. Growth and maturation were analysed periodically in both groups. In addition, serum levels of GH, IGF-I, IGFBP3 and GHBP were measured before and under treatment and adverse events were assessed in treatment group., Results: In the treated group significant increments in growth rate, cm/year (median = 6.91 vs 9.94), improvement in height SDS (median = -2.19 vs -1.63) and positivation of growth rate (median = -0.13 vs 3.17) were observed compared with the control group. Bone age evolved parallelly to chronological age and the height age/bone age ratio increased throughout the study under GH therapy. Hormonal findings in the treated group showed a significant increase in IGF-I and IGFBP3 values. Glycaemia levels increased without exceeding upper normal levels in the treated group., Conclusion: GH was effective in promoting growth in this short-term study in children with height deficiency due to IUGR. Close follow-up is required to detect any adverse event, particularly those related to carbohydrate metabolism.

In this study, we report an accurate method to determine the parental origin of sex chromosome aneuploidies or polyploidies and to detect low percentage mosaicisms. We have amplified by polymerase chain reaction (PCR) five polymorphic markers along the X chromosome (DXS1283E, DYS II, DMD49, AR and DXS52) and three markers along the Y chromosome (SRY, DYZ3 and DYZ1). False-negative results were discarded by the simultaneous amplification of Y markers and of internal controls. We have applied this protocol to a series of 14 Turner syndrome patients with a 45,X karyotype. We have detected sex chromosome mosaicisms in two patients. The parental origin of the syndrome has been determined in the other 12 patients.

A fetal goiter was detected by ultrasonography in a woman receiving potassium iodide. After this medication was discontinued at 29 weeks, a fetal hypothyroidism was confirmed by cordocentesis, and two doses of levothyroxine were administered by amniocentesis. At 34 weeks repeated cordocentesis showed fetal euthyroidism and ultrasonography shrinkage of the goiter. Growth and development normal at 1 year.

Objective: To evaluate bone mineral density (BMD) in prepubertal and in adolescent and young adult patients with the salt-wasting form of congenital adrenal hyperplasia (CAH)., Design: A relationship between bone mineral content and risk for osteoporotic fractures has been observed in adulthood. Infancy, childhood, and adolescence are critical periods for skeletal mineralization; thus, chronic diseases may impair bone mass peaking, particularly if children and adolescents are overexposed to glucocorticoids, as may occur in patients with CAH. Lumbar L2-L4 BMD values were measured by dual x-ray absorptiometry and compared with those of 471 age- and sex-matched controls., Patients: Thirty-three patients with the salt-wasting form of CAH were studied. Sixteen (10 girls and 6 boys; age range, 1.5 to 8.3 years) were prepubertal and 17 (13 women and 4 men; age range, 17.1 to 28.2 years) were adolescent and young adults who had reached final height and had presented normal pubertal development and normal gonadal function thereafter. The average doses of hydrocortisone (mg/m body surface/day) received from diagnosis in the neonatal period to BMD evaluation were 21.2 +/- 2.2 and 22.3 +/- 2.6, respectively., Results: Mean BMD Z score values were 0.16 +/- 1.01 in prepubertal patients and 0.06 +/- 1.02 in adolescent and young adult patients with no statistically significant differences with age- and sex-matched controls. Mean height Z score values were -0.03 +/- 1.13 in prepubertal patients and -1.13 +/- 0.62 in adolescent and young adult patients with significant differences between the latter and their respective age- and sex-matched controls., Conclusion: Long-term glucocorticoid therapy does not impair bone mass peaking in CAH patients with normal gonadal function, even though their adult height values are low.

Background: The height growth pattern in 24 patients with the salt-wasting from of congenital adrenal hyperplasia was retrospectively evaluated from the neonatal period to attainment of adult height., Patients and Methods: All patients were on mineralcorticoid therapy and received hydrocortisone (mg/m2 body surface and day. Mean +/- SD): 34.53 +/- 8.2 during the first year of life, 22.83 +/- 4.1 from then to the puberty onset and 21.83 +/- 3.6 during puberty. Height was measured every 3-4 months and compared with that of the normal age- and sex-matched controls., Results: Height differences with respect to reference population (M +/- SD) were: +0.38 +/- 0.82 in the neonatal period; -2.21 +/- 1.1 at one year of age; -0.76 +/- 1.25 at three years of age; -0.45 +/- 0.99 at the onset of puberty and -1.34 +/- 0.79 at attainment of adult height. Adult height differed significantly (p < 0.01) from control values and in girls from those of their mothers (p < 0.05). Hyperandrogenism, evaluated through urinary 17-ketosteroids, testosterone, delta 4 androstenedione and DA-S, was not documented during prepuberty and puberty., Conclusions: Our patients showed a lower growth rate than those of the control population during the two periods of higher growth potentiality: the first year of life and puberty, and this results in adult height impairment.