Pregnancy in women with cystic fibrosis: 14 case reports and literature review / Cystás fibrosisban szenvedo nok várandóssága: 14 eset ismertetése és irodalmi áttekintés

Összefoglaló. A cystás fibrosisban szenvedo betegek várható élettartama jelentosen megnott az utóbbi évtizedben, egyre több beteg képes saját gyermeket vállalni. Célunk a cystás fibrosisban szenvedo várandós nok perinatalis és anyai történéseinek felmérése saját eseteink és az irodalmi adatok alapján. 14, cystás fibrosisban szenvedo no 16 várandósságáról számolunk be. Rögzítettük a várandósok életkorát, testtömegét, testmagasságát, testtömegindexét, légzésfunkciós értékeit a graviditás kezdetén és végén. Az anyai átlagéletkor szüléskor 21,6 (18-25) év volt. Az anyák graviditásának kezdetén a testmagasság átlaga 162 (150-175) cm, a testtömeg átlaga 57,6 (42-72) kg, a testtömegindex átlaga 21,4 (19,1-23,2) kg/m2 volt. A graviditás végén a testtömeg átlaga 62 (39-76) kg, a testtömegindex átlaga 23,6 (21,3-24,1) kg/m2 volt. A graviditás alatti súlygyarapodás átlaga 8 (1,5-21,5) kg volt. A légzésfunkciós értékek a graviditás kezdetén 2 betegnél voltak beszukültek. A graviditás alatt még 2 beteg légzésfunkciós értékei csökkentek. A sikeres graviditások száma 13 volt. 1 anya kétszer szült. A koraszülések száma 1 volt. A várandósság átlagosan a 38. (34-40.) gestatiós hét után 7 esetben császármetszéssel, 6 esetben hüvelyi szüléssel fejezodött be. A vetélések száma 3 volt. Az Apgar-pontszám minden esetben normális volt. 13 gyermek közül 11-nél a verejtékteszt nem volt emelkedett. 2 gyermeknél magas verejtékértékek voltak, egyikük c.1521_1523delCTT-heterozigóta, a másiknál génmutációt nem tudtunk igazolni. A cystás fibrosisban szenvedo nok általában jól tolerálják a várandósságot az esetek többségében. A kórosan beszukült tüdofunkcióval, alacsony tápláltsági állapottal és cukorbetegséggel rendelkezo nok nagyobb valószínuséggel számíthatnak káros következményekre. Az újszülöttek prognózisa általában jó, de számítani kell a koraszülés és a kis súllyal születés gyakoribb elofordulására. Ideális esetben a várandósságot elozetes tanácsadás útján kell megtervezni, és speciális cystás fibrosis csoportnak kell a várandósok ellátását figyelemmel kísérni, ideértve a cystás fibrosis kezelésében jártas szülészeket is. Kisszámú saját adatunk retrospektív elemzése megerosíti az irodalmi adatok tanúságait. Orv Hetil. 2021; 162(28): 1129-1136. Summary. The life expectancy of patients with cystic fibrosis has increased significantly in the last decade, with more and more patients being able to have their own children. The aim of our study was to assess the perinatal and maternal outcome of pregnant women with cystic fibrosis based on our own cases and literature data. We report 16 pregnancies in 14 women with cystic fibrosis. We recorded the age, body weight, height, body mass index, and respiratory function values of pregnant women at the beginning and end of pregnancy. The mean maternal age at childbirth was 21.6 (18-25) years. At the beginning of maternal pregnancy, the mean height was 162 (150-175) cm, the mean body weight was 57.6 (42-72) kg, and the mean body mass index was 21.4 (19.1-23.2) kg/m2. At the end of pregnancy, the mean body weight was 62 (39-76) kg and the mean body mass index was 23.6 (21.3-24.1) kg/m2. The weight gain under pregnancy was mean 8 (1.5-21.5) kg. The respiratory function values at the onset of pregnancy were narrowed in 2 patients. During pregnancy, the respiratory function values of 2 more patients decreased. The number of successful gestations was 13. A mother gave birth twice. The number of premature births was one. The pregnancy after the mean 38. (34-40.) gestational week was completed in 7 cases by cesarean section and in 6 cases by vaginal delivery. The number of miscarriages was 3. The Apgar score was normal in all cases. In 11 of 13 children, the sweat test was not elevated. 2 children had high sweat values, one of them is heterozygous with c.1521_1523delCTT, the other could not prove a gene mutation. Women with cystic fibrosis generally tolerate pregnancy well, in most cases. Women with poor lung function, low nutritional status, and diabetes are more likely to expect adverse consequences. The outcome of the newborns is good in general, but a common occurrence of premature birth and low birth weight is to be expected. Ideally, pregnancy should be planned through prior counseling and the care of pregnant women should be monitored by a specialized cystic fibrosis team, including obstetricians experienced in the treatment of cystic fibrosis. A retrospective analysis of our own small-number data confirms the evidence from the literature data. Orv Hetil. 2021; 162(28): 1129-1136.

[Neuroendocrine mechanisms controlling the development in puberty. A literature overview]. / A pubertas fejlodését szabályozó neuroendokrin mechanizmusok. Irodalmi áttekintés.

Puberty is the stage of development in human life, when the hypothalamus-hypophysis-gonad axis is re-activated after quiescence. Humanity has long been concerned with the idea of exogenous and endogenous factors and mechanisms that influence the temporal course of puberty neuroendocrine events. Recent discoveries have helped to understand the functioning of the neuroendocrine system. It has been clarified that kisspeptin plays a key role in puberty and regulation of fertility. However, in the function of the gonadotropin-releasing hormone (GnRH) pulse secretion, besides kisspeptin, neurokinin B, dynorphin neurons other positive and negative signals are involved, guiding the release of hormones of hypophysis gonadotropin. The knowledge of these nerves further enhanced the understanding of GnRH pulsation modulation by endocrine, metabolic and environmental impacts. The authors point out the risk of endocrine disruptors in the physiological course of puberty. The aim of the review is to provide a comprehensive picture of the research results of the physiology of kisspeptin, as the manipulation of kisspeptin signaling has the potential for novel therapies in patients with pathologically low or high luteinizing hormone (LH) pulsatility. Orv Hetil. 2018; 159(29): 1175-1182.

Baseline Characteristics and Disease Phenotype in Inflammatory Bowel Disease.

OBJECTIVES: Predicting short-term relapses and long-term prognosis is of utmost importance in paediatric inflammatory bowel disease (IBD). Our aim was to investigate the short-term disease outcome and medication during the first year in a paediatric incident cohort from Hungary. In addition, association laboratory markers and disease activity indices with short-term disease outcome and medication were analysed. METHODS: From January 1, 2008 to December 31, 2010, demographic data and clinical characteristics of newly diagnosed paediatric patients with IBD < 18 years of age were prospectively recorded. RESULTS: A total of 420 patients were identified (Crohn disease [CD] 266 and ulcerative colitis [UC] 124). Initially, 48% (124/256) of the patients with CD had moderate-to-severe disease (Pediatric Crohn's Disease Activity Index [PCDAI] > 31), and this rate decreased to 2.1% at 1-year follow-up. Proportion of patients with UC with moderate-to-severe disease (Pediatric Ulcerative Colitis Activity Index > 35) at diagnosis declined from 57.5% (69/120) to 6.8% at 1-year follow-up. Terminal ileal involvement correlated with higher initial C-reactive protein (CRP) (P = 0.021) and initial PCDAI (P = 0.026). In UC, elevated CRP (P = 0.002) was associated with disease extension. CRP and PCDAI at diagnosis were associated with the need for immunomodulators at 1 year in children with CD. Initial CRP was also associated with the need for immunomodulators in patients with UC at 1-year follow-up. CONCLUSIONS: At diagnosis, half of the patients with IBD had moderate-to-severe disease, and this rate decreased to <10% after 1 year. Initial CRP and PCDAI were related to the need for aggressive therapy in CD.

Factors influencing quality of life and disease severity in Hungarian children and young adults with cystic fibrosis.

BACKGROUND: The aim of our study was to evaluate factors affecting cystic fibrosis (CF) patients' health-related quality of life (HRQoL) and to assess the level of agreement on HRQol between children and their parents. METHODS: Fifty-nine patients (mean age: 14.03 ± 4.81 years) from 5 Hungarian CF centres completed the survey. HRQoL was measured using The Cystic Fibrosis Questionnaire-Revised (CFQ-R). Parents were asked to fill out a questionnaire about their smoking habits, educational level and history of chronic illness. Disease severity was assessed using the physician-reported Shwachman-Kulczycki (SK) score system. Spirometry, Body Mass Index (BMI) percentile (pc), hospitalisation and Pseudomonas aeruginosa (PA) infection were examined as physiologic parameters of CF, and the impact of these factors on HRQoL was assessed. A multivariate regression analysis was performed to identify the most important factors affecting HRQoL. The level of significance was set to 0.05. RESULTS: Passive smoking and parental educational level and chronic diseases status did not have a significant impact on the patients' HRQoL (p > 0.05). Significantly lower SK scores and spirometry values were found in low BMI pc patients (p < 0.001), in hospitalised (p < 0.01) and in PA-infected patients (p < 0.01), than in the adequate-weight, non-hospitalised and PA culture-negative subgroup. Lower CFQ-R scores were detected in hospitalised patients than in non-hospitalised patients in their Physical functioning domain. PA-infected patients had HRQoL scores that were significantly worse in the Body image (p < 0.01) and Respiratory symptoms (p < 0.05) domains than the PA culture-negative patients. Patients with a low BMI pc (<25th BMI pc) had significantly lower scores in the Eating, Body image and Treatment burden domains, than the adequate-weight patients (>25th BMI pc) (p < 0.01). A strong child-parent agreement was found in the Physical functioning domain (r = 0.77, p < 0.01). CONCLUSIONS: Passive smoking, parental educational level and chronic diseases of parents do not affect the HRQoL of CF patients. In contrast, hospitalisation, PA infection and malnutrition have a significant and negative impact on patients' HRQoL and the clinical severity of the disease. Parents and children were consistent in their scoring of symptoms and behaviours that were observable.

Incidence, Paris classification, and follow-up in a nationwide incident cohort of pediatric patients with inflammatory bowel disease.

OBJECTIVES: The aim of the study was to evaluate the incidence, baseline disease characteristics, and disease location based on the Paris classification in pediatric inflammatory bowel disease (IBD) in the Hungarian nationwide inception cohort. In addition, 1-year follow-up with therapy was analyzed. METHODS: From January 1, 2007 to December 31, 2009, newly diagnosed pediatric patients with IBD were prospectively registered. Twenty-seven pediatric gastroenterology centers participated in the data collection ensuring the data from the whole country. Newly diagnosed patients with IBD younger than 18 years were reported. Disease location was classified according to the Paris classification. RESULTS: A total of 420 patients were identified. The incidence rate of pediatric IBD was 7.48/105 (95% confidence interval [CI] 6.34/105-8.83/105). The incidence for Crohn disease (CD) was 4.72/105 (95% CI 3.82-5.79), for ulcerative colitis (UC) 2.32/105 (95% CI 1.71-3.09), and for IBD-unclassified 0.45/105 (95% CI 0.22-0.84). Most common location in CD was L3 (58.7%); typical upper gastrointestinal abnormalities (ulcer, erosion and aphthous lesion) were observed in 29.9%. Extensive colitis in patients with UC (E4, proximal to hepatic flexure) was the most common disease phenotype (57%), whereas only 5% of children had proctitis. A total of 18.6% of patients had ever severe disease (S1). Frequency of azathioprine administration at diagnosis was 29.5% in patients with CD, and this rate increased to 54.6% (130/238) at 1-year follow-up. In UC, only 3.3% received azathioprine initially, and this rate elevated to 22.5% (25/111). Use of corticosteroid decreased from 50% to 15.3% in patients with UC. Rate of bowel resection in patients with CD during the first year of follow-up was 5%. CONCLUSIONS: The incidence of pediatric IBD in Hungary was among the higher range reported. This is the first large, nationwide incident cohort analyzed according to the Paris classification, which is a useful tool to determine the characteristic pediatric CD phenotype.

[Quality of life in Hungarian patients with cystic fibrosis]. / Cystás fibrosisban szenvedo betegek életminoségének felmérése Magyarországon.

INTRODUCTION: Cystic fibrosis is a progressive multisystemic disease which affects the quality of life of patients. AIM: The aim of the study was to evaluate quality of life in Hungarian patients with cystic fibrosis. METHODS: Validated Hungarian translation of The Cystic Fibrosis Questionnaire - Revised was used to measure quality of life. Clinical severity was determined on the basis of Shwachman-Kulczycki score. Lung function was measured using spirometry. RESULTS: 59 patients were included from five centres in Hungary. The relationships between 8-13 year-old children self-report and parent proxy report was 0.77 (p<0.001) in physical functioning, 0.07 (p<0.001) in emotional functioning, 0.51 (p<0.001) in eating, 0.21 (p<0.001) in treatment burden, 0.54 (p<0.001) in body image, 0.49 (p<0.001) in respiratory symptoms and 0.40 (p<0.001) in digestive symptoms domains. CONCLUSIONS: In contrast to physical domains weak correlations were observed between answers obtained from children and their parents in psychosocial domains. The perception of both patients and their parents should be assessed when measuring quality of life in paediatric patients with cystic fibrosis.

Low mannose-binding lectin (MBL) is associated with paediatric inflammatory bowel diseases and ileal involvement in patients with Crohn disease.

BACKGROUND: Mannose-binding lectin (MBL) is a pattern-recognition molecule of the innate immune system and may be involved in the pathogenesis of inflammatory bowel disease (IBD). Our aim was to assess the prevalence of MBL deficiency in a cohort of patients with paediatric-onset IBD and study whether it is associated with the clinical manifestations, serum antibody formation, or genetic factors. METHODS: This prospective study included 159 paediatric patients (mean age: 14.0 years) with IBD [107 patients with Crohn disease (CD) and 52 patients with ulcerative colitis (UC)]. Furthermore, 95 controls were investigated. Serum samples were determined for MBL by enzyme-linked immunosorbent assay (ELISA) and for serologic markers [autoantibodies against Saccharomyces cerevisiae (ASCA) and perinuclear components of neutrophils (pANCA)] by indirect immunofluorescent assay. NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The MBL serum concentration was significantly lower in IBD patients(both with CD and UC) compared to controls (IBD, p=0.007, CD, p=0.04, UC p=0.004). Prevalence of low MBL level (<500 ng/mL) was significantly higher in both CD and UC groups compared to controls (p=0.002 and p=0.006). Furthermore, low MBL level was associated with isolated ileal involvement (p=0.01) and MBL deficiency (<100 ng/mL) with male gender (p=0.004) in patients with CD. We failed to confirm any correlation between MBL deficiency and serum autoantibodies or NOD2/CARD15 variants. CONCLUSIONS: Our results suggest that low MBL associated with paediatric-onset IBD and ileal CD may be considered an additional marker of the IBD pathogenesis.

Pancreatic autoantibodies and autoantibodies against goblet cells in pediatric patients with inflammatory bowel disease.

BACKGROUND: Significance of pancreatic autoantibodies determined by using exocrine pancreas (PAB) and antibodies against recombinant pancreas antigen (rPAB), as well as the importance of autoantibodies against goblet cells (GAB), is not known in pediatric patients with inflammatory bowel disease (IBD). Our aim was to determine the complex analysis of PAB, rPAB, GAB, antibodies against Saccharomyces cerevisiae, and perinuclear components of neutrophils in pediatric patients with IBD. Moreover, association with NOD2/CARD15 and disease phenotype was determined. METHODS: A total of 152 pediatric patients (median age 13.9 years) with IBD (103 patients with Crohn disease [CD] and 49 patients with ulcerative colitis [UC]) and 104 controls were included. Serum autoantibodies were determined by indirect immunofluorescence assay. NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The presence of PAB and rPAB was significantly higher in CD (34% and 35.9%) and in UC (20.4% and 24.5%) compared with pediatric control cohort (0% and 0%, P<0.0001). In addition, GAB positivity was significantly increased in patients with UC in comparison with CD and controls, respectively (UC, 12.2%; CD, 1.9%; controls, 1.9%; P=0.02). Specificity of PAB and rPAB was 100%; however, sensitivity was low. The combination of PAB and/or antibodies against Saccharomyces cerevisiae/perinuclear components of neutrophils improved the sensitivity of serological markers in CD (87.4%) and in UC (79.6%); specificities were 89.3% and 93.2%, respectively. Pancreatic autoantibodies (PAB, rPAB) and GAB were not related to clinical presentation, medical therapy, or need for surgery in CD or in UC. CONCLUSIONS: Pancreatic autoantibodies and GAB were specific for IBD, but the sensitivity was limited as well because there was lack of correlation with clinical phenotype. Combinations of these antibodies have shown increased sensitivity; therefore, it may be recommended in the diagnostic procedure of IBD.

[Effect of treatment with gonadotropin releasing hormone analogues in girls with idiopathic central precocious puberty]. / Az idiopathiás centrális pubertas praecox gonadotropin releasing hormon analóg terápiájának hosszú távú hatása leányoknál.

UNLABELLED: It has been proven for more than two decades that gonadotropin releasing hormone analogue therapy is the only choice of treatment in patients with central precocious puberty. AIMS: The aim of the authors was to assess the effect of gonadotropin releasing hormone analogue treatment on final height, body mass index, bone mineral density and ovarian function in girls with idiopathic central precocious puberty. METHODS: Predicted adult height, target height and achieved height due to therapy was assessed in 15 girls with idiopathic precocious puberty treated with gonadotropin releasing hormone analogue. At the beginning of the treatment, the age of the girls was 7.0±0.8 years (mean±SD) and at the end of the treatment 12±0.8 years. The duration of gonadotropin-releasing hormone analogue treatment was 4.48±0.8 years. At the time of achieving final height, the age of the patients was 18.2±2.0 years and the height was 160.4±7.1 cm. When final height was reached, the authors evaluated bone mineral density Z-score values, levels of bone markers and the function of the hypothalamic-pituitary-gonadal axis. 15 healthy prepubertal girls, 15 pubertal girls and 15 girls who reached final height matched for chronological age were selected as control groups. RESULTS: The majority of the gonadotropin releasing hormone-treated girls reached or almost reached their expected height predicted on the basis of the heights of their parents, but the therapy resulted only in a modest beneficial effect on height gain. Despite the fact that the body weight of patients increased during the treatment, there was no significant difference in their body mass index when they reached their final height as compared to controls. As compared to controls, patients had a decreased bone mineral density at the time when they reached their final height (lumbar spine 2-4 Z score, -0.27±1.2 vs. 0.5±0.7 in controls; p = 0.0377), which could be explained by their overweight that already existed before treatment, lack of exercise and poor calcium uptake. Their menarche occurred 12±4.6 months after discontinuing the treatment. CONCLUSIONS: Gonadotropin releasing hormone analogue therapy exerts a modest beneficial effect on final height gain. There are no detrimental effects on body mass index, bone mineral density and ovarian function after treatment. Side-effects are of minor severity and they are tolerable.

Diagnostic yield of upper endoscopy in paediatric patients with Crohn's disease and ulcerative colitis. Subanalysis of the HUPIR registry.

BACKGROUND, AIMS: According to Porto Criteria upper gastrointestinal (UGI) endoscopy is recommended in patients with suspected inflammatory bowel disease (IBD). Nevertheless, previous studies revealed frequent involvement of UGI tract even in patients with ulcerative colitis (UC). The aim of the present study was to determine the diagnostic role of esophagogastroduodenoscopy (EGD) and assess the prevalence and different aspects of UGI involvement in children registered in the Hungarian Pediatric IBD Registry (HUPIR) from 1st of January 2007 to 31th of December 2009. METHODS: Twenty seven institutes provided prospective follow-up data about newly diagnosed IBD patients to HUPIR. The registry was based on detailed questionnaire (76 parameters) involving anamnestic data, laboratory findings, activity indexes, diagnostic procedures, endoscopic examinations (EGD and ileocolonoscopy), and histological data. Localization and phenotype of disease were based on the Montreal classification criteria. RESULTS: During the 3-year period 420 children were diagnosed with IBD, 265 (63%) of them had Crohn's disease (CD), 130 (31%) UC, and 25 (6%) IBD-unclassified (IBD-U). The mean age at diagnosis was 13.2 years (range: 1.2-18 years). EGD was performed in 237 patients (56%), in most cases in patients suffering from CD. Macroscopic lesions on EGD were noted in 64% of patients with CD and 40% of children with UC. Characteristic lesions for CD (ulcer, erosion, aphthous lesion, and granuloma) were noted in 31% of CD patients, however, EGD helped to establish the final diagnosis in 9% of CD patients (diagnostic yield, 9%). CONCLUSIONS: There was a high frequency of UGI involvement in children with CD and UC. One third of CD patients showed significant lesions at upper endoscopy and one patient out of ten had real diagnostic help from EGD.

[Mixed gonadal dysgenesis associated with an isodicentric Y chromosome]. / Izodicentrikus Y-kromoszómához társuló kevert gonáddiszgenezis.

Authors report a case of mixed gonadal dysgenesis with a karyotype containing an isodicentric Y chromosome in mosaic form, which was diagnosed in an infant. They emphasize the necessity of the special investigations of newborn with perineoscrotal hypospadia and bilateral or unilateral maldescent testes immediately after birth. The result of accurate evaluation provides correct sex assignment and the prevention of the neoplastic degeneration of a dysgenetic gonad.

The 8.1 ancestral MHC haplotype is associated with delayed onset of colonization in cystic fibrosis.

Major cause of death in patients with cystic fibrosis (CF) is colonization with Staphylococcus aureus and Pseudomonas aeruginosa. The wide phenotypic variation in CF patients suggests that genes other than the cystic fibrosis transmembrane conductance regulator (CFTR) gene modify the disease. The 8.1 ancestral haplotype (8.1AH) in main histocompatibility complex is associated with alterations of the immune response. To study the influence of carriage of 8.1AH on frequency and onset of colonization in CF patients, DNA samples of 72 CF patients (39 homozygous and 33 heterozygous for DeltaF508) were genotyped for member alleles of the 8.1AH: HLA-DQB1*0201, HLA-DRB1*0301, receptor for advanced glycation end products (AGER) -429C, HSP70-2 -1267G (HSP70-2G) and tumor necrosis factor-alpha (TNF-alpha) -308A (TNF2). Colonization was verified by regular clinical and bacteriological screening. Frequency of colonization was significantly (P = 0.012) lower in the 8.1AH carriers; age, gender and DeltaF508 genotype-adjusted odds ratio to be colonized of the carriers versus non-carriers was 0.112 (0.024-0.520). According to survival analysis, patients with 8.1AH had significantly (P < 0.0001) longer colonization-free period compared with non-carriers. Our novel observations demonstrate that the 8.1AH is associated with delayed onset of colonization in CF, presumably by influencing defense mechanisms against infections.

[Prevalence of celiac disease in Turner syndrome]. / Coeliakia prevalenciája Turner-szindrómában.

INTRODUCTION AND AIM: Percentage of coeliac disease among patients with Turner syndrome is given differently in a few publication. The aim of the study was to assess prevalence of celiac disease in Turner syndrome. PATIENTS AND METHODS: Serological screening of coeliac disease were performed in 63 patients with Turner syndrome during the last 11.5 years (since 1994). Serological investigations were repeated yearly since 2003 in all patients, and the results of screening of new patients were completed. Theirs first case of coeliac disease was announced in 2004 in Gyermekgyógyászat (Hun). Further positive serological results were found after publication of the first case. RESULTS: Positive results were found in seven of 63 patients (two EmA and five antitransglutaminase IgA positivity). Intestinal biopsy was applied in all 7 cases. Coeliac disease was revealed by histologic analysis in the five cases - 5/63 (7.9%). CONCLUSION: The prevalence of coeliac disease in Turner syndrome seems to be higher than in general population. This can play role in the insufficient effect of growth hormone therapy in the affected patients. The high prevalence indicates that the connection between these disorders can not be coincidental. Their cases and the available data from the publications indicate that screening of coeliac disease in patients with Turner syndrome should be performed and intestinal biopsy is recommended in positive cases.

Disruption of the PDGFB gene in a 1;22 translocation patient does not cause Costello syndrome.

We studied a female patient initially diagnosed with Costello syndrome who carries an apparently balanced translocation, t(1;22) (q24.3;q13.1). Molecular characterization of the translocation revealed a mosaic of two derivative chromosomes 1 in her peripheral blood lymphocytes, in one of which the coding region of the platelet-derived growth factor (PDGFB; chromosome 22q13.1) gene was disrupted. Both the initial translocation and the secondary intrachromosomal rearrangement appear to have occurred by nonhomologous (illegitimate) recombination. In 18 patients with Costello syndrome, mutation analysis of the genes belonging to the PDGF/R family, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, and PDGFRB, revealed no pathogenic mutations. Reevaluation of the clinical symptoms of the translocation patient challenges the diagnosis of Costello syndrome in this patient. In total RNA isolated from lymphocytes of the translocation patient, we identified four different fusion transcripts consisting of PDGFB exons and parts of chromosome 1q24.3. In two of the mRNAs, exon 6 of PDGFB, encoding the 41 C-terminal amino acid residues, was absent. Immunofluorescence analysis showed that the wild-type protein was dispersed and formed a network-like structure in the extracellular matrix, whereas the two aberrant PDGFB proteins were localized in aggregates. We speculate that the biological consequences of the mutant PDGFB allele contributed to the unique disease phenotype of the translocation patient.

[Optimizing estrogen treatment in Turner syndrome]. / Törekvéseink az ösztrogénterápia optimalizálására Turner-szindrómában.

INTRODUCTION AND AIM: Authors deducibled from retrospective analysis of patients data with Turner syndrome, who reached near adult height and from results of many multicentre study, that induction of puberty should be designed individually. They show, that estrogen therapy used in their earlier practice for growth promoting did not improve final height of patients. METHODS: The patients were assigned into three groups. The group 1. consisted of untreated patients, who had spontaneous puberty (n = 10). The group 2. consisted of patients, who received oxandrolone and estrogen (n = 18). The group 3. consisted of patients treated with growth hormone (n = 17). In those patients received growth hormone estrogen treatment was started at the age of 14.7 +/- 1.97 years. RESULTS: The final height or near adult height was 144.0 +/- 4.6 cm, 143.5 +/- 1.8 cm, and 154.2 +/- 7.0 cm in group 1, 2 and 3 respectively. The final height was not greater in the group 2. compared to that found in patients who developed spontaneous puberty (group 1.). CONCLUSION: The individual estrogen therapy in patients treated with growth hormone allows feminization, as well as the best adult height, without the occurrence of the more serious mental disturbances.