Prepubertal girls with Turner syndrome and children with isolated SHOX deficiency have similar bone geometry at the radius.

CONTEXT: The low bone mineral density (BMD) and alterations in bone geometry observed in patients with Turner syndrome (TS) are likely caused by hypergonadotropic hypogonadism and/or by haploinsufficiency of the SHOX gene. OBJECTIVE: Our objective was to compare BMD, bone geometry, and strength at the radius between prepubertal girls with TS and children with isolated SHOX deficiency (SHOX-D) to test the hypothesis that the TS radial bone phenotype may be caused by SHOX-D. DESIGN AND SETTING: This comparative cross-sectional study was performed between March 2008 and May 2011 in 5 large centers for pediatric endocrinology. PATIENTS: Twenty-two girls with TS (mean age 10.3 years) and 10 children with SHOX-D (mean age 10.3 years) were assessed using peripheral quantitative computed tomography of the forearm. MAIN OUTCOMES: BMD, bone geometry, and strength at 4% and 65% sites of the radius were evaluated. RESULTS: Trabecular BMD was normal in TS (mean Z-score = -0.2 ± 1.1, P = .5) as well as SHOX-D patients (mean Z-score = 0.5 ± 1.5, P = .3). At the proximal radius, we observed increased total bone area (Z-scores = 0.9 ± 1.5, P = .013, and 1.5 ± 1.4, P = .001, for TS and SHOX-D patients, respectively) and thin cortex (Z-scores = -0.7 ± 1.2, P = 0.013, and -2.0 ± 1.2, P < .001, respectively) in both groups. Bone strength index was normal in TS as well as SHOX-D patients (Z-scores = 0.3 ± 1.0, P = .2, and 0.1 ± 1.3, P = .8, respectively). CONCLUSIONS: The similar bone geometry changes of the radius in TS and SHOX-D patients support the hypothesis that loss of 1 copy of SHOX is responsible for the radial bone phenotype associated with TS.

Defect-diaphragmatic ratio: a new parameter for assessment of defect size in neonates with congenital diaphragmatic hernia.

AIM: The aim of our study is to introduce a new objective method of perioperative evaluation of the size of diaphragmatic defect to enable comparison of results among various centres and methods used for diaphragmatic reconstruction. MATERIALS AND METHODS: Prospective observational study of neonates with congenital diaphragmatic hernia (CDH) and respiratory distress within 24 h of birth operated on from January 2009 to December 2011. Weight, length, thoracic shape and the diameters of diaphragmatic defect were measured. To determine the relative size of the defect, a defect-diaphragmatic ratio (DDR = defect area:diaphragm area × 100) was calculated. The measured and calculated data were subsequently compared between Gore-Tex patch group (GT) and primary repair group (PR). Mann-Whitney U test was used for statistical analysis. RESULTS: Forty-seven patients with CDH were admitted during study period. The overall survival rate was 79 % (37/47). Preoperative stabilization was achieved in 85 % (40/47). Survival of operated neonates was 93 % (37/40). Diaphragmatic reconstruction with Gore-Tex patch was used in 7 neonates (17 %), and primary repair in 33 (83 %). Mortality in Gore-Tex group was 29 %; mortality in primary repair group was 3 %. Data of anthropometric measurement were complete in 34 children (5 GT and 29 PR). Significant differences were found between GT group and PR group in the size of diaphragmatic defect with the transverse and sagittal diameters of defect (48.0 ± 5.7 vs. 30.1 ± 5.9, P < 0.00061; 34.0 ± 12.5 vs. 16.0 ± 7.3, P < 0.0022) and DDR (18.29 ± 4.60 vs. 5.77 ± 3.28, P < 0.0005), respectively. CONCLUSION: The value of DDR as an objective criterion of the extent of diaphragmatic defect was confirmed by the close correlation between DDR and feasibility of primary repair in the study group. This objective assessment of defect size may improve comparing various surgical techniques and results of different centres, and thus facilitates sharing experience with management of neonates with CDH.

Large diaphragmatic defect: are skeletal deformities preventable?

PURPOSE: The aim of study was to compare growth, nutritional status and incidence of chest wall deformities and scoliosis in survivors of large congenital diaphragmatic hernia (CDH) defect (Gore-Tex patch reconstruction) with survivors with smaller defects and primary reconstruction. MATERIALS AND METHODS: An anthropometric study of 53 children who underwent CDH repair in neonatal period was carried out. Weight, height, and skin-fold thickness were measured, scoliosis and chest wall deformity were evaluated. Body mass index (BMI) and thoracic index (TI) were calculated using standard rules. The measured data were compared with national population standard with the use of standard deviation score (SDS). According to the type of diaphragmatic reconstruction, the patients were divided into two groups [Gore-Tex patch (10) versus primary repair (43)]. Student t test and Fisher exact tests were used for statistical analysis. RESULTS: Pectus excavatum was found in 25 (47%) patients, poor posture in 33% and significant scoliosis in 5%. Compared with the population norm, CDH children had a significantly lower body height SDS (mean -0.39, p < 0.05), weight SDS (mean -0.75, p < 0.001), BMI (mean SDS -0.68, p < 0.001) and lower TI (mean SDS -0.62, p < 0.01). Gore-Tex versus primary repair group significantly differed in incidence of pectus excavatum and BMI (PE: p = 0.027, BMI SDS: p = 0.016). A majority of anthropometric parameters (weight, height, thoracic index, and thorax circumference) and incidence of scoliosis and poor posture in children after Gore-Tex patch reconstruction did not significantly differ from children after primary repair. CONCLUSION: The differences in some anthropometric parameters (weight, BMI, and TI) and in the skeletal deformity suggest that the CDH not only disturbs normal lung growth, but also seems to have implications on some other aspects of somatic development. Whether these changes could be related to the type of diaphragmatic reconstruction or rather to the size of the defect remains uncertain.

[Birth defects, medical outcome and somatic development in children conceived after intracytoplasmic sperm injection (ICSI)]. / Vrozené vývojové vady, zdravotní stav a somatický vývoj detí narozených po intracytoplazmatické injekci spermie.

OBJECTIVE: To analyze the incidence of birth defects, medical outcome and somatic development in children conceived after intracytoplasmic sperm injection (ICSI). DESIGN: Prospective open cross-sectional clinical study. SETTING: University hospital and private IVF unit. METHODS: 135 Czech children (59 girls, 76 boys) from singleton and twin pregnancies conceived after ICSI (age 03-9.5 years; median 5.9) were assessed during the period 2004-2006. The incidence of birth defects, medical outcome and somatic development were evaluated and compared with data of general population and/or with control group matched for sex and age. RESULTS: Birth defects were found in 133% of ICSI children (compared to 4.6% in children after spontaneous conception; p<0.001). The general health of ICSI children did not differ significantly compared to general population. ICSI children required more surgery or hospitalization compared to general population data. There is high rate (69.6%) among ICSI children in the care of various specialised clinics. Body height and weight in ICSI children is in normal range and corresponds to their growth potential. Head circumference in ICSI children is larger compared to reference data (0.43 SD; p<0.001). CONCLUSIONS: No clinically important differences in somatic development between ICSI and general population of Czech children were found. Birth defects were more frequent in ICSI children. The overall general health in ICSI children seems satisfactory but ICSI children were more likely to need health care compared to general population.

Association of tumour necrosis factor alpha variants with the CF pulmonary phenotype.

BACKGROUND: The pulmonary phenotype in patients with cystic fibrosis (CF), even in those with the same CF transmembrane conductance regulator (CFTR) genotype, is variable and must therefore be influenced by secondary genetic factors as well as environmental factors. Possible candidate genes that modulate the CF lung phenotype may include proinflammatory cytokines. One such protein is tumour necrosis factor alpha (TNFalpha), a member of the immune system. METHODS: Three polymorphic loci in the promoter (-851c/t, -308g/a, -238g/a) and one polymorphic locus in intron 1 (+691g ins/del) of the TNFalpha gene were typed by a single nucleotide primer extension assay in CF patients and healthy controls. Spirometric data and first age of infection with Pseudomonas aeruginosa were collected retrospectively from patients' medical records. RESULTS: An association was found between the TNFalpha +691g ins/del polymorphic locus and severity of CF lung disease. Patients heterozygous for +691g ins and +691g del were more likely to have better pulmonary function (mean (SD) forced expiratory volume in 1 second (FEV1) 79.7 (12.8)% predicted) than patients homozygous for +691g ins (mean (SD) FEV1 67.5 (23.0)% predicted; p = 0.008, mean difference 12.2%, 95% CI 3.5 to 21.0). Also, patients heterozygous for +691g ins and +691g del were more likely to have an older first age of infection with P aeruginosa (mean (SD) 11.4 (6.0) years) than patients homozygous for +691g ins (mean (SD) 8.3 (4.6) years; p = 0.018, mean difference 3.1 years, 95% CI 0.5 to 5.6). An association was also found with the -851c/t polymorphic locus. In the group of patients with more severe FEV1% predicted, a higher proportion of patients were homozygous for the -851c allele than in the other group of patients (p = 0.04, likelihood ratio chi2, odds ratio = 2.4). CONCLUSION: TNFalpha polymorphisms are associated with the severity of CF lung disease in Czech and Belgian patients with CF.

Czech dysplasia metatarsal type.

We report three further patients of the recently described new bone dysplasia-dominantly inherited pseudorheumatoid arthritis. The patients of this report have a similar clinical history, the same distinctive phenotype and almost identical radiographic findings. The only major difference is absence of weather dependent articular pain which characterized the family of the previous study. This report expands the clinical data of this bone dysplasia. All patients are Caucasians and originate from different parts of the Czech Republic. It seems that this disorder is quite a common constitutional bone disorder in this country. We propose the name of Czech Dysplasia Metatarsal Type for this unique disease.

Insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in cystic fibrosis: a positive effect of antibiotic therapy and hyperalimentation.

UNLABELLED: Patients with cystic fibrosis (CF) are underweight and growth retarded. This study tested the link between serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) levels and body height, nutritional status, pulmonary function tests and activity of inflammation in 92 subjects with CF (age 2.1-18.8 y). It also analysed the effect of short-term antibiotic treatment and hyperalimentation on IGF-I and IGFBP-3 levels in 33 subjects (age 3.6-33.7y) on 41 occasions. Both IGF-I (-1.19 +/- 0.17 SD) and IGFBP-3 levels (-0.66 +/- 0.12 SD; both p < 0.0001 vs 0) were decreased in cross-sectional measurements. Their standardized values were inversely proportional to age (IGF-I: r = -0.23, p = 0.03; IGFBP-3: r = -0.29, p = 0.005) and positively correlated with SDS of height (IGF-I: r = 0.40, p < 0.0001; IGFBP-3: r = 0.36, p = 0.0005) and of mid-arm circumference (IGF-I: r = 0.39, p = 0.0001; IGFBP-3: r = 0.38, p = 0.0002), and with pulmonary function tests. After a short-term course of intensive antibiotic therapy and hyperalimentation, IGF-I normalized (from -0.66 +/- 0.20 to 0.00 +/- 0.25 SD; p < 0.0001) and IGFBP-3 increased (from -0.78 +/- 0.15 to -0.53 +/- 0.16 SD; p = 0.002). IGFBP-3 correlated inversely with erythrocyte sedimentation rate (r = -0.40, p = 0.01). CONCLUSION: The levels of IGF-I and IGFBP-3 are markedly decreased in patients with CF and tend to normalise after a short course of antibiotic treatment and hyperalimentation.

Characterization of a novel 21-kb deletion, CFTRdele2,3(21 kb), in the CFTR gene: a cystic fibrosis mutation of Slavic origin common in Central and East Europe.

We report a large genomic deletion of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, viz., a deletion that is frequently observed in Central and Eastern Europe. The mutation, termed CFTRdele2,3(21 kb), deletes 21,080 bp spanning introns 1-3 of the CFTR gene. Transcript analyses have revealed that this deletion results in the loss of exons 2 and 3 in epithelial CFTR mRNA, thereby producing a premature termination signal within exon 4. In order to develop a simple polymerase chain reaction assay for this allele, we defined the end-points of the deletion at the DNA sequence level. We next screened for this mutation in a representative set of European and European-derived populations. Some 197 CF patients, including seven homozygotes, bearing this mutation have been identified during the course of our study. Clinical evaluation of CFTRdele2,3(21 kb) homozygotes and a comparison of compound heterozygotes for deltaF508/CFTRdele2,3(21 kb) with pairwise-matched deltaF508 homozygotes indicate that this deletion represents a severe mutation associated with pancreatic insufficiency and early age at diagnosis. Current data show that the mutation is particularly common in Czech (6.4% of all CF chromosomes), Russian (5.2%), Belorussian (3.3%), Austrian (2.6%), German (1.5%), Polish (1.5%), Slovenian (1.5%), Ukrainian (1.2%), and Slovak patients (1.1%). It has also been found in Lithuania, Latvia, Macedonia and Greece and has sporadically been observed in Canada, USA, France, Spain, Turkey, and UK, but not in CF patients from Bulgaria, Croatia, Romania or Serbia. Haplotype analysis has identified the same extragenic CF-haplotype XV-2c/KM. 19 "A" and the same infrequent intragenic microsatellite haplotype 16-33-13 (IVS8CA-IVS 17bTA-IVS 17bCA) in all examined CFTRdele2,3(21 kb) chromosomes, suggesting a common origin for this deletion. We conclude that the 21-kb deletion is a frequent and severe CF mutation in populations of Eastern- and Western-Slavic descent.

[Effect of estrogens on final body height in girls with a constitutionally tall stature--risk or benefit?]. / Ovlivnení definitivní telesné výsky estrogeny u dívek s konstitucne vysokým vzrustem--rizika nebo prínos?

OBJECTIVE: Investigation of the effect of a long-term oestrogen treatment on the growth and development of children, elaboration of a theoretical model for remaining growth of girls on a long-term oestrogen therapy predicting reduction of the final height in girls with constitutionally tall stature, analysis of early and late side-effects of therapy. TYPE OF STUDY: Open clinical study. NAME AND PLACE OF DEPARTMENT: Endocrine out-patient clinic of the Second Paediatric Department and gynaecological out-patient clinic for children and adolescents of the Gynaecological-Obstetric Department, Second Medical School--Charles University and University Hospital Prague--Motol. METHOD: Elaboration of theoretical model for remaining growth of girls on a long-term oestrogen therapy was based on an analysis of the remaining growth of upper and lower body segment of healthy Czech girls. RESULTS: The extent of assumed reduction of the final height in girls with constitutionally tall stature treated with oestrogen declines with advancing age at the onset of treatment. The optimal age for the onset of treatment is between 10 and 11 years. CONCLUSION: Treatment can be recommended only in girls with growth prediction above 185 cm and serious psychological difficulties resulting from excessive height, always after careful analysis of the biological development and growth prediction. In every case it is necessary to evaluate the possible benefit of treatment in relation to potential risks. The greatest problem is according to the authors late onset and overrating of the therapeutic possibilities.

[Cystic fibrosis--a disease of adolescents and adults?]. / Cystická fibróza--nemoc dospívajících a dospelých?

BACKGROUND: Cystic fibrosis (CF) is no longer a childhood disease. Since the identification of the gene in 1989 research has made advances and changed views on the pathogenesis, diagnosis and treatment. The objective of the present work is to make doctors treating adult patients familiar with modern therapeutic methods and their value. METHODS AND RESULTS: In the CF Centre of the Faculty Hospital in Prague Motol 349 patients are followed up on a long-term basis, incl. 95 who died since 1985. Hundred and twenty six (36.1%) patients survived to the age of 18 years, of those 41 died and 85 patients live. Comparison of semilongitudinal data of a group of 83 patients born before 1975 whose treatment during childhood and puberty was inadequate and 196 patients born in 1976-90 treated by modern methods proved the great effect of treatment on the course and prognosis of the disease. The median age at death increased during from 12.2 years in 1985-90 to 18.8 years in 1991-1998 (p = 0.004). The nutritional status of adult patients is satisfactory in 40.4%, poor in 33.3% and marginal in 26.3%. A normal pulmonary function was recorded in 17.5%, 22.8% are severely affected, the majority of patients (59.7%) has values within 40 to 80% of normal levels. CONCLUSIONS: Modern intensive treatment improved the prognosis and quality of live in patients with CF. Critical deterioration of the clinical condition shifted to the threshold of adult age. It is therefore essential that doctors treating such patients should be familiar with this issue.

[Late sequelae of comprehensive antineoplastic therapy in children and adolescents with solid extracranial tumors. Effect on growth, pubertal development and gonadal function]. / Pozdní následky komplexní protinádorové lécby u detí a mladistvých s extrakraniálními solidními nádory. Vliv na rust, pubertální vývoj a funkci gonád.

BACKGROUND: Modern treatment of oncological diseases increases markedly the chance of long-term survival and permanent recovery. Due to frequently highly aggressive treatment it is however associated with the risk of late sequelae in the surviving patients. Comprehensive care of patients includes therefore not only control of the neoplastic disease but also efforts of maximal improvement of the quality of life of the patients. In young subjects, in view of their long-term perspective, this problem is particularly important. METHODS AND RESULTS: In 32 patients (25 boys and 7 girls) with extracranial solid tumours without primary endocrinological symptomatology (m. Hodgkin, neuroblastoma, ganglioneuroblastoma, nephroblastoma, Ewings sarcoma and others) a single examination was made assessing height, body weight, grade of sexual maturation according to Tanner, in boys testicular volume by means of a orchidometer and 20 other anthropometric dimensions. The mean age at the time of examination was 16.5 +/- 4.1 years, the mean age at the onset of treatment 6.1 +/- 4.8 years. The patients height, -0.4 +/- 0.9 SD, differs from the Czech national standard (p = 0.025). Impaired growth was recorded in 12.5% patients and had heterogenous causes. The authors proved a negative effect of radiotherapy on the growth of the spine, most markedly in children subjected to irradiation of the abdomen and chest and a highly significant reduction of the testicular volume in boys after cytostatic treatment of m. Hodgkin. CONCLUSIONS: The results are consistent with studies made abroad and indicate the necessity of comprehensive long-term follow-up of somatic growth and development of the gonads in oncological child patients.

[Growth in children with the exudative enteropathy syndrome due to a congenital heart defect--cor triatriatum dextrum]. / Rust u dítete se syndromem exsudativní enteropatie na podklade vrozené srdecní vady--cor triatriatum dextrum.

Retarded growth in a child can be the sign of serious chronic disease. The authors present an account of a six-year-old boy where growth retardation persisted at least from the age of three. During this period his height dropped from the zone between the 25th and 50th percentile into the zone between the 3rd and 10th percentile. From the clinical point of view a large abdomen, loose stools and hypocalcaemia with tetany were striking, as they were moreover refractory to vitamin D2, calcitriol and calcium administration by the oral route. The authors revealed severe hypoproteinaemia, a 150 times increased value of alpha-1-antitrypsin in faeces, and exudative enteropathy syndrome was diagnosed. The cause was venous congestion due to a rare heart disease--cor triatriatum dextrum. The septum in the right atrium was resected. Immediately after surgery the consistency and frequency of stool decreased. Calcaemia and plasma protein levels reached normal levels within two months. A growth spurt of 11 cm/year followed. Fifteen months after operation the patient's height reached almost the 50th percentile.

Longitudinal follow-up of children after surgical treatment of scaphocephaly.

78 patients underwent surgery for scaphocephaly at the mean age of 1.2 (0.2-14.7) years in Faculty Hospital Motol in Prague. All operated children ("free bone flap" technique) have been longitudinally followed-up by the same neurosurgeon and by the same anthropologist. Non-invasive direct cephalometry has been an inevitable part of diagnostics, surgical treatment indication, postoperative follow-up and evaluation of the outcome of the treatment. Better cosmetic results in children operated before one year of age (the change of index cephalicus 6.5 units) in comparison with those treated later (3.7 units) is demonstrated (p = 0.02).

[Differential diagnosis in children with small stature]. / Diferenciální diagnostika u detí s malým vzrustem.

BACKGROUND: Physiological growth is a sensitive long-term indicator of child health. Impaired growth of children may be the first manifestation of a serious chronic disease. In order to find a rational examination procedure, the authors analyzed retrospectively the diagnosis in children with impaired growth who were referred for examination to the university hospital. METHODS AND RESULTS: In the course of 5.5 years 190 children (boys/girls, 124/66) with short stature, age 2.5 to 16.5 years were examined. In 93 (68/25, 48.9%) the condition was classified as short-normal, i.e. short but healthy, incl. 25 (11/14, 13.2%) with familial short stature, in 26 (21/5, 13.7%) constitutional growth retardation (and retarded puberty) and in 42 (36/6, 22.1%) a combination of the two conditions. In 97 children (56/41, 51.1%) a pathological condition was found: in 14 girls (7.4%) Turner's syndrome, in 55 children (37/18, 29.0%) deficiency of growth hormone, incl. 11 as a results of a tumour or anomaly of the CNS, and in 28 children (19/9, 14.7%) another serious cause of a growth disorder. In three families the authors detected an autosomal dominant disorder in a parent-child pair, the parent not being aware of the disorder (renal tubular acidosis, vitamin D resistant rickets, hypochondroplasia). Based on analysis of these data the authors suggest a rational differential diagnostic procedure in children with short stature. CONCLUSIONS: The stepwise examination of children with short stature is based on the unequivocal differentiation of short-normal children and assessment of the cause of the growth disorder in the other affected children. The procedure is focused on a sparing, rapid and accurate diagnosis with subsequent early treatment of children with a serious pathological condition.

[Improvement in the prognosis for growth in a boy with central precocious puberty and growth hormone deficiency treated concurrently with growth hormone and D-Trp-6-LHRH gonadoliberin analog]. / Zlepsení rustové prognózy u chlapce s centrální predcasnou pubertou a deficitem rustového hormonu soubeznou lécbou rustovým hormonem a analogem gonadoliberinu D-Trp-6-LHRH.

A boy with organically conditioned central precocious puberty and growth hormone deficiency (congenital cyst in the area of the third ventricle) is treated concurrently with an analog of gonadoliberine D-Trp-6-LHRH (Triptorelin) and growth hormone. Treatment was started at the calendar age od 9.4 years and bone age of 10.8 years. At the end of the first year of treatment the progression of bone age within one calendar year declined from 1.9 to 1.4 and after 18 months of treatment to 1.3. The growth rate increased from the initial value of 7.9 cm/year to 12.1 cm/year after 12 months of treatment, and subsequently reached a stable level of 10.2 cm/year. The growth prognosis increased markedly from the initial value of 168 cm to 174 cm at the end of the first year; a further improvement to 176 cm was recorded after 18 months of treatment.

[The effect of increased production of androgens on the development of body build morphology. Case report of an androgen-active tumor in a monozygotic twin]. / Vliv nadprodukce androgenu na vývoj morfogramu telesné stavby. (Kasuistika androgenne aktivního tumoru u monozygotního dvojcete).

The authors present an account on monozygotic twins where in one girl an androgen-active adenoma of the adrenal cortex during early puberty led to the development of the Morphogram of Body Build (Case-report of throughout the period of investigation intact from the hormonal aspect. Four years after resection of the tumour endocrine and anthropometric characteristics of the two sisters were evaluated: the hormonal status of both is normal, the somatic differences are manifested by a different final height, biacromial width and chest circumference. The results are conceived as a precedent for evaluation of risks associated with administration of anabolic steroids in children.

[Prediction of body height and shortening of the lower part of the body in adults with achondroplasia]. / Predikce telesné výsky a zkrácení dolního segmentu tela v dospelosti u achondroplazie.

The authors present the method of predicting the body height of patients with achondroplasia in adulthood and the method of predicting shortening of the lower segment of the body as compared to the trunk. They evaluate a group of 12 patients with achondroplasia at the age from 3 to 17 years. They compare the growth curves of patients with normal Czechoslovak population and with a group of American patients suffering with achondroplasia. The application of growth curves of American patients with achondroplasia appears to be the most suitable and simple graphical method for the prediction of the body height of the Czechoslovak patients suffering from achondroplasia. The method of the prediction of dwarfism of the lower segment of the body has been developed for the purpose of the rational indication of the stepwise prolongation therapy by the compression-distraction method. Analogically it will be possible to verify the growth curves for some other bone dysplasiae presented in literature and predict dwarfism of the lower segment of the body in adulthood, e.g. in hypochondroplasia, metaphyseal chondrodysplasia of the type of Schmid, Turner syndromes, etc.