scholarly journals Towards a Rational and Efficient Diagnostic Approach in Children Referred for Growth Failure to the General Paediatrician

2019 ◽  
Vol 91 (4) ◽  
pp. 223-240 ◽  
Author(s):  
Jan M. Wit ◽  
Gerdine A. Kamp ◽  
Wilma Oostdijk ◽  
Keyword(s):  
Short Stature ◽  
Diagnostic Yield ◽  
Secondary Growth ◽  
Growth Failure ◽  
Bone Age ◽  
Bone Diseases ◽  
Diagnostic Approach ◽  
Hormone Deficiency ◽  
Growth Disorders ◽  
Metabolic Bone Diseases

Based on a recent Dutch national guideline, we propose a structured stepwise diagnostic approach for children with growth failure (short stature and/or growth faltering), aiming at high sensitivity for pathologic causes at acceptable specificity. The first step is a detailed clinical assessment, aiming at obtaining relevant clinical clues from the medical history (including family history), physical examination (emphasising head circumference, body proportions and dysmorphic features) and assessment of the growth curve. The second step consists of screening: a radiograph of the hand and wrist (for bone age and assessment of anatomical abnormalities suggestive for a skeletal dysplasia) and laboratory tests aiming at detecting disorders that can present as isolated short stature (anaemia, growth hormone deficiency, hypothyroidism, coeliac disease, renal failure, metabolic bone diseases, renal tubular acidosis, inflammatory bowel disease, Turner syndrome [TS]). We advise molecular array analysis rather than conventional karyotyping for short girls because this detects not only TS but also copy number variants and uniparental isodisomy, increasing diagnostic yield at a lower cost. Third, in case of diagnostic clues for primary growth disorders, further specific testing for candidate genes or a hypothesis-free approach is indicated; suspicion of a secondary growth disorder warrants adequate further targeted testing.

scholarly journals Three years of growth hormone therapy in children born small for gestational age: results from the ANSWER Program

2018 ◽  
Vol 7 (10) ◽  
pp. 1096-1104 ◽  
Author(s):  
Robert Rapaport ◽  
Peter A Lee ◽  
Judith L Ross ◽  
Paul Saenger ◽  
Vlady Ostrow ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Growth Failure ◽  
Hormone Deficiency ◽  
Birth Size ◽  
Growth Disorders ◽  
Gh Therapy ◽  
The Impact

Growth hormone (GH) is used to treat short stature and growth failure associated with growth disorders. Birth size and GH status variably modulate response to GH therapy. The aim of this study was to determine the effect of birth size on response to GH therapy, and to determine the impact of GH status in patients born small for gestational age (SGA) on response to GH therapy. Data from the prospective, non-interventional American Norditropin Studies: Web-Enabled Research (ANSWER) Program was analyzed for several growth outcomes in response to GH therapy over 3 years. GH-naïve children from the ANSWER Program were included in this analysis: SGA with peak GH ≥10 ng/mL (20 mIU/L), SGA with peak GH <10 ng/mL (20 mIU/L), isolated growth hormone deficiency (IGHD) born SGA, IGHD not born SGA and idiopathic short stature. For patients with IGHD, those who did not meet criteria for SGA at birth showed greater improvements in height SDS and BMI SDS than patients with IGHD who met criteria for SGA at birth. For patients born SGA, response to GH therapy varied with GH status. Therefore, unlike previous guidelines, we recommend that GH status be established in patients born SGA to optimize GH therapy.

scholarly journals Síndrome de Klinefelter con deficiencia parcial de hormona de crecimiento.

2015 ◽  
Vol 10 (1) ◽  
pp. 38
Author(s):  
Carlos TORI TORI ◽  
Carlos ROE B.
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Short Stature ◽  
Klinefelter Syndrome ◽  
Bone Age ◽  
Hormone Deficiency ◽  
Klinefelter’S Syndrome ◽  
Klinefelter's Syndrome ◽  
The Third ◽  
Rare Association

We present a case of Klinefelter’s syndrome and short stature due to partial growth hormone deficiency. His height was below the third percentile for age and his bone age lagged behind four years. Cases like this are generally due to the presence of a an isochromosome Xq or to an isolated partial or total deficiency of growth hormone, or to partial or panhypopituitarism. We wish de emphasize the rare association between Klinefelter syndrome and growth hormone deficiency.

scholarly journals Balanced assessment of growth disorders using clinical, endocrinological, and genetic approaches

2021 ◽  
Vol 26 (4) ◽  
pp. 218-226
Author(s):  
Martin Oswald Savage ◽  
Helen Louise Storr
Keyword(s):  
Short Stature ◽  
Clinical Skills ◽  
Unknown Origin ◽  
Hormone Deficiency ◽  
Candidate Gene Approach ◽  
Growth Disorders ◽  
Monogenic Disorders ◽  
Balanced Assessment ◽  
Equal Importance ◽  
Genetic Probes

Determining the pathogenesis of pediatric growth disorders is often challenging. In many cases, no pathogenesis is identified, and a designation of idiopathic short stature is used. The investigation of short stature requires a combination of clinical, endocrinological, and genetic evaluation. The techniques used are described, with equal importance being given to each of the 3 approaches. Clinical skills are essential to elicit an accurate history, family pedigree, and symptoms of body system dysfunction. Endocrine assessment requires hormonal determination for the diagnosis of hormone deficiency and initiation of successful replacement therapy. Genetic analysis has added a new dimension to the investigation of short stature and now uses next-generation sequencing with a candidate gene approach to confirm probable recognizable monogenic disorders and exome sequencing for complex phenotypes of unknown origin. Using the 3 approaches of clinical, endocrine, and genetic probes with equal status in the hierarchy of investigational variables provides the clinician with the highest chance of identifying the correct causative pathogenetic mechanism in a child presenting with short stature of unknown origin.

scholarly journals Aggrecanopathies highlight the need for genetic evaluation of ISS children

2020 ◽  
Vol 183 (2) ◽  
pp. C9-C10
Author(s):  
Ola Nilsson
Keyword(s):  
Short Stature ◽  
Osteochondritis Dissecans ◽  
Early Onset ◽  
Gene Mutations ◽  
Bone Age ◽  
Genetic Evaluation ◽  
Large Cohort ◽  
Growth Disorders ◽  
Common Causes ◽  
Work Up

Short stature is one of the most common causes for referrals to pediatric endocrinologists. However, in a majority of the children, no underlying cause can be identified and the child instead receives the unhelpful diagnosis of idiopathic short stature (ISS), often after extensive work-up and testing. Recent advances in genetic methodology have allowed for the identification of a number of different monogenic conditions within the large cohort of ISS children. Isolated short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans (MIM#165800) due to heterozygous aggrecan gene mutations exemplifies how this progress is changing the way we assess, counsel and treat children with non-endocrine growth disorders.

scholarly journals Novel Mutations and Genes That Impact on Growth in Short Stature of Undefined Aetiology: The EPIGROW Study

2020 ◽  
Vol 4 (10) ◽  
Author(s):  
Reena Perchard ◽  
Philip George Murray ◽  
Antony Payton ◽  
Georgina Lee Highton ◽  
Andrew Whatmore ◽  
...  
Keyword(s):  
Short Stature ◽  
Sequence Data ◽  
Diagnostic Yield ◽  
Growth Disorders ◽  
Supporting Evidence ◽  
Missense Mutations ◽  
Nucleotide Polymorphisms ◽  
Variant Of Uncertain Significance ◽  
Uncertain Significance ◽  
The Difference

Abstract Background Children with short stature of undefined aetiology (SS-UA) may have undiagnosed genetic conditions. Purpose To identify mutations causing short stature (SS) and genes related to SS, using candidate gene sequence data from the European EPIGROW study. Methods First, we selected exonic single nucleotide polymorphisms (SNPs), in cases and not controls, with minor allele frequency (MAF) &lt; 2%, whose carriage fitted the mode of inheritance. Known mutations were identified using Ensembl and gene-specific databases. Variants were classified as pathogenic, likely pathogenic, or variant of uncertain significance using criteria from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. If predicted by ≥ 5/10 algorithms (eg, Polyphen2) to be deleterious, this was considered supporting evidence of pathogenicity. Second, gene-based burden testing determined the difference in SNP frequencies between cases and controls across all and then rare SNPs. For genotype/phenotype relationships, we used PLINK, based on haplotype, MAF &gt; 2%, genotype present in &gt; 75%, and Hardy Weinberg equilibrium P &gt; 10–4. Results First, a diagnostic yield of 10% (27/263) was generated by 2 pathogenic (nonsense in ACAN) and a further 25 likely pathogenic mutations, including previously known missense mutations in FANCB, IGFIR, MMP13, NPR2, OBSL1, and PTPN11. Second, genes related to SS: all methods identified PEX2. Another 7 genes (BUB1B, FANCM, CUL7, FANCA, PTCH1, TEAD3, BCAS3) were identified by both gene-based approaches and 6 (A2M, EFEMP1, PRKCH, SOS2, RNF135, ZBTB38) were identified by gene-based testing for all SNPs and PLINK. Conclusions Such panels improve diagnosis in SS-UA, extending known disease phenotypes. Fourteen genes related to SS included some known to cause growth disorders as well as novel targets.

scholarly journals Towards a Rational and Efficient Diagnostic Approach in Children Referred for Tall Stature and/or Accelerated Growth to the General Paediatrician

2019 ◽  
Vol 91 (5) ◽  
pp. 293-310
Author(s):  
Peter Lauffer ◽  
Gerdine A. Kamp ◽  
Leonie A. Menke ◽  
Jan M. Wit ◽  
Wilma Oostdijk ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Klinefelter Syndrome ◽  
Pubertal Development ◽  
Secondary Growth ◽  
Diagnostic Approach ◽  
Skeletal Maturation ◽  
Growth Disorders ◽  
Tall Stature ◽  
General Paediatrician ◽  
Accelerated Growth

Tall stature and/or accelerated growth (TS/AG) in a child can be the result of a primary or secondary growth disorder, but more frequently no cause can be found (idiopathic TS). The conditions with the most important therapeutic implications are Klinefelter syndrome, Marfan syndrome and secondary growth disorders such as precocious puberty, hyperthyroidism and growth hormone excess. We propose a diagnostic flow chart offering a systematic approach to evaluate children referred for TS/AG to the general paediatrician. Based on the incidence, prevalence and clinical features of medical conditions associated with TS/AG, we identified relevant clues for primary and secondary growth disorders that may be obtained from the medical history, physical evaluation, growth analysis and additional laboratory and genetic testing. In addition to obtaining a diagnosis, a further goal is to predict adult height based on growth pattern, pubertal development and skeletal maturation. We speculate that an improved diagnostic approach in addition to expanding use of genetic testing may increase the diagnostic yield and lower the age at diagnosis of children with a pathologic cause of TS/AG.

scholarly journals SAT-LB14 Anthropometry and Vertebral Abnormality in Children With Transfusion-Dependent Thalassemia in Phramongkutklao Hospital, Bangkok, Thailand

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nawachai Lertvivatpong ◽  
Voraluck Phatarakijnirund
Keyword(s):  
Short Stature ◽  
Adult Height ◽  
Screening Program ◽  
Multivariate Logistic Regression Analysis ◽  
Growth Failure ◽  
Bone Age ◽  
Team Approach ◽  
Z Score ◽  
Lower Segment ◽  
Tertiary Center

Abstract Anthropometry and vertebral abnormality in Children with Transfusion-dependent Thalassemia in Phramongkutklao HospitalBackgrounds: Thalassemia is an untreatable inherited hematologic disorder, unless stem cell transplantation, characterized by anemia from decreased hemoglobin production. Growth failure is one of the most common endocrine dysfunction in children with transfusion-dependent thalassemia (TDT) Objective: To evaluate the prevalence and associated factors of anthropometry and vertebral abnormality in transfusion-dependent thalassemia (TDT) children in a single tertiary center. Method: A cross-sectional study was conducted in transfusion dependent thalassemia patients who had visited in pediatric hematology clinic during 1st January 2018 to 31st December 2019. Collaborators had examined by history taking, physical examinations, laboratory and radiology reviewed. Results: Eighty-one collaborators were enrolled. Mean age was 13.7 ± 6.4 years and 46 of them (56.8%) were male. Pre-transfusion Hb and serum ferritin were 8.0 ± 1.0 g/dL and 1,562 + 1,394 ng/mL, respectively. Twenty-one (25.9%) had short stature determined by predicted adult height (PAH) below target adult height (TAH), 27(33.3%) had decreased upper-lower segment ratio for and 21 (26%) had BMI z-score below -2SD for age. Delay puberty was found in 13.2% of patients. Radiological examinations revealed delayed bone age of 4.9% and osteopenia of 25.9% whereas no vertebral fracture was documented. In multivariate logistic regression analysis (backward Wald), Serum ALP (p=0.009), mean pre-transfusion hemoglobin &lt;9 g/dL (p&lt;0.001), osteopenia (p=0.05) and delay bone age (p=0.019) were associated with PAH below TAH. Duration of chelation (p=0.013) and osteopenia (p=0.015) were associated with decreased upper-lower segment ratio. Low serum calcium (p=0.009), high serum phosphate (p=0.04) and impaired fasting glucose (p=0.004) were associated with BMI z-score below -2SD for age. Conclusions: Anthropometry abnormalities, including short stature, abnormal upper-lower segment ratio and low BMI, are common in TDT children. However, no vertebral abnormality was found in this study. Routine screening program by multidisciplinary team approach should be applied in thalassemia children.Keywords: Thalassemia major, endocrinopathies, growth failure, short stature, body disproportion

Metabolic disease of skeleton and inherited disorders

2011 ◽  
Author(s):  
Paul Wordsworth
Keyword(s):  
Metabolic Disease ◽  
Short Stature ◽  
Bone Disease ◽  
Bone Diseases ◽  
Genetic Mutations ◽  
Inherited Disorders ◽  
Ehlers Danlos Syndrome ◽  
Metabolic Bone Diseases ◽  
Metabolic Bone ◽  
Danlos Syndrome

♦ Classic metabolic bone diseases include osteoporosis, osteomalacia, Paget’s disease, and parathyroid bone disease♦ Heritable disorders of the skeleton include numerous osteochrondrodysplasias, Marfan syndrome, and Ehlers-Danlos syndrome♦ Investigation of short stature is indicated for those below 0.4 percentile, with skeletal disproportion and/or progressive shortness♦ Genetic mutations for most of these conditions have been identified but clinical/radiographic features are usually diagnostic.

scholarly journals The prevalence and volumetry of pituitary cysts in children with growth hormone deficiency and idiopathic short stature

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Nicholas Krasnow ◽  
Bradley Pogostin ◽  
James Haigney ◽  
Brittany Groh ◽  
Winston Weiler ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Short Stature ◽  
Growth Failure ◽  
Brain Magnetic Resonance Imaging ◽  
Idiopathic Short Stature ◽  
Hormone Deficiency ◽  
Gh Treatment ◽  
Cyst Volume ◽  
Pituitary Cysts

AbstractBackgroundPituitary cysts have been speculated to cause endocrinopathies. We sought to describe the prevalence and volumetry of pituitary cysts in patients with growth hormone deficiency (GHD) and idiopathic short stature (ISS).MethodsSix hundred and eighteen children evaluated for growth failure at the Division of Pediatric Endocrinology at New York Medical College between the years 2002 and 2012, who underwent GH stimulation testing and had a brain magnetic resonance imaging (MRI) prior to initiating GH treatment were randomly selected to be a part of this study. High resolution MRI was used to evaluate the pituitary gland for size and the presence of a cyst. Cyst prevalence, cyst volume and percentage of the gland occupied by the cyst (POGO) were documented.ResultsFifty-six patients had a cyst, giving an overall prevalence of 9.1%. The prevalence of cysts in GHD patients compared to ISS patients was not significant (13.5% vs. 5.7%, p=0.46). Mean cyst volume was greater in GHD patients than ISS patients (62.0 mm3vs. 29.4 mm3, p=0.01). POGO for GHD patients was significantly greater (p=0.003) than for ISS patients (15.3%±12.8 vs. 7.1%±8.0). Observers were blinded to patient groups.ConclusionsGHD patients had a significantly greater volume and POGO compared to ISS patients. This raises the question of whether cysts are implicated in the pathology of growth failure.

scholarly journals The Efficacy of Anastrozole and Growth Hormone Therapy on Adult Height in Six Adolescent Males with Growth Hormone Deficiency or Idiopathic Short Stature

2017 ◽  
Vol 2017 ◽  
pp. 1-6
Author(s):  
Serife Uysal ◽  
Juanita K. Hodax ◽  
Lisa Swartz Topor ◽  
Jose Bernardo Quintos
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Short Stature ◽  
Adult Height ◽  
Bone Age ◽  
Idiopathic Short Stature ◽  
Hormone Deficiency ◽  
Chronological Age ◽  
Gh Therapy ◽  
The Mean

Background. Data on adult height outcomes of the use of Anastrozole and Growth Hormone (GH) in pubertal males with Growth hormone deficiency (GHD) and Idiopathic short stature (ISS) are limited. Objective. We examined the effect of Anastrozole and GH therapy on near adult height (NAH) with pubertal males with GHD or ISS. Methods. Retrospective review of 419 charts from 2008 to 2015. The primary outcomes are NAH compared to mid-parental target height (MPTH) and predicted adult height (PAH). Results. We identified 23 patients (5 SGA/IUGR, 1 Noonan syndrome, 6 GHD, and 11 ISS). Six patients (4 GHD; 2 ISS) achieved NAH. Prior to Anastrozole treatment, the mean chronological age was 13.9±0.2 years (range 13.7–14.4), bone age was 13.6±0.6 years (range 12.5–14), mean height SDS was -1.5±0.5 (range −0.8 to −2.3), and mean PAH was 162.6±5.9 cm (range 153.5–168.6). MPTH was 173.6 cm ± 7 (range 161.8–181.6). Patients received Anastrozole for an average of 30.5 months (range 19–36 months). At NAH, the mean chronological age was 16.7±0.8 years (range 15.9–18.1 years) and height was 170±1.8 cm (range 168.5–173.4 cm). The mean height SDS improved to +0.81±0.6 (range +0.08 to +1.92, p=0.002). Net height gain was 7.3 cm compared to pretreatment PAH (p<0.01) and overall the mean adult height remained 3.5 cm below MPTH. Conclusion. Anastrozole and GH therapy can be effective in augmenting adult height without significant side effects. However, the long-term safety and efficacy of aromatase inhibitor use in pediatrics remain limited.

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