scholarly journals SHOX deficiency in children with growth impairment: evaluation of known and new auxological and radiological indicators

2020 ◽  
Vol 46 (1) ◽  
Author(s):  
Silvia Vannelli ◽  
Maria Baffico ◽  
Raffaele Buganza ◽  
Francesca Verna ◽  
Giulia Vinci ◽  
...  
Keyword(s):  
Young Children ◽  
De Novo ◽  
Bone Age ◽  
Radiological Sign ◽  
Height Ratio ◽  
Shox Gene ◽  
X Ray ◽  
Growth Impairment ◽  
Sitting Height ◽  
Arm Span

Abstract Background The phenotypic features of SHOX deficiency (SHOX-D) are highly variable and can be very mild, especially in young children. The aim of this retrospective study was to evaluate auxological and radiological indicators that could be predictive of SHOX-D in children. Methods Molecular analysis of the SHOX gene was performed in 296 subjects with growth impairment or skeletal disproportion, without alternative diagnosis. Auxological variables and radiographs of the hand, wrist and forearm were evaluated. Results SHOX mutations (88% inherited, 12% de novo) were identified in 52 subjects. The most predictive auxological indicators of SHOX-D were an increased sitting height/height ratio and a decreased arm span/height ratio. The convexity of distal radial metaphysis at X-ray, not yet reported in literature, was also found to be predictive of SHOX-D. In young children, stratification of data by bone age also highlighted ulnar tilt, lucency of the ulnar border of the distal radius and enlarged radius as the radiological signs most related to SHOX-D . Conclusions In this study, the analysis of auxological and radiological indicators in SHOX-D children allowed to identify an additional early radiological sign and underlines the importance of family auxological evaluation.

scholarly journals Auxology Is a Valuable Instrument for the Clinical Diagnosis of SHOX Haploinsufficiency in School-Age Children with Unexplained Short Stature

2003 ◽  
Vol 88 (10) ◽  
pp. 4891-4896 ◽  
Author(s):  
Gerhard Binder ◽  
Michael B. Ranke ◽  
David D. Martin
Keyword(s):  
Short Stature ◽  
De Novo ◽  
Fragment Size ◽  
Mutation Screening ◽  
Idiopathic Short Stature ◽  
Paternal Allele ◽  
Leg Length ◽  
Sitting Height ◽  
Arm Span ◽  
Hand Radiography

Abstract SHOX (short stature homeobox-containing gene) mutations causing haploinsufficiency have been reported in some individuals with idiopathic short stature and in many patients with Leri-Weill-dyschondrosteosis. Around 80% of SHOX mutations are complete gene deletions, whereas diverse point mutations account for the rest. The aim of this study was to estimate the prevalence of SHOX mutations in children with idiopathic short stature and to give an unbiased characterization of the haploinsufficiency phenotype of such children. We recruited 140 children (61 girls), in our clinic, with idiopathic short stature, which was defined by the presence of normal IGF-I and free T4; a normal karyotype in females; the absence of endomysium antibodies, of chronic organic, psychological, or syndromatic disease; and by the lack of clear signs of any osteodysplasia. Height, arm span, and sitting height were recorded, and subischial leg length was calculated. Two highly polymorphic microsatellite markers located around the SHOX coding region (CA-SHOX repeat and DXYS233) were PCR-amplified with fluorescent primers and separated in an automatic sequencing machine. Analysis of parental DNA was performed in the probands who had only one fragment size of each of both markers. SHOX haploinsufficiency caused by a SHOX deletion was confirmed in three probands (2%), all females, who carried a de novo deletion through loss of the paternal allele. Their auxological data revealed a significant shortening of arms and legs in the presence of a low-normal sitting height, when compared with the other 137 children tested. Therefore, the extremities-trunk ratio (sum of leg length and arm span, divided by sitting height) for total height was significantly lower in the three SHOX haploinsufficient probands, in comparison with the whole group. This observation was confirmed with the auxological data of five additional patients (four females) previously diagnosed with SHOX haploinsufficiency; all but the youngest girl had height-adjusted extremities-trunk ratios more than 1 sd below the mean. All children with SHOX haploinsufficiency exhibited at least one characteristic radiological sign of Leri-Weill-dyschondrosteosis in their left-hand radiography, namely triangularization of the distal radial epiphysis, pyramidalization of the distal carpal row, or lucency of the distal ulnar border of the radius. Our observations suggest that it is rational to limit SHOX mutation screening to children with an extremities-trunk ratio less than 1.95 + 1/2 height (m) and to add a critical judgment of the hand radiography.

Anthropometric, biochemical and hormonal profiles of the partially admixed pygmoid group in Rampasasa (Flores, Indonesia)

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Aman Pulungan ◽  
Attika A. Andarie ◽  
Frida Soesanti ◽  
Muhammad Ramdhani Yassien ◽  
Christiaan de Bruin ◽  
...  
Keyword(s):  
Head Circumference ◽  
Standard Deviation Score ◽  
Bone Age ◽  
Skeletal Maturation ◽  
Delayed Puberty ◽  
Pubertal Stage ◽  
Sitting Height ◽  
Arm Span ◽  
Igf I ◽  
Igfbp 3

Abstract Objectives We performed a cross-sectional study on anthropometric and laboratory characteristics of inhabitants of Rampasasa (Flores, Indonesia). Adults were categorised according to ancestry into three groups: pygmoid (P/P, offspring of pygmoid parents, n=8), mixed pygmoid (P/N, offspring of pygmoid and non-pygmoid parents, n=12) and non-pygmoid (N/N, n=10). Children (n=28) were P/N. Methods Measurements included height, weight, sitting height, arm span, head circumference, haematological analysis and serum albumin, calcium, vitamin D, insulin-like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3). Pubertal stage and bone age was assessed in children. Anthropometric data were expressed as standard deviation score (SDS) for age. IGF-I, IGFBP-3 and IGF-I/IGFBP-3 ratio were expressed for age, bone age and pubertal stage. Results Mean height SDS showed a gradient from P/P (−4.0) via P/N (−3.2) to N/N (−2.3) (−3.4, −3.1 and −2.2 adjusted for age-associated shrinking). Sitting height and head circumference showed similar gradients. Serum IGF-I SDS was similar among groups (approximately −1 SDS). IGFBP-3 SDS tended toward a gradient from P/P (−1.9) via P/N (−1.5) to N/N (−1.1), but IGF-I/IGFBP-3 ratio was normal in all groups. In P/P and P/N, mean head circumference SDS was >2 SD greater than mean height SDS. Children showed a progressive growth failure and bone age delay, delayed female pubertal onset and an initial low serum IGF-I, normal IGFBP-3 and low IGF-I/IGFBP-3 ratio. Conclusions P/P showed proportionate short stature with relative macrocephaly and relatively low IGFBP-3; P/N presented an intermediate pattern. P/N children were progressively short, showed delayed skeletal maturation, delayed puberty in girls and low IGF-I and IGF-I/IGFBP-3.

scholarly journals A SHOX géndeletio előfordulása idiopáthiás alacsonynövésben. Multicentrikus tanulmány

2017 ◽  
Vol 158 (34) ◽  
pp. 1351-1356 ◽  
Author(s):  
Anna Dávid ◽  
Henriett Butz ◽  
Zita Halász ◽  
Dóra Török ◽  
Gábor Nyirő ◽  
...  
Keyword(s):  
Short Stature ◽  
Turner Syndrome ◽  
Normal Karyotype ◽  
Idiopathic Short Stature ◽  
Female Dominance ◽  
Shox Gene ◽  
Gene Deficiency ◽  
Sitting Height ◽  
Arm Span ◽  
Gene Alterations

Abstract: Introduction: The isolated haploinsufficiency of the SHOX gene is one of the most common cause of short stature determined by monogenic mutations. The heterozygous deviation of the gene can be detected in 2–15% of patients with idiopathic short stature (ISS), in 50–90% of patients with Leri-Weill dyschondrosteosis syndrome (LWS), and in almost 100% of patients with Turner syndrome. Aim: The aim of our study was to evaluate the frequency of SHOX gene haploinsufficiency in children with ISS, LWS and in patients having Turner syndrome phenotype (TF), but normal karyotype, and to identify the dysmorphic signs characteristic for SHOX gene deficiency. Method: A total of 144 patients were included in the study. Multiplex Ligation-dependent Probe Amplification (MLPA) method was used to identify the SHOX gene haploinsufficiency. The relationships between clinical data (axiological parameters, skeletal disorders, dysmorphic signs) and genotype were analyzed by statistical methods. Results: 11 (7.6%) of the 144 patients showed SHOX gene deficiency with female dominance (8/11, 81% female). The SHOX positive patients had a significantly higher BMI (in 5/11 vs. 20/133 cases, p<0.02) and presented more frequent dysmorphic signs (9/11vs 62/133, p = 0.02). Madelung deformity of the upper limbs was also significantly more frequent among the SHOX positive patients (4/11, i.e. 36%, vs. 14/133, i.e. 10%, p = 0.0066). There were no statistically significant differences between the mean age, mean height and auxological measurements (sitting height/height, arm span/height) between the two groups of patients. Conclusions: The occurrence of SHOX gene haploinsufficiency observed in our population corresponds to the literature data. In SHOX positive patients, in addition to short stature, the dysmorphic signs have a positive predictive value for SHOX gene alterations. However, the SHOX deletion detected in a patient with idiopathic short stature without dysmorphic signs suggest that SHOX deletion analysis can be recommended in patients with ISS. Orv Hetil. 2017; 158(34): 1351–1356.

Pubertal boy presenting with mild disproportionate short stature

2019 ◽  
pp. edpract-2019-317564
Author(s):  
Maria Chiara Pellegrin ◽  
Gianluca Tornese ◽  
Egidio Barbi
Keyword(s):  
Short Stature ◽  
Standard Deviation Score ◽  
Bone Age ◽  
Normal Weight ◽  
Hormone Deficiency ◽  
Growth Delay ◽  
List Type ◽  
Height Ratio ◽  
Pubertal Stage ◽  
Arm Span

A boy aged 12 years was referred with short stature. He was born at term, of adequate weight (10–25th centile) and length (10–25th centile), which settled to just below the third centile from 18 months of age, with a growth deceleration in the last 6 months (growth velocity −2.1 standard deviation score, according to Tanner charts). He was otherwise asymptomatic. His mother’s height was 155 cm, and father’s height 158 cm, and he was growing near his target height centile (−2.26 SDS, <3rd centile).On examination, his height was −2.22 SDS, with normal weight and body mass index (BMI). Pubertal stage corresponded to Tanner 2, with a testicular volume of 4 mL. His legs and forearms appeared shorter, with arm span/height ratio 0.93 (normal value >0.965) and sitting height/height ratio 0.56 (slightly above the normal upper value of 0.55). He resembled his father, whose wrists were abnormally curved (figure 1). The patient’s hand X-ray showed that bone age was similar to chronological age.Figure 1Disproportionate mesomelic short stature in the patient and in his father.QuestionsWhat is the most likely diagnosis?Constitutional growth delayGrowth hormone deficiencySHOX gene deficiencyIdiopathic short statureWhich diagnostic test should be considered?How should this patient be managed?Answers can be found on page 2.

scholarly journals Sitting height, sitting height/height ratio, arm span and arm span-height difference of healthy adolescents in Surakarta, Indonesia

2018 ◽  
Vol 58 (3) ◽  
pp. 138-45
Author(s):  
Annang Giri Moelyo ◽  
Lucky Yogasatria ◽  
Yusak Aditya Setyawan ◽  
Evi Rokhayati
Keyword(s):  
Reference Data ◽  
Female Adolescents ◽  
Height Ratio ◽  
Height Difference ◽  
Male And Female ◽  
Sitting Height ◽  
Arm Span ◽  
Significant Difference ◽  
History Of ◽  
The Mean

Background Sitting height, sitting height/height ratio (SHR), arm span, and arm span-height difference (AHD) are indices to diagnose conditions of disproportion. Reference data on sitting height, SHR, arm span, and AHD for Indonesian children are limited. Objective To compile reference data on sitting height, SHR, arm span, and AHD in Indonesian adolescents, and to compare these indices for boys and girls at various ages. Methods A population-based survey was conducted from August 2016 to November 2017 in three high schools in Surakarta, Central Java, Indonesia. A convenience sampling method was employed to recruit healthy adolescents without history of chronic disease, history of physical trauma, and/or physical disabilities. All subjects underwent anthropometric measurements (height, weight, sitting height, and arm span), and their ethnic origins were noted. The lambda-mu-sigma (LMS) method was used for reference construction. Results Of 639 subjects, 42% were male. Body mass index (BMI) values were similar between males and females. Mean height, weight, sitting height, and arm span of males were greater than those of females. The mean male and female SHRs were 51.1 (SD 1.6) % and 51.0 (SD 1.6) %, respectively (P=0.36), while the mean AHDs were 4.2 (SD 4.5) cm and 3.4 (SD 4.1) cm, respectively (P=0.02). The formula to estimate height based on arm span in males was [height = (0.78 x arm span) + 32.14] in cm. The formula in females was [height = (0.66 x arm span) + 50.59] in cm. Conclusion There was no significant difference in SHR between male and female adolescents. However, males haVE significantly larger mean AHD than females. We provide references on sitting height, SHR, arm span, and AHD in male and female adolescents.

Bone age determination using dual-energy X-ray absorptiometry

2017 ◽  
Author(s):  
Khalaf Alshamrani ◽  
Amaka Offiah ◽  
Elzene kruger
Keyword(s):  
Age Determination ◽  
Bone Age ◽  
Dual Energy ◽  
X Ray

scholarly journals Intelligent Bone Age Assessment: An Automated System to Detect a Bone Growth Problem Using Convolutional Neural Networks with Attention Mechanism

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 765
Author(s):  
Mohd Asyraf Zulkifley ◽  
Nur Ayuni Mohamed ◽  
Siti Raihanah Abdani ◽  
Nor Azwan Mohamed Kamari ◽  
Asraf Mohamed Moubark ◽  
...  
Keyword(s):  
Bone Growth ◽  
Bone Age ◽  
Attention Mechanism ◽  
Assessment System ◽  
Dominant Hand ◽  
Age Assessment ◽  
Image Normalization ◽  
X Ray ◽  
Bone Age Assessment ◽  
Skeletal Bone

Skeletal bone age assessment using X-ray images is a standard clinical procedure to detect any anomaly in bone growth among kids and babies. The assessed bone age indicates the actual level of growth, whereby a large discrepancy between the assessed and chronological age might point to a growth disorder. Hence, skeletal bone age assessment is used to screen the possibility of growth abnormalities, genetic problems, and endocrine disorders. Usually, the manual screening is assessed through X-ray images of the non-dominant hand using the Greulich–Pyle (GP) or Tanner–Whitehouse (TW) approach. The GP uses a standard hand atlas, which will be the reference point to predict the bone age of a patient, while the TW uses a scoring mechanism to assess the bone age using several regions of interest information. However, both approaches are heavily dependent on individual domain knowledge and expertise, which is prone to high bias in inter and intra-observer results. Hence, an automated bone age assessment system, which is referred to as Attention-Xception Network (AXNet) is proposed to automatically predict the bone age accurately. The proposed AXNet consists of two parts, which are image normalization and bone age regression modules. The image normalization module will transform each X-ray image into a standardized form so that the regressor network can be trained using better input images. This module will first extract the hand region from the background, which is then rotated to an upright position using the angle calculated from the four key-points of interest. Then, the masked and rotated hand image will be aligned such that it will be positioned in the middle of the image. Both of the masked and rotated images will be obtained through existing state-of-the-art deep learning methods. The last module will then predict the bone age through the Attention-Xception network that incorporates multiple layers of spatial-attention mechanism to emphasize the important features for more accurate bone age prediction. From the experimental results, the proposed AXNet achieves the lowest mean absolute error and mean squared error of 7.699 months and 108.869 months2, respectively. Therefore, the proposed AXNet has demonstrated its potential for practical clinical use with an error of less than one year to assist the experts or radiologists in evaluating the bone age objectively.

scholarly journals Optimization in S-SAD phasing - difference between solved and unsolved structure

2014 ◽  
Vol 70 (a1) ◽  
pp. C613-C613
Author(s):  
Jan Stránský ◽  
Tomáš Kovaľ ◽  
Lars Østergaard ◽  
Jarmila Dušková ◽  
Tereza Skálová ◽  
...  
Keyword(s):  
Data Processing ◽  
De Novo ◽  
Protein Structures ◽  
X Ray Diffraction ◽  
X Ray ◽  
Structure Solution ◽  
Sad Phasing ◽  
Optimal Values ◽  
Grant Agency ◽  
Intensity Reading

Development of X-ray diffraction technologies have made de novo phasing of protein structures by single-wavelength anomalous dispersion by sulphur (S-SAD) more common. As anomalous differences in the sulphur atomic factors are in the order of errors of measurement, careful intensity reading and data processing are crucial. S-SAD was used for de novo phasing of a small 12 kDa protein with 4 sulphur atoms per molecule at 2.3 Å, where the data did not enable a straightforward structure solution. Data processing was performed using XDS [1] and scaling using XSCALE. The sulphur substructure was determined by SHELXD [2] and phases were obtained from SHELXE [2]. Both algorithms strongly depend on input parameters and default values did not lead to the correct phases. Therefore a systematic search of optimal values of several parameters was used to find a solution. This method helped to confirm sulphur substructure and to differentiate the handedness of the solutions. Moreover, a script for comfortable conversion of SHELX outputs to MTZ format was developed, using programmes included in the CCP4 package [3]. The previously unsolvable protein structure was successfully resolved with the described procedure. This work was supported by the Grant Agency of the Czech Technical University in Prague, (SGS13/219/OHK4/3T/14), the Czech Science Foundation (P302/11/0855), project BIOCEV CZ.1.05/1.1.00/02.0109 from the ERDF.

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