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 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 MON-254 Sympromic Hypogonadism: Co- Existence of Morsier and Klinefelter Syndromes

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Fabiola romero ◽  
Sady Arzamendia ◽  
Dahiana Ferreira ◽  
Claudia Neves de Souza ◽  
Helen Lopez ◽  
...  
Keyword(s):  
Klinefelter Syndrome ◽  
External Genitalia ◽  
Psychomotor Retardation ◽  
Septum Pellucidum ◽  
Lower Limbs ◽  
Hormone Deficiency ◽  
Tall Stature ◽  
Male Hypogonadism ◽  
Optic Chiasma ◽  
First Case

Abstract INTRODUCTION: Morsier Syndrome is a rare congenital malformation, characterized by hypoplasia / aplasia of the septum pellucidum and hypoplasia / aplasia of the optic nerves, in addition to pituitary and hypothalamic hormonal deficiencies. Klinefelter Syndrome is a sexual chromosomal genetic alteration, a frequent cause of male hypogonadism, The association of Morsier syndrome and Klinefelter is described below. CLINICAL CASE We report he case of a 12 year-old boy with psychomotor retardation and nystagumsho presented at 14 months of age with growth hormone deficiency (low weight and height,) and diabetes insipuidus with hypernatremia of of 159 mEq and low urinary density (less than 1,005). MRI showed an absence of septum pellucidum, thick right frontal cortical dysplasia with asymmetric appearance of the grooves, small optic chiasma, hypoplastic pitutary gland (3 mm height), compatible with Morsier syndrome. The physical examination draws attention to tall stature, and long lower limbs, facies with prominent forehead and hypertelorism, gynecomastia and small external genitalia for age. Hormonal evaluation revealed hypergonadotropic hypogonadism with a 47 XXY karyoteype suggeting Klinefelter syndrome. CONCLUSION: We report the first case of Morsier syndrome, associated to Klinefelter syndrome. Both syndromes may present with hypogonadism. However, the diagnosis of klinefelter syndrome was made based on the phenotypic characteristics of this patient including hyeprgonadotroic hypogonadism and abnormal karyotype analysis.

scholarly journals Genetics of Growth Disorders—Which Patients Require Genetic Testing?

2019 ◽  
Vol 10 ◽  
Author(s):  
Jesús Argente ◽  
Katrina Tatton-Brown ◽  
Dagmar Lehwalder ◽  
Roland Pfäffle
Keyword(s):  
Genetic Testing ◽  
Growth Disorders

scholarly journals Growth and Pubertal Development in Elite Female Rhythmic Gymnasts

1999 ◽  
Vol 84 (12) ◽  
pp. 4525-4530 ◽  
Author(s):  
N. Georgopoulos ◽  
K. Markou ◽  
A. Theodoropoulou ◽  
P. Paraskevopoulou ◽  
L. Varaki ◽  
...  
Keyword(s):  
Body Fat ◽  
Adult Height ◽  
Pubertal Development ◽  
Optimal Growth ◽  
Bone Age ◽  
Skeletal Maturation ◽  
Chronological Age ◽  
Average Height ◽  
Limited Information ◽  
Rhythmic Gymnasts

Optimal growth depends upon both environmental and genetic factors. Among environmental factors that could alter growth and sexual maturation are stress and intensive physical training. The influence of these factors has been documented in a variety of sports, but there is limited information on rhythmic gymnasts, who have entirely different training and performance requirements. The study was conducted during the 13th European Championships in Patras, Greece, and included 255 female rhythmic gymnasts, aged 11–23 yr. The study included measurement of height and weight, assessment of breast and pubic hair development, estimation of body fat and skeletal maturation, and registration of menarcheal age and parental height. Gymnasts were taller than average height for age, with mean height above and mean weight below the 50th percentile. Actual height sd score was positively correlated to weight sd score (P < 0.001), number of competitions (P = 0.01), and body mass index (BMI; P < 0.001). Predicted adult height sd score was positively correlated to weight sd score (P < 0.001) and negatively to body fat (P = 0.004). There was a delay in skeletal maturation of 1.3 yr (P < 0.001). Pubertal development was following bone age rather than chronological age. The mean age of menarche was significantly delayed from that of their mothers and sisters (P = 0.008 and P = 0.05, respectively), was positively correlated to the intensity of training and to the difference between chronological age and bone age (P < 0.001 and P = 0.002, respectively), and was negatively correlated to body fat (P < 0.001). In the elite female rhythmic gymnasts, psychological and somatic efforts have profound effects on growth and sexual development. Despite these aberrations, adult height is not expected to be affected.

Precocious Puberty

2006 ◽  
Vol 00 (02) ◽  
Author(s):  
Paul B Kaplowitz
Keyword(s):  
Precocious Puberty ◽  
Linear Growth ◽  
Pubertal Development ◽  
Black Girls ◽  
Pubic Hair ◽  
Growth Spurt ◽  
Tall Stature ◽  
Early Puberty ◽  
Bone Maturation ◽  
Early Appearance

Precocious puberty refers to the appearance of physical and hormonal signs of pubertal development at an earlier age than is considered normal.Although traditionally, any signs of puberty in girls prior to age eight years have been considered abnormal, recent studies indicate that signs of early puberty (breasts and pubic hair) are often present in girls (particularly black girls) between ages 6–8 years.The early growth spurt initially can cause tall stature, but rapid bone maturation can cause linear growth to cease too early and result in short adult stature.The early appearance of breasts or menses in girls and increased libido in boys can cause emotional distress for some children.

Long-term follow-up of a child with Klinefelter syndrome and achondroplasia from infancy to 16 years

2017 ◽  
Vol 30 (7) ◽  
Author(s):  
Jessica D. Arditi ◽  
Loretta Thomaidis ◽  
Helen Frysira ◽  
Artemis Doulgeraki ◽  
George P. Chrousos ◽  
...  
Keyword(s):  
Sex Chromosome ◽  
De Novo ◽  
Klinefelter Syndrome ◽  
Pubertal Development ◽  
Pediatric Endocrinology ◽  
Case Presentation ◽  
Long Term Follow Up ◽  
Chromosome Disorder

AbstractBackground:Achondroplasia (ACH), an autosomal dominant skeletal dysplasia, occurs in approximately 1:20,000 births. On the other hand, 47,XXY aneuploidy (Klinefelter syndrome [KS]) is the most common sex chromosome disorder, with a prevalence of approximately 1:600 males. To the best of our knowledge, only five cases of patients presenting both ACH and KS have been reported to date in the international literature. However, none of these cases has been longitudinally followed during the entire childhood.Case presentation:We report a male patient with ACH and KS, diagnosed in early infancy because of his typical phenotype of ACH. The diagnosis was confirmed by molecular analysis revealing a de novo heterozygous 1138 G-to-A mutation of theConclusions:This is the first reported case with both conditions that was diagnosed in infancy and was longitudinally followed by a pediatric endocrinology team regularly, from infancy to late adolescence. With a typical phenotype of ACH, it is striking and noteworthy that he did not develop the classical endocrine complications of a child with KS, neither did he necessitate testosterone supplementation during his pubertal development, due to his normal virilization and testosterone levels.

Prepubertal Growth and Skeletal Maturation in Children With Sickle Cell Disease

PEDIATRICS ◽  
1986 ◽  
Vol 78 (1) ◽  
pp. 124-132
Author(s):  
Michael C. G. Stevens ◽  
Gillian H. Maude ◽  
Lena Cupidore ◽  
Helen Jackson ◽  
Richard J. Hayes ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Skeletal Maturity ◽  
Pubertal Development ◽  
Bone Age ◽  
Skeletal Maturation ◽  
Similar Data ◽  
Cell Disease ◽  
Normal Children ◽  
Normal Mean ◽  
Benign Nature

In a longitudinal study of 298 children with homozygous sickle cell (SS) disease and 157 children with hemoglobin SC disease, between birth and 9 years of age, observations of weight and height were made. These were compared with similar data derived from an age- and sex-matched group of 231 children with a normal hemoglobin (AA) genotype. Growth in children with SC disease was not significantly different from that in normal children, but children with SS disease had statistically significant, and progressive, deficits in both weight and height before 2 years of age. The average deficit approached 1 SD below the normal mean for age by 9 years. Observations of skeletal maturity, based on radiologic assessment of bone age at the wrist, were made on a proportion of these children at 5 and 8 years of age. Children with SS disease were significantly retarded at 8 years but not 5 years, which is consistent with increasing deficit in height. These observations confirm the early impact of SS disease on physical development and provide standards from which clinical expectations of growth may be derived. The relevance of these findings and their relationship to the characteristic delay in pubertal development is discussed together with a review of possible etiologic factors. The benign nature of SC disease is endorsed by the absence of an effect on growth in the prepubertal child.

scholarly journals Serum Insulin-Like Factor 3 Levels during Puberty in Healthy Boys and Boys with Klinefelter Syndrome

2006 ◽  
Vol 91 (11) ◽  
pp. 4705-4708 ◽  
Author(s):  
Anne M. Wikström ◽  
Katrine Bay ◽  
Matti Hero ◽  
Anna-Maria Andersson ◽  
Leo Dunkel
Keyword(s):  
Aromatase Inhibitor ◽  
Leydig Cell ◽  
Klinefelter Syndrome ◽  
Pubertal Development ◽  
Bone Age ◽  
University Hospital ◽  
Initial Increase ◽  
Prospective Clinical Study ◽  
Testosterone Levels ◽  
Cell Dysfunction

Abstract Context: Levels of the Leydig cell-specific hormone insulin-like factor 3 (INSL3) are incompletely characterized in boys during pubertal development. Objective: The objective of the study was to characterize changes in INSL3 levels during spontaneous puberty in healthy boys, boys with aromatase inhibitor-induced hypergonadotropic hyperandrogenism, and boys with Leydig cell dysfunction. Design: This was a prospective clinical study. Setting: The study was conducted at a university hospital pediatric endocrinology outpatient clinic. Patients: Patients included 30 healthy boys with idiopathic short stature (ISS) aged 9.0–14.5 yr and 14 boys with Klinefelter syndrome (KS) aged 10–13.9 yr. Intervention: In ISS boys, intervention included aromatase inhibitor letrozole or placebo for 24 months. Main Outcome Measures: Serum INSL3 levels in relation to bone age, Tanner pubertal stages, and LH and testosterone levels were measured. Results: Onset of puberty was associated with a significant increase in INSL3 levels from 0.06 ± 0.01 ng/ml at Tanner G1 to 0.32 ± 0.16 ng/ml at G2 (P < 0.0001). Adult INSL3 levels (≥0.55 ng/ml) were attained at bone age 13–14 yr. ISS boys with letrozole-induced hypergonadotropic hyperandrogenism had, after 12 months of therapy, higher INSL3 levels than did placebo treated (0.85 ± 0.54 vs. 0.26 ± 0.17 ng/ml, P < 0.01). In KS boys during spontaneous puberty, after an initial increase similar to that in healthy boys, INSL3 concentrations leveled off despite hyperstimulation by LH. Positive correlations occurred between serum INSL3 and LH and between INSL3 and testosterone levels in all three groups (P < 0.0001). Conclusions: In boys, the Leydig cell-specific hormone INSL3 may serve as a new marker for onset and progression of puberty. Pubertal increase in INSL3 levels seems to depend on LH. In KS subjects, INSL3 concentrations indicate Leydig cell dysfunction from midpuberty onward.

scholarly journals Unique plasma metabolite signature for adolescents with Klinefelter syndrome reveals altered fatty acid metabolism

2021 ◽  
Author(s):  
Shanlee Davis ◽  
Rhianna Urban ◽  
Angelo D'Alessandro ◽  
Julie A Reisz ◽  
Christine L Chan ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Molecular Mechanisms ◽  
Klinefelter Syndrome ◽  
Pubertal Development ◽  
Saturated Fatty Acids ◽  
Adolescent Males ◽  
Enrichment Ratio ◽  
Plasma Metabolites ◽  
Pubertal Stage ◽  
Plasma Metabolome

Conditions related to cardiometabolic disease, including metabolic syndrome and type 2 diabetes, are common among men with Klinefelter syndrome (KS). The molecular mechanisms underlying this aberrant metabolism in KS are largely unknown, although there is an assumption that chronic testosterone deficiency plays a role. This cross-sectional study compared plasma metabolites in 31 pubertal adolescent males with KS to 32 controls of similar age (14 ± 2 yrs), pubertal stage, and body mass index z-score (0.1 ± 1.2), and then between testosterone treated (n=16) and untreated males with KS. The plasma metabolome in males with KS was distinctly different from controls, with 22% of measured metabolites having a differential abundance and seven metabolites nearly completely separating KS from controls (AUC>0.9, p<0.0001). Multiple saturated free fatty acids were higher in KS while mono- and polyunsaturated fatty acids were lower, and the top significantly enriched pathway was mitochondrial β-oxidation of long-chain saturated fatty acids (enrichment ratio 16, p<0.0001). In contrast, there were no observed differences in metabolite concentrations between testosterone-treated and untreated individuals with KS. In conclusion, the plasma metabolome profile in adolescent males with KS is distinctly different from males without KS independent of age, obesity, pubertal development, or testosterone treatment status, and is suggestive of differences in mitochondrial β-oxidation.

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