scholarly journals Short stature-advanced bone age-early-onset osteoarthritis syndrome

2020 ◽  
Author(s):  
Keyword(s):  
Short Stature ◽  
Early Onset ◽  
Bone Age

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 Clinical Characterization of Patients With Autosomal Dominant Short Stature due to Aggrecan Mutations

2016 ◽  
Vol 102 (2) ◽  
pp. 460-469 ◽  
Author(s):  
Alexandra Gkourogianni ◽  
Melissa Andrew ◽  
Leah Tyzinski ◽  
Melissa Crocker ◽  
Jessica Douglas ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Short Stature ◽  
Early Onset ◽  
Autosomal Dominant ◽  
Standard Deviation Score ◽  
Bone Age ◽  
Skeletal Maturation ◽  
Disc Disease ◽  
Phenotypic Spectrum ◽  
Median Height

Abstract Context: Heterozygous mutations in the aggrecan gene (ACAN) cause autosomal dominant short stature with accelerated skeletal maturation. Objective: We sought to characterize the phenotypic spectrum and response to growth-promoting therapies. Patients and Methods: One hundred three individuals (57 females, 46 males) from 20 families with autosomal dominant short stature and heterozygous ACAN mutations were identified and confirmed using whole-exome sequencing, targeted next-generation sequencing, and/or Sanger sequencing. Clinical information was collected from the medical records. Results: Identified ACAN variants showed perfect cosegregation with phenotype. Adult individuals had mildly disproportionate short stature [median height, −2.8 standard deviation score (SDS); range, −5.9 to −0.9] and a history of early growth cessation. The condition was frequently associated with early-onset osteoarthritis (12 families) and intervertebral disc disease (9 families). No apparent genotype–phenotype correlation was found between the type of ACAN mutation and the presence of joint complaints. Childhood height was less affected (median height, −2.0 SDS; range, −4.2 to −0.6). Most children with ACAN mutations had advanced bone age (bone age − chronologic age; median, +1.3 years; range, +0.0 to +3.7 years). Nineteen individuals had received growth hormone therapy with some evidence of increased growth velocity. Conclusions: Heterozygous ACAN mutations result in a phenotypic spectrum ranging from mild and proportionate short stature to a mild skeletal dysplasia with disproportionate short stature and brachydactyly. Many affected individuals developed early-onset osteoarthritis and degenerative disc disease, suggesting dysfunction of the articular cartilage and intervertebral disc cartilage. Additional studies are needed to determine the optimal treatment strategy for these patients.

scholarly journals Can exaggerated response to a GH provocative test identify patients with partial GH insensitivity syndrome?

2002 ◽  
pp. 319-323 ◽  
Author(s):  
Y Rakover ◽  
A Silbergeld ◽  
I Lavi ◽  
R Masalha ◽  
IB Shlomo
Keyword(s):  
Short Stature ◽  
Binding Protein ◽  
Standard Deviation Score ◽  
Bone Age ◽  
The Other ◽  
Provocative Test ◽  
Igf I ◽  
Parental Height ◽  
The Difference ◽  
Igfbp 3

OBJECTIVES: In the majority of children with short stature, the etiology is unknown. Mutations of the GH receptor (GHR) have been reported in a few children with apparent idiopathic short stature (ISS). These patients had low IGF-I, IGF-binding protein-3 (IGFBP-3) and GH-binding protein (GHBP), but a normal or exaggerated GH response to provocative stimuli, suggestive of partial GH insensitivity (GHI). We attempted to identify children with partial GHI syndrome, based on their response to GH provocative stimuli and other parameters of the GH-IGF-I axis. SUBJECTS AND METHODS: One hundred and sixty-four pre-pubertal children (97 boys, 67 girls) aged 7.2 (0.5-16.75) years were studied. All had short stature with height <3rd centile. The weight, bone age (BA) and body mass index (BMI) of the subjects, as well as the parents' heights and mid parental height (MPH) were assessed. Basal blood samples were taken for IGF-I, IGFBP-3 and GHBP. All subjects underwent a GH provocative test with either clonidine, arginine or insulin. The subjects were divided into three groups: (A) patients with peak GH concentration <18 mIU/l in two different provocative tests (GH deficiency - GHD, n=33); (B) patients with peak GH between 18.2 and 39.8 mIU/l (normal response, n=78); (C) patients with peak GH >40 mIU/l (exaggerated GH response, n=53). RESULTS: No significant differences were found in age, height (standard deviation score (SDS)), parental height (SDS) and the difference between chronological age and bone age (DeltaBA) between the groups. Patients with GHD were heavier (P=0.039) and had significantly higher BMI (SDS) (P=0.001) than the other groups. MPH (SDS) was lower in the group of exaggerated responders (P=0.04) compared with the other groups. No significant differences were found between the groups for the biochemical parameters when expressed nominally or in SDS, except for IGFBP-3 (SDS), which was lower in the GHD group (P=0.005). The GHBP levels were not lower in the group of exaggerated GH response to provocative stimuli. Height (SDS) correlated negatively with basal GH values in pooled data of all the subjects (r=-0.358, P<0.0001), in normal responders (r=-0.45, P<0.0001) and in the exaggerated responders (r=-0.341, P<0.0001), but not in the GHD group. CONCLUSION: Exaggerated GH response to provocative tests alone does not appear to be useful in identifying children with GHI.

scholarly journals Mutations of uncertain significance in heterozygous variants as a possible cause of severe short stature: a case report

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Nami Mohammadian Khonsari ◽  
Sahar Mohammad Poor Nami ◽  
Benyamin Hakak-Zargar ◽  
Tessa Voth
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Hormone Receptors ◽  
Bone Growth ◽  
Synergistic Effects ◽  
Signs And Symptoms ◽  
Bone Age ◽  
Pathogenic Mutation ◽  
Paracrine Factors ◽  
Severe Short Stature

Abstract Background Linear bone growth is achieved by the division of chondrocytes at the growth plate and is regulated by endocrine and paracrine factors such as growth hormone. Mutations that negatively affect chondrogenesis can be a contributor to short stature. One such mutation can occur in the ACAN gene, causing short stature and advanced bone age. Similarly, mutations in growth hormone receptors (GHR) can lead to Laron syndrome (LS), one of the several disorders that are collectively called growth hormone insensitivity syndrome (GHI). Another example is Floating-Harbor syndrome (FHS), a rare autosomal dominant due to mutations in the SRCAP gene that can also result in short stature. Case presentation We report the case of a 6-year-old female with concomitant mutations in the three genes mentioned above. The mutations reported here were found on genetic studies and are usually benign, causing a variant of undetermined significance. However, our patient’s phenotype could only be explained by the compounded effects of pathogenic mutations of these genes. Some of the same mutations were also found in the patient’s father and her paternal grandfather. Both also presented with short stature, though not to the same degree as our patient. While these mutations are often reported to be insignificant, they gave rise to severe short stature and a specific phenotype in the patient when presented together. We think that even though the GHI spectrum is inherited through an autosomal recessive pattern, the sum of these heterozygous mutations resulted in severe short stature despite the limited GHI seen in our patient, the father, and the grandfather, through a rare ACAN and SRCAP mutation that, to our knowledge, has not been previously reported as a pathogenic mutation in the literature. Conclusion We investigated the possible synergistic effects of these variations on exacerbation or masking of the signs and symptoms of GHI with the hope of providing a better understanding of these genes and their function through our rare case.

scholarly journals Turner Syndrome, Uncommonly Diagnosed Cause of Short Stature: Case Report and Review of Literature

2013 ◽  
Vol 33 (1) ◽  
pp. 74-76
Author(s):  
S Basnet ◽  
A Eleena ◽  
AK Sharma
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Turner Syndrome ◽  
Age Estimation ◽  
Bone Age ◽  
Review Of Literature ◽  
X Ray ◽  
Dysmorphic Features ◽  
The Past ◽  
Hormone Analysis

Many children are frequently brought to the paediatric clinic for evaluation of short stature. Evaluation for these children does not go beyond x-ray for bone age estimation and growth hormone analysis. Most of them are considered having constitutional or genetic cause for their short stature. However, shuttle dysmorphic features could be missed in many of them. Hence, many children might be having chromosomal anomaly as an underlying cause. We report a case of 40 months who had been evaluated several times in the past for pneumonia, otitis media and short stature is finally diagnosed to have Turner syndrome. DOI: http://dx.doi.org/10.3126/jnps.v33i1.8174 J Nepal Paediatr Soc. 2013;33(1):74-76

scholarly journals Idiopathic short stature due to novel heterozygous mutation of the aggrecan gene

2015 ◽  
Vol 28 (7-8) ◽  
Author(s):  
Jose Bernardo Quintos ◽  
Michael H. Guo ◽  
Andrew Dauber
Keyword(s):  
Short Stature ◽  
Adult Height ◽  
Frameshift Mutation ◽  
Index Case ◽  
Bone Age ◽  
Heterozygous Mutation ◽  
Maternal Grandfather ◽  
Whole Exome ◽  
Heterozygous Variant ◽  
History Of

AbstractRecently, whole exome sequencing identified heterozygous defects in the aggrecan (We report a novel frameshift mutation inWe present a 5 1/2-year-old male with a family history of short stature in three generations. The maternal grandfather stands 144.5 cm (Ht SDS –4.7), mother 147.7 cm (Ht SDS –2.6), and index case 99.2 cm (Ht SDS –2.7). Our prepubertal patient has significant bone age advancement (bone age 8 years at chronologic age 5 1/2 years) resulting in a poor predicted adult height of 142 cm (Ht SDS –5.1). DNA sequencing identified a novel heterozygous variant inMutations in the

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.

Familial X/Y Translocation Encompassing ARSE in Two Moroccan Siblings with Sensorineural Deafness

2017 ◽  
Vol 153 (2) ◽  
pp. 66-72
Author(s):  
Saadia Amasdl ◽  
Wiam Smaili ◽  
Abdelhafid Natiq ◽  
Amale Hassani ◽  
Aziza Sbiti ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Short Stature ◽  
X Chromosome ◽  
Chromosome Region ◽  
Sensorineural Deafness ◽  
Bone Age ◽  
Chondrodysplasia Punctata ◽  
Y Chromosomes ◽  
Contiguous Gene ◽  
Potential Evaluation

Unbalanced translocations involving X and Y chromosomes are rare and associated with a contiguous gene syndrome. The clinical phenotype is heterogeneous including mainly short stature, chondrodysplasia punctata, ichthyosis, hypogonadism, and intellectual disability. Here, we report 2 brothers with peculiar gestalt, short stature, and hearing loss, who harbor an X/Y translocation. Physical examination, brainstem acoustic potential evaluation, bone age, hormonal assessment, and X-ray investigations were performed. Because of their dysmorphic features, karyotyping, FISH, and aCGH were carried out. The probands had short stature, hypertelorism, midface hypoplasia, sensorineural hearing loss, normal intelligence as well as slight radial and ulnar bowing with brachytelephalangy. R-banding identified a derivative X chromosome with an abnormally expanded short arm. The mother was detected as a carrier of the same aberrant X chromosome. aCGH disclosed a 3.1-Mb distal deletion of chromosome region Xp22.33pter. This interval encompasses several genes, especially the short stature homeobox (SHOX) and arylsulfatase (ARSE) genes. The final karyotype of the probands was: 46,Y,der(X),t(X;Y)(p22;q12).ish der(X)(DXYS129-,DXYS153-)mat.arr[hg19] Xp22.33(61091_2689408)×1mat,Xp22.33(2701273_3258404)×0mat,Yq11.222q12 (21412851_59310245)×2. Herein, we describe a Moroccan family with a maternally inherited X/Y translocation and discuss the genotype-phenotype correlations according to the deleted genes.

DIFFERENCES IN BONE AGE READINGS BETWEEN PEDIATRIC ENDOCRINOLOGISTS AND RADIOLOGISTS

2020 ◽  
Vol 26 (3) ◽  
pp. 328-331 ◽  
Author(s):  
Kelsey B. Eitel ◽  
Erica A. Eugster
Keyword(s):  
Short Stature ◽  
Precocious Puberty ◽  
Retrospective Chart Review ◽  
Tanner Stage ◽  
Bone Age ◽  
X Rays ◽  
Clinical Variables ◽  
Greulich And Pyle ◽  
Pediatric Endocrinologist ◽  
Greulich And Pyle Method

Objective: Pediatric endocrinologists (PEs) have historically read their own bone age (BA) X-rays based on the belief that radiologists do not accurately interpret these tests. Whether there are significant differences in BA interpretations between these two groups has not been systematically explored. The objectives of the study were to compare BA readings performed by PEs and radiologists and determine whether clinical variables were associated with discrepancies in readings. Methods: A retrospective chart review of children presenting for initial evaluation of short stature (SS) or precocious puberty (PP) who had a BA X-ray completed was performed. Clinical variables analyzed included age, gender, ethnicity, Tanner stage, body mass index, reason for referral, radiologist location (Children's vs. outside hospital), and PE and radiologist BA readings using the Greulich and Pyle method. Results: Of 103 patients aged 9 ± 3.66 years, there was a discrepancy between the PE and radiologist readings on 70 images (68%). Discrepancy ranged from −1.5 to 3.5 years, with a mean of 4 ± 12 months. Patients referred for PP were more likely to have discrepant interpretations than those referred for SS (8.4 months vs. 0.8 months; P = .007). No differences were seen in interpretations between in-house radiologists and those at outside hospitals. Conclusion: Radiologists interpreted BAs differently than PEs in the majority of images. In patients referred for PP, BAs were interpreted as being older by radiologists than by PEs, perhaps due to bias from the reason for referral. Our results provide support for continued independent BA interpretations by PEs. Abbreviations: BA = bone age; GP = Greulich and Pyle; PE = pediatric endocrinologist; PP = precocious puberty; SS = short stature

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