scholarly journals Origin of the X-chromosome influences the development and treatment outcomes of Turner syndrome

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12354
Author(s):  
Ying Zhang ◽  
Yongchen Yang ◽  
Pin Li ◽  
Sheng Guo
Keyword(s):  
Growth Factor ◽  
Treatment Outcomes ◽  
Turner Syndrome ◽  
Clinical Features ◽  
X Chromosome ◽  
Sexual Development ◽  
Bone Age ◽  
Age Difference ◽  
Gh Treatment ◽  
Mother’S Age

Turner syndrome (TS) affects 1/2,500 live-born female infants. In the present study, we attempted to clarify the relationship between genetic factors (especially the X-chromosome origin), clinical features, body/sexual development, and treatment outcomes. We enrolled 39 female infants aged between 3 and 14 years. General demographic and clinical features were documented, and laboratory analysis of blood samples was performed. Subject karyotype was determined by G-banding of 50 peripheral white blood cells, and the parenteral origin of the retained X-chromosome was determined. Next, growth hormone (GH) treatment was prescribed for 12 months, with follow-ups performed as determined. For patient groups separated according to X-chromosome origin, the basal height, bone age, insulin-like growth factor (IGF)-1, and insulin-like growth factor binding protein-3 (IGFBP-3) levels were comparable; however, after the 12-month treatment, significant differences in the height increase and IGF-1 levels were observed. If the X-chromosome (or chromosomes) originated from both parents, the increase in height was less substantial, with lower serum IGF-1 levels. The uterine size, prolactin level, increased weight after treatment, and bone age difference after treatment negatively correlated with the mother’s age at the time of birth. The mother’s height at the time of birth demonstrated a negative correlation with the basal bone age difference and a positive correlation with the IGF-1 level. In summary, the retained X-chromosome derived from both parents is associated with poorer response to GH therapy. The mother’s age and height at the time of birth can strongly impact the patient’s body/sexual development and the response to GH treatment. Thus, the mother’s age and height at the time of birth and the parental origin of the X-chromosome should be carefully considered before developing a treatment plan for TS.

scholarly journals The Effects of Growth Hormone Treatment on Bone Mineral Density and Body Composition in Girls with Turner Syndrome

2006 ◽  
Vol 91 (11) ◽  
pp. 4302-4305 ◽  
Author(s):  
Mim Ari ◽  
Vladimir K. Bakalov ◽  
Suvimol Hill ◽  
Carolyn A. Bondy
Keyword(s):  
Bone Mineral Density ◽  
Body Composition ◽  
Turner Syndrome ◽  
Lean Body Mass ◽  
Body Mass ◽  
Bone Mineral ◽  
Bone Age ◽  
Treated Group ◽  
Mineral Density ◽  
Gh Treatment

Abstract Background: Many girls with Turner syndrome (TS) are treated with GH to increase adult height. In addition to promoting longitudinal bone growth, GH has effects on bone and body composition. Objective: The objective was to determine how GH treatment affects bone mineral density (BMD) and body composition in girls with TS. Method: In a cross-sectional study, we compared measures of body composition and BMD by dual energy x-ray absorptiometry, and phalangeal cortical thickness by hand radiography in 28 girls with TS who had never received GH and 39 girls who were treated with GH for at least 1 yr. All girls were participants in a National Institutes of Health (NIH) Clinical Research Center (CRC) protocol between 2001 and 2006. Results: The two groups were similar in age (12.3 yr, sd 2.9), bone age (11.5 yr, sd 2.6), and weight (42.8 kg, sd 16.6); but the GH-treated group was taller (134 vs. 137 cm, P = 0.001). The average duration of GH treatment was 4.2 (sd 3.2) yr (range 1–14 yr). After adjustment for size and bone age, there were no significant differences in BMD at L1–L4, 1/3 radius or cortical bone thickness measured at the second metacarpal. However, lean body mass percent was higher (P < 0.001), whereas body fat percent was lower (P < 0.001) in the GH-treated group. These effects were independent of estrogen exposure and were still apparent in girls that had finished GH treatment at least 1 yr previously. Conclusions: Although GH treatment has little effect on cortical or trabecular BMD in girls with TS, it is associated with increased lean body mass and reduced adiposity.

scholarly journals Adult height after GH therapy in 188 Ullrich-Turner syndrome patients: results of the German IGLU Follow-up Study 2001

2002 ◽  
pp. 625-633 ◽  
Author(s):  
MB Ranke ◽  
CJ Partsch ◽  
A Lindberg ◽  
HG Dorr ◽  
M Bettendorf ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
Adult Height ◽  
Bone Age ◽  
First Year ◽  
Gh Therapy ◽  
Gh Treatment ◽  
Height Gain ◽  
Puberty Onset

OBJECTIVES: We aimed to evaluate the factors influencing true adult height (HT) after long-term (from 1987 to 2000) GH treatment in Ullrich-Turner syndrome (UTS) based on modalities conceived in the 1980s. DESIGN: Out of 347 near-adult (>16 Years) patients from 96 German centres, whose longitudinal growth was documented within KIGS (Pharmacia International Growth Database), 188 (45, X=59%; bone age >15 Years) were available for further anthropometric measurements. RESULTS: At a median GH dose of 0.88 (10th/90th percentiles: 0.47/1.06) IU/kg per week, a gain of 6.0 (-1.3/+13) cm above the projected adult height was recorded. Variables were recorded at GH start, after 1 Year GH, puberty onset, and last visit on GH therapy. At these visits, the median ages were 11.7, 12.7, 14.2, 16.6 and 18.7 Years; and median heights, 0.4, 1.1, 1.7, 1.7 and 1.3 SDS (UTS) respectively. Height gain (DeltaHT) after GH discontinuation was 1.5 cm. Total DeltaHT correlated (P<0.001) negatively with bone age and HT SDS at GH start, but positively with DeltaHT after the first Year, DeltaHT at puberty onset, and GH duration. Final HT correlated (P<0.001) positively with HT at GH start, first-Year DeltaHT, and HT at puberty onset. Body mass index increased slightly (P<0.05), with values at start and adult follow-up correlating highly (R=0.70, P<0.001). No major side effects of GH occurred. CONCLUSIONS: GH dosages conceived in the 1980s are safe but too low for most UTS patients. HT gain and height are determined by age and HT at GH start. Height gain during the first Year on GH is indicative of overall height gain. After spontaneous or induced puberty, little gain in height occurs.

scholarly journals X-chromosome gene dosage as a determinant of impaired pre and postnatal growth and adult height in Turner syndrome

2016 ◽  
Vol 174 (3) ◽  
pp. 281-288 ◽  
Author(s):  
Elodie Fiot ◽  
Delphine Zenaty ◽  
Priscilla Boizeau ◽  
Jeremy Haigneré ◽  
Sophie Dos Santos ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
X Chromosome ◽  
Multiple Testing ◽  
Adult Height ◽  
Gene Dosage ◽  
Postnatal Growth ◽  
Target Height ◽  
Anthropometric Parameters ◽  
Gh Treatment ◽  
Chromosome Gene

ObjectiveShort stature is a key aspect of the phenotype of patients with Turner syndrome (TS). SHOX haploinsufficiency is responsible for about two-thirds of the height deficit. The aim was to investigate the effect of X-chromosome gene dosage on anthropometric parameters at birth, spontaneous height, and adult height (AH) after growth hormone (GH) treatment.DesignWe conducted a national observational multicenter study.MethodsBirth parameter SDS for gestational age, height, and AH before and after GH treatment respectively, and height deficit with respect to target height (SDS) were classified by karyotype subgroup in a cohort of 1501 patients with TS: 45,X (36%), isoXq (19%), 45,X/46,XX (15%), XrX (7%), presence of Y (6%), or other karyotypes (17%).ResultsBirth weight, length (P<0.0001), and head circumference (P<0.001), height and height deficit with respect to target height (SDS) before GH treatment, at a median age of 8.8 (5.3–11.8) years and after adjustment for age and correction for multiple testing (P<0.0001), and AH deficit with respect to target height at a median age of 19.3 (18.0–21.8) years and with additional adjustment for dose and duration of GH treatment (P=0.006), were significantly associated with karyotype subgroup. Growth retardation tended to be more severe in patients with XrX, isoXq, and, to a lesser extent, 45,X karyotypes than in patients with 45,X/46,XX karyotypes or a Y chromosome.ConclusionThese data suggest that haploinsufficiency for an unknown Xp gene increases the risk of fetal and postnatal growth deficit and short AH with respect to target height after GH therapy.

scholarly journals Cytogenetic and genomic analysis of a patient with turner syndrome and t(2;12): a case report

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Paola E. Leone ◽  
Verónica Yumiceba ◽  
Ariana Jijón-Vergara ◽  
Andy Pérez-Villa ◽  
Isaac Armendáriz-Castillo ◽  
...  
Keyword(s):  
Case Report ◽  
Turner Syndrome ◽  
Clinical Features ◽  
X Chromosome ◽  
Genetic Disorder ◽  
Genomic Analysis ◽  
Common Finding ◽  
Mild Intellectual Disability ◽  
First Case ◽  
Conventional Cytogenetics

Abstract Background Turner syndrome is a genetic disorder that affects women. It is caused by an absent or incomplete X chromosome, which can be presented in mosaicism or not. There are 12 cases of Turner syndrome patients who present structural alterations in autosomal chromosomes. Case presentation The present case report describes a patient with a reciprocal, maternally inherited translocation between chromosomes 2 and 12 with a mosaicism of X monosomy 45,X,t(2;12)(p13;q24)[95]/46,XX,t(2;12)(p13;q24)[5]. Through genetic mapping arrays, altered genes in the patient were determined within the 23 chromosome pairs. These genes were associated with the patient’s clinical features using a bioinformatics tool. Conclusion To our knowledge, this is the first case in which a translocation (2;12) is reported in a patient with Turner syndrome and confirmed by conventional cytogenetics, FISH and molecular genetics. Clinical features of our patient are closely related with the loss of one X chromosome, however mild intellectual disability can be likely explained by autosomal genes. The presence of familial translocations was a common finding, thus emphasizing the need for familiar testing for further genetic counselling.

scholarly journals Combination of Gonadal Dysgenesis and Monosomy X with a Novo Translocation (13,14)

2018 ◽  
Vol 2018 ◽  
pp. 1-3 ◽  
Author(s):  
Hanane Latrech ◽  
Houssein Madar ◽  
Ahmed Gaouzi
Keyword(s):  
Turner Syndrome ◽  
Clinical Features ◽  
X Chromosome ◽  
Gonadal Dysgenesis ◽  
Clinical Presentation ◽  
Sex Chromosome ◽  
De Novo ◽  
First Case ◽  
Chromosome Disorder ◽  
De Novo Translocation

Turner syndrome is a common sex chromosome disorder characterized by complete or partial absence of an X chromosome. The spectrum of its clinical features and cytogenetics are various. We report new chromosomal formula revealed by DSD and associated with translocation (13,14). To our knowledge, this is the first case of 45X, t(13;14) de novo translocation as a variation of Turner syndrome in a patient with this clinical presentation.

Parental Origin of the X-Chromosome Does Not Influence Growth Hormone Treatment Effect in Turner Syndrome

2012 ◽  
Vol 97 (7) ◽  
pp. E1241-E1248 ◽  
Author(s):  
Marie Devernay ◽  
Diana Bolca ◽  
Lamia Kerdjana ◽  
Azzedine Aboura ◽  
Bénédicte Gérard ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
X Chromosome ◽  
Treatment Effect ◽  
Hormone Treatment ◽  
Population Based ◽  
First Year ◽  
Parental Origin ◽  
Gh Treatment ◽  
Height Gain ◽  
Previously Treated

Abstract Context: The parental origin of the intact X-chromosome has been reported to affect phenotype and response to GH treatment in Turner syndrome (TS). Objective: Our objective was to evaluate the influence of the parental origin of the X-chromosome on body growth and GH treatment effect in TS. Design and Setting: We conducted a population-based cohort study of TS patients previously treated with GH. Participants: Participants included patients with a nonmosaic 45,X karyotype; 556 women were identified as eligible, 233 (49%) of whom participated, together with their mothers. Data were analyzed for 180 of these patients. Main Outcome Measures: We performed fluorescence in situ hybridization analysis to exclude mosaicism and microsatellite analysis of nine polymorphic markers in DNA from the patients and their mothers. The influence on growth and effect of GH were analyzed by univariate and multivariate methods. Results: The X-chromosome was of paternal origin (Xpat) in 52 (29%) of 180 and of maternal origin (Xmat) in 128 (71%) of 180 patients. Height gain from the start of GH treatment to adult height was similar in Xmat and Xpat patients (+2.1 ± 0.9 vs. +2.2 ± 0.8 TS sd score, P = 0.45). The lack of influence of parental origin of the X-chromosome was confirmed in multivariate analysis. Parental origin of the X-chromosome also had no effect on the other growth characteristics studied, including growth velocity during the first year on GH treatment. Patient height was correlated with the heights of both parents and was not influenced by the parental origin of the X-chromosome. Conclusion: In this, the largest such study carried out to date, the parental origin of the X-chromosome did not alter the effect of GH treatment or affect any other features of growth in TS.

scholarly journals SAT-107 Improved Adult Height in Brazilian Turner Syndrome Patients Treated with Growth Hormone

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Renata Da Cunha Scalco ◽  
Adriana Farrant Braz ◽  
Alexsandra C Malaquias ◽  
Sonir Roberto Rauber Antonini ◽  
Gil Guerra-Junior ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Turner Syndrome ◽  
Adult Height ◽  
Delayed Diagnosis ◽  
Bone Age ◽  
Treated Group ◽  
Gh Treatment ◽  
Significant Difference ◽  
Referral Hospitals ◽  
Height Gain

Abstract Background: Short stature is the most frequent clinical manifestation in Turner syndrome (TS), occurring in 98% of these patients. Growth hormone was shown to improve adult height in TS patients from diverse genetic backgrounds. However, there are few studies on adult height in TS patients from developing countries, where the diagnosis is frequently delayed. Objective: To compare adult height between GH-treated and untreated TS patients. Patients and methods: 120 GH-treated and 109 GH-untreated TS patients from 3 referral hospitals in Brazil were evaluated. The most common reasons for not treating TS patients with GH were late diagnosis or GH unavailability. Data on karyotype, parents’ height, puberty development and GH treatment were obtained from their medical records. Adult height was determined when growth velocity was inferior to 1cm/year during a minimum follow-up period of 12 months. Results: The frequency of 45,X karyotype was similar between the groups (48.7% vs. 41.9% in GH-treated vs. GH-untreated TS patients, respectively, P= 0.639). GH-treated TS patients started GH therapy at a chronological age (CA) of 11.2 ± 3.7 yr, bone age of 9.3 ± 3.1 yr, height SDS (British 1965 standards) -3.1 ± 1.1. GH mean dose was 48µg/kg.d and GH treatment duration was 5.4 ± 3.0 yr. Estrogen replacement was started late, at CA of 14.3 ± 2.0 yr in GH-treated and at 14.9 ± 1.9 yr in GH-untreated patients, and the rate of spontaneous puberty was similar between the groups (GH-treated 16.8% vs. GH-untreated 22,8%, P=0.304). Adult height was significantly higher after GH treatment (150.1 ± 5.8 cm vs. 143.3 ± 7.2 cm in GH-treated vs. untreated TS patients, respectively, P &lt; 0.001), even with a small but significant difference in target height between the groups (158.2 ± 4.8 vs. 159.8± 4.5 cm in GH-treated vs. untreated TS patients, respectively, P= 0.015). More than half of the TS GH-treated patients reached normal adult height (equal or higher than 150.2 cm), whereas only 15.6% of GH-untreated patients reached it. Conclusion: Despite the delayed diagnosis of TS patients in our cohort, GH treatment was associated with a significant height gain, and the TS GH-treated group was around 7 cm taller than the GH-untreated group.

Sign in / Sign up

Export Citation Format

Share Document