Talking about Height and Quality of Life: A Content-Analysis of Focus Group Discussions with Short-Statured Children and Their Parents in the US

Background: To understand what life is like for US children with a diagnosis of Growth Hormone Deficiency or Idiopathic Short Stature, the impact of short stature on Health related Quality of Life (HrQoL) was qualitatively examined and needs for care from the young patients and their parents perspective were identified. Methods: Focus group discussions with 26 American-English speaking and nine American-Spanish speaking children and their parents were conducted, transcribed verbatim and subsequently qualitatively analyzed by two independent raters, using an existing coding guideline, based on the multidimensional HrQoL concept and a special software (VERBI-Software MAXQDA 10). Results: A total of 1313 statements for the English-speaking and 447 statements for the Spanish-speaking families were categorized. In the US, the strongest frequency of mention was found for the HrQoL dimension “Social” across respondents, followed by “Treatment” and “Emotion”. Conclusion: Conducting and analyzing data generated from focus groups ensure that young patients’ experiences of disease are represented in the measure of outcomes for use in clinical trials and patient care.

Acromicric dysplasia caused by a mutation of fibrillin 1 in a family:A case report

BACKGROUND Acromicric dysplasia(AD)is a rare skeletal dysplasia.Its incidence is<1/1000000,and only approximately 60 cases are reported worldwide.It is a disease characterized by severe short stature,short hands and feet,facial abnormalities,normal intelligence,and bone abnormalities.Unlike other skeletal dysplasia,AD has a mild clinical phenotype,mainly characterized by short stature.Extensive endocrine examination has not revealed a potential cause.The clinical effect of growth hormone therapy is still uncertain.CASE SUMMARY We report a clinical phenotype of AD associated with mutations in the fibrillin 1(FBN1)(OMIM 102370)gene c.5183C>T(p.Ala1728Val)in three people from a Chinese family.A 4-year-old member of the family first visited the hospital because of slow growth and short stature for 2 years,but no abnormalities were found after a series of laboratory tests,echocardiography,pituitary magnetic resonance imaging,and ophthalmological examination.Recombinant human growth hormone(rhGH)was used to treat the patient for>5 years.The efficacy of rhGH was apparent in the first year of treatment;the height increased from-3.64 standard deviation score(SDS)to-2.88 SDS,while the efficacy weakened from the second year.However,long-term follow-up is required to clarify the efficacy of rhGH.CONCLUSION FBN1-related AD has genetic heterogeneity and/or clinical variability,which brings challenges to the evaluation of clinical treatment.rhGH is effective for treatment of AD,but long-term follow-up is needed to clarify the effect.

Secular Change in Stature of Urban Chinese Children and Adolescents, 1985-2010

Objective Research evidence shows a secular trend in Chinese physical growth in recent years.The aim of this study was to analyze and assess changes in stature of children and adolescents during the 25 years from 1985‐2010,using national data.Methods Data came from successive cycles of the Chinese National Survey on Students＇ Constitution and Health（CNSSCH）.Subjects were 7‐ to 18‐year‐old children and adolescents.Results An overall positive secular trend occurred in urban China during 1985‐2010.The overall average rates of increment were 2.4 and 1.7 cm/decade for boys and girls,respectively.Total increases in adult stature for boys and girls were 2.6 and 1.7 cm,yielding rates of 1.0 and 0.7 cm/decade,respectively.Cities with different socioeconomic levels had different characteristic trends.Mean stature increases in big cities were larger than those in moderate and small cities,and boys and girls in moderate and small cities showed greater potential for growth in stature.Conclusion An overall positive secular growth trend was associated with socioeconomic progress and differed with area socioeconomic levels.School policies and strategies should be developed based on increased stature,and should continue narrowing the inequity between different socioeconomic populations.

Secular Changes of Stature in Rural Children and Adolescents in China, 1985-2010

Objective To analyze and assess secular change in stature in rural children and adolescents in China from 1985 to 2010. Methods Data were obtained from the 6 rounds of the Chinese National Survey on Student＇s Constitution and Health. The subjects enrolled in the study were children and adolescents aged 7-18 years in rural areas of provincial capitals. Results An overall positive secular trend in stature occurred in rural areas of provincial capitals in China from 1985 to 2010. The overall average increase rates were 3.1 and 2.4 cm/decade for boys and girls, respectively. The total body height increases for grown up boys and girls were 3.6 and 2.3 cm and the increase rates were 1.4 and 0.9 cm/decade, respectively. There were differences in body height increase among eastern, central and western regions. The average body height of the children or adolescents in eastern region was highest, followed by central region and western region. The overall increase rates in central region were highest among the three regions. The difference between eastern/central region and western region was obvious. 〈br〉 Conclusion Positive secular trend in stature of children or adolescents has occurred in rural area of China, and rural boys and girls showed a great potential for continuous growth. More attention should be paid to the differences in children＇s body height between western region and eastern/central region.

Blood pressure and stature in Helicobacter pylori positive and negative persons

To evaluate vital signs and body indices in Helicobacter pylori (H. pylori) positive and negative persons. A total of 22 centres entered the study. They were spread over the whole country, corresponding well to the geographical distribution of the Czech population. A total of 1818 subjects (aged 5-98 years) took part in the study, randomly selected out of 38147 subjects. H. pylori infection was investigated by means of a 13C-urea breath test. Data on height, weight, systolic and diastolic blood pressure and heart rate were collected at the clinics of general practitioners. The overall prevalence of H. pylori infection was 30.4% (402/1321) in adults (≥ 18 year-old) and 5.2% (26/497) in children and adolescents (≤ 17 year-old). Once adjusted for age and gender, only a difference in body mass index remained statistically significant with H. pylori positive adults showing an increase of 0.6 kg/m2 in body mass index. Once adjusted for age and gender, we found a difference in height between H. pylori positive and H. pylori negative children and adolescents. On further adjustment for place of residence, this difference became statistically significant, with H. pylori positive children and adolescents being on average 3.5 cm shorter. H. pylori positive adults were significantly older compared to H. pylori negative subjects. Once adjusted for age and gender, H. pylori infection had no impact on body weight, body mass index and vital signs either in adults or children and adolescents. Chronic H. pylori infection appeared to be associated with short stature in children. H. pylori infection did not influence blood pressure, body weight and body mass index either in adults or children and adolescents.

Geleophysic dysplasia caused by a mutation in FBN1:A case report

BACKGROUND Geleophysic dysplasia(GD)presents the characterized clinical manifestations of acromelic dysplasia,including extremely short stature,short limbs,small hands and feet,stubby fingers and toes,joint stiffness and others.It is clinically distinct from the other acromelic dysplasia in terms of symptoms such as cardiac valvular abnormalities,progressive hepatomegaly and tracheal stenosis.CASE SUMMARY We report on a Chinese 9-year-old girl with GD with the c.5243G>T(p.C1748F)mutation in FBN1(fibrillin 1,OMIM 134797).She was born in Guangxi Zhuang Autonomous Region of China.The patient presented with typical clinical features of GD and recurrent respiratory tract infections over 6 years.Laboratory studies and chest computed tomography(CT)scan indicated bronchopneumonia.Her echocardiography revealed mild mitral valve thickening with regurgitation.Laryngopharyngeal CT and electronic bronchoscopy revealed severe glottic stenosis.Echocardiography examination displayed mild mitral valve thickening and regurgitation.Ophthalmic examination did not reveal myopia or lens dislocation.Treated with ceftriaxone sodium and methylprednisolone sodium succinate for injection as well as methylprednisolone orally,patient’s symptoms had improved.CONCLUSION GD is a rare genetic condition that can cause life-threatening cardiovascular and respiratory problems.This study also found that the identified genotype of GD could be related to different clinical phenotypes.

Burden of celiac disease in the Mediterranean area

AIM: To estimate the burden of undiagnosed celiac disease (CD) in the Mediterranean area in terms of morbidity, mortality and health cost. METHODS: For statistics regarding the population of each country in the Mediterranean area, we accessed authoritative international sources (World Bank, World Health Organization and United Nations). The prevalence of CD was obtained for most countries from published reports. An overall prevalence rate of 1% cases/total population was finally estimated to represent the frequency of the disease in the area, since none of the available conf idence intervals of the reported rates significantly excluded this rate. The distribution of symptoms and complications was obtained from reliable reports in the same cohort. A standardized mortality rate of 1.8 was obtained from recent reports. Crude health cost was estimated for the years between symptoms and diagnosis for adults and children, and was standardized for purchasing power parity to account for the different economic prof iles amongst Mediterranean countries. RESULTS: In the next 10 years, the Mediterranean area will have about half a billion inhabitants, of which 120 million will be children. The projected number of CD diagnoses in 2020 is 5 million cases (1 million celiac children), with a relative increase of 11% compared to 2010. Based on the 2010 rate, there will be about 550 000 symptomatic adults and about 240 000 sick children: 85% of the symptomatic patients will suffer from gastrointestinal complaints, 40% are likely to have anemia, 30% will likely have osteopenia, 20% of children will have short stature, and 10% will have abnormal liver enzymes. The estimated standardized medical costs for symptomatic celiac patients during the delay between symptom onset and diagnosis (mean 6 years for adults, 2 years for children) will be about €4 billion (€387 million for children) over the next 10 years. A delay in diagnosis is expected to increase mortality: about 600 000 celiac patients will die in the next 10 years, with an excess of 44.4% vs age-and sexmatched controls. CONCLUSION: In the near future, the burden of CD will increase tremendously. Few Mediterranean countries are able to face this expanding epidemic alone.

Recognizable type of pituitary, heart, kidney and skeletal dysplasia mostly caused by SEMA3A mutation: A case report

BACKGROUND The SEMA3A gene,which is located at 7q21.11,is involved in hypothalamic neuron migration,heart development,kidney development,and skeleton metabolism.Mutation of the SEMA3A gene is associated with Kallmann syndrome 16 with or without a normal sense of smell.In addition,two case reports showed that mutation of the SEMA3A gene could cause short stature,low gonadotropin,hypogonadism,thoracic deformity,a high scapula,rib and lower limb deformity,facial deformity(long face,epicanthic folds,backwards ears),and arterial malformation.CASE SUMMARY We reported the case of a 26-year-old Chinese man who was admitted because of short stature.Physical examination showed that he had many abnormal symptoms,including a short neck,facial moles,knee valgus,transverse palm,continuous grade 5/6 murmurs in the pulmonary auscultation area,no whiskers,or pubic hair,no Adam’s apple,short penis and cryptorchidism.Radiological examination showed pituitary,gonad,heart,kidney and skeletal dysplasia.The laboratory tests revealed low growth hormone,luteinizing hormone,folliclestimulating hormone,testosterone and estrogen.Clinical whole-exome detection showed that our patient,unlike previously reported patients,has a new SEMA3A gene mutation(c.950A>G).Now,his height has increased by 3 cm.In addition,he has a good appetite and reduced subcutaneous fat over 3 mo of recombinant human growth hormone injections therapy.Unfortunately,he refuses further treatment about gonad.CONCLUSION Patients who come to a hospital because of their short stature must undergo gene detection if they have other simultaneous abnormal phenotypes.

Short stature associated with a novel mutation in the aggrecan gene:A case report and literature review

BACKGROUND Mutations in the aggrecan(ACAN)gene are identified in patients with:spondyloepiphyseal dysplasia,Kimberley type;short stature with advanced bone age(BA);in the presence or absence of heterozygous ACAN mutation-induced early-onset osteoarthritis and/or osteochondritis dissecans;and spondyloepimetaphyseal dysplasia,ACAN type.Heterozygous mutations contribute to spondyloepiphyseal dysplasia,Kimberley type(MIM#608361),which is a milder skeletal dysplasia.In contrast,homozygous mutations cause a critical skeletal dysplasia,which is called spondyloepimetaphyseal dysplasia,ACAN type(MIM#612813).Lately,investigations on exome and genome sequencing have shown that ACAN mutations can also lead to idiopathic short stature with or without an advanced BA,in the presence or absence of early-onset osteoarthritis and/or osteochondritis dissecans(MIM#165800).We herein reported a heterozygous defect of ACAN in a family with autosomal dominant short stature,BA acceleration,and premature growth cessation.CASE SUMMARY A 2-year-old male patient visited us due to growth retardation.The patient presented symmetrical short stature(height 79 cm,<-2 SD)without facial features and other congenital abnormalities.Whole-exome sequencing revealed a heterozygous pathogenic variant c.871C>T(p.Gln291*)of ACAN,which was not yet reported in cases of short stature.This mutation was also detected in his father and paternal grandmother.According to the Human Gene Mutation Database,67 ACAN mutations are registered.Most of these mutations are genetically inheritable,and very few children with short stature are associated with ACAN mutations.To date,heterozygous ACAN mutations have been reported in approximately 40 families worldwide,including a few individuals with a decelerated BA.CONCLUSION Heterozygous c.871C>T(p.Gln291*)variation of the ACAN gene was the disease-causing variant in this family.Collectively,our newly discovered mutation expanded the spectrum of ACAN gene mutations.

The Wingate anaerobic test cannot be used for the evaluation of growth hormone secretion in children with short stature

Purpose: To assess the growth hormone(GH) response to the Wingate anaerobic test(WAn T) among children with short stature and suspected GH deficiency. We hypothesized that the GH response to the WAn T would be similar to the GH response to a commonly used pharmacologic provocation test.Methods: Ten children(6 males and 4 females, age range 9.0–14.9 years) participated in the study. Each participant performed 2 tests: a standard all-out WAn T, cycling for 30 s against constant resistance, and a standardized pharmacologic test(clonidine or glucagon). Blood samples for GH were collected before and 10, 30, 45, and 60 min after the beginning of exercise. In addition, we collected pre-and post-exercise blood lactate levels.Results: There was a significant increase in GH levels after the WAn T, yet in 9 of 10 participants, this increase was below the threshold for GH sufficiency. Peak GH after the WAn T was significantly lower compared to the pharmacologic GH provocation tests(with 9 of 10 demonstrating GH-sufficient response).Conclusion: The traditional WAn T cannot be used as a GH provocation test. Further research is needed to develop anaerobic exercise protocols sufficient to promote GH secretion.

Growth hormone therapy for children with KBG syndrome:A case report and review of literature

BACKGROUND The incidence of short stature in KBG syndrome is relatively high.Data on the therapeutic effects of growth hormone(GH)on children with KBG syndrome accompanied by short stature in the previous literature has not been summarized.CASE SUMMARY Here we studied a girl with KBG syndrome and collected the data of children with KBG syndrome accompanied by short stature from previous studies before and after GH therapy.The girl was referred to our department because of short stature.Physical examination revealed mild dysmorphic features.The peak GH responses to arginine and clonidine were 6.22 and 5.40 ng/mL,respectively.The level of insulin-like growth factor 1(IGF-1)was 42.0 ng/mL.Genetic analysis showed a c.2635 dupG(p.Glu879fs)mutation in the ANKRD11 gene.She received GH therapy.During the first year of GH therapy,her height increased by 0.92 standard deviation score(SDS).Her height increased from-1.95 SDS to-0.70 SDS after two years of GH therapy.There were ten children with KBG syndrome accompanied by short stature who received GH therapy in reported cases.Height SDS was improved in nine(9/10)of them.The mean height SDS in five children with KBG syndrome accompanied by short stature increased from-2.72±0.44 to-1.95±0.57 after the first year of GH therapy(P=0.001).There were no adverse reactions reported after GH treatment.CONCLUSION GH treatment is effective in our girl and most children with KBG syndrome accompanied by short stature during the first year of therapy.

Costello Syndrome with Congenital Pulmonary Valve Stenosis and Ventriculomegaly—A Case Report

Costello syndrome is an extremely rare genetic disorder with growth delay after birth and typically results in short stature during childhood. It is one of the RASopathy of Ras/MAPK pathway syndromes. It affects the transforming protein p21, an enzyme that in humans is encoded by the HRAS gene. H-Ras is a small G protein and once bound to Guanosine triphosphate, it will activate a Raf kinase like C-Raf, the next step in the MAPK/ERK pathway (mitogen-actvated protein kinase/extracellular signal-regulated kinase) i.e., MEK (mitogen-actvated ERK kinase), a protein that phosphorylate ERK which can directly and indirectly activate many transcription factors. This pathway is also known as Ras-Raf, MEK-ERK pathway, which is a chain of proteins on the cell that communicate a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. Activation of ERK 1/2 is involved in signal transduction pathways associated with cardiac hypertrophy. The developmental syndromes caused by germline mutations in genes that alter the RAS components of the MAP/ERK signal transduction pathway are called “RASopathies”. Cardiovascular abnormalities are important features of Costello syndrome and other RASopathies such as Noonan syndrome. Background of this case report described the congenital valvular pulmonic stenosis and ventriculomegaly associated with Costello syndrome by transthoracic echocardiographic imaging in a 9-year-old male boy.

A 36 Mb terminal deletion of chromosome 2BL is responsible for a wheat semi-dwarf mutation

Reduced plant height is one of the most important traits related to lodging resistance and crop yield. The use of reduced height genes has been one of the main features in breeding modern high-yielding wheat varieties with less lodging. A spontaneous dwarf mutant DD399 was identified in a high yielding, gibberellic acid(GA)-insensitive, lodging-resistant variety Nongda 399(ND399). Significant differences in upper internode lengths between mutant DD399 and wild type ND399 were caused by reduced cell elongation. The plant height of ND399 × DD399 F_(1) hybrids was intermediate between the parents, indicating incomplete dominance or a dose–response effect of a reduced height gene. Plant height showed continuous distribution in the F_(2) population, and segregation distortion was observed among the 2292 F_(2:3) progenies. The reduced height mutation was characterized by Illumina 90 K iSelect SNP genotyping and bulked segregant RNA-Seq(BSR-Seq) analysis of the segregating population. A concentrated cluster of polymorphic SNPs associated with the reduced height phenotype was detected in the distal region of chromosome arm 2 BL. Co-segregation of reduced height phenotype with the clustered markers revealed a 36 Mb terminal deletion of chromosome 2 BL in mutant DD399.

Change in stature by walking and running at a preferred transition speed

This study aimed to measure stature changes during and after walking and running at a preferred transition speed (PTS) and the recovery period, and to examine differences caused by loads imposed on the spinal column. Seven males and three females aged 22-41 years took part in this study. Subjects The subjects underwent 15 minutes of walking or running on a treadmill in a random order. Stature changes were measured during each exercise at intervals of 5 minutes and after a 20 minute standing recovery period within units of 0.01 mm. Two- way ANOVA revealed that both main factors, gait (F = 5.250, P < 0.05) and elapsed time (F = 14.409, P < 0.05), had a significant effect on stature. In the post hoc test, stature shrank with time and its loss was found to be greater in running than in walking, but recovered after both exercises. In conclusion, the spinal load increases with time during both walking and running at PTS, but is greater in running than in walking. After both exercises, spinal shrinkage shows a similar recovery process and recovers faster in walking to its pre-exercise level.

MEASUREMENTS OF URINARY HUMAN GROWTH HORMONE IN SUBJECTS WITH NORMAL AND ABNORMAL GROWTH:A CRITICAL OF ITS POTENTIAL CLINICAL UTILITY

Ovrmight urinary human growth hormone (HGH) levels in 53 normal growthprepuberty children,38 primary short stature chjildren ahildren them 11 cases with GH defi-ciency (GHD), 27 cases with normal GH reset to the conveatnd pharmacutical provocative tests diagnosed as idiopathic growth failure or non-GHD short children and 3adults with acromegaly were measured by the LAB-ELISA technique,The levelsdemonstrated stable in normal growth prepubertal children,but significantly rasised inacromegaly,and decreased in GHD,and in non=GHD short children,Thus,the resultsshow that measurement of urinary HGH being useful for Jiagnosis of GHD and forscreening the non-GHD growth failure.

Detection of short stature homeobox 2 and RAS-associated domain family 1 subtype A DNA methylation in interventional pulmonology

One of the most important aspects of interventional pulmonology is to obtain tissue or liquid samples of the chest to diagnose a respiratory disease;however,it is still possible to obtain insufficient tissue or cytologic specimens.Indeed,methylation detection is an effective method by which to establish a diagnosis.This review focuses on the clinical application of short stature homeobox 2 and RAS-associated domain family 1 subtype A DNA methylation detection in interventional pulmonology,including bronchoscopic fluid biopsy,transbronchial needle aspiration,and pleural effusion.

An Assessment of Predisposing Factors of Atherogenic Dyslipidemia in an Urban Pediatric Population in Cameroon

Background: Dyslipidemia in childhood contributes to an increased risk of cardiovascular diseases later in life. This study sets out to determine the prevalence of dyslipidemia and describe the associations between selected variables and dyslipidemia in Cameroon urban children. Methods: This cross-sectional hospital-based study included 415 children (188 boys and 227 girls) between the ages of 5 and 16 years. Dyslipidemia was defined as an abnormal value of one or more of the following lipids: Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Percentage body fat (%BF) was estimated using bio-electric impedance analysis. A structured questionnaire was used by parents to report physical activity, screen time and eating habits of the children. Relationships between predictors and dyslipidemia were assessed using multiple binary logistic regression analyses. Results: The prevalence of dyslipidemia was 46.0%. Dyslipidemic children had significantly higher %BF, TG and LDL-C and lower HDL-C than the normal children (p p = 0.004), short stature (OR 2.8, 95% CI 1.1 - 6.8, p = 0.041), physical activity p Conclusion: This study confirms that obesity, short stature, physical activity < 60 minutes/day and never/occasional consumption of fruits/vegetables were associated with dyslipidemia. Also, a high proportion of children had one or more lipid disorders. This is concerning and indicates the importance of assessing dyslipidemia in pre-school children in future studies.

Short Stature due to Ectopic Neurohypophysis: Case Report

Ectopic posterior pituitary is a disruption in the normal embryogenesis and is one of the rare but common causes of pituitary dwarfism. We report the MRI and clinical findings of a 13.5-year-old Saudi boy who was referred to the endocrine outpatient clinic with no significant complaints except for fatigue, exercise intolerance and short stature. Physical examination revealed short stature (below 2nd centile) with normal body proportion without any dysmorphic features and prepubertal secondary sexual characteristics and genitalia. Hormonal profile revealed: low thyroxine level, low gonadotrophins, low testosterone, low cortisol and blunted growth hormone (GH) response to insulin induced hypoglycaemia. Bone age was of 5 years old. The MRI result concluded with a diagnosis of ectopic posterior pituitary. A diagnosis of posterior pituitary ectopia (PPE) with panhypopituitarism was made.

Growth Hormone Treatment, Cardiovascular Risk and Autonomic Maturation in Children and Adolescents with Growth Hormone Deficiency or Born Small for Gestational Age

Introduction: The impact of growth hormone therapy in children with short stature on cardiovascular prognosis seems to be unpredictable from big databases. The enhanced cardiovascular risk in this group of patients may be related to adverse autonomic imprinting by early life stress. Autonomic dysfunction and possible effects of growth hormone therapy on the autonomic nervous system can be measured easily by calculating heart rate variability (HRV) from Holter electrocardiogram monitoring. Methods: We performed HRV analysis prior to growth hormone therapy (N = 33), within the first year of growth hormone therapy between 4 and 10 years of age (N = 19), at least a further HRV measurement between 10 and 15 years (N = 30). Additional measurements were performed before and after cessation of growth hormone therapy (N = 14). Data were compared to untreated pediatric patients with short stature and to age matched healthy controls. Results: Untreated patients with short stature due to growth hormone deficiency or intrauterine growth restriction in early childhood have significantly increased heart rates most of all at night and concomitantly reduced global HRV indicated as Standard Deviation of Normal to Normal Intervals (SDNN). Growth hormone treated adolescents and the untreated patients with short stature show significantly elevated mean heart rates and concomitantly reduced vagus activities measured as reduced Route Mean Square Standard Deviation (RMSSD). After cessation of growth hormone treatment SDNN significantly increases and heart rate decreases to normal values in formerly treated patients with catch-up growth. Conclusion: There is a comparable autonomic dysfunction in treated and untreated children with short stature as an indicator for enhanced cardiovascular risk. After cessation of growth hormone therapy, we found a significant improvement of reduced HRV to normal values.

Strength, But Not Direction, of Handedness Is Related to Height

Left-handers are reputed to be shorter than right-handers. However, previous research has confounded handedness direction (left-versus right-handedness) with handedness strength (consistency with which one hand is chosen across a variety of tasks;consistent-versus inconsistent-handedness). Here, we support a relationship between handedness strength, but not direction, and stature, with increasing inconsistent-handedness associated with increasing self-reported height.