scholarly journals Bilateral coxa vara and tibia vara associated with severe short stature in a girl manifesting a constellation of bone lesions with exclusive involvement of the lower limbs

2018 ◽  
Vol 6 (3) ◽  
pp. 63-69
Author(s):  
Ali Al Kaissi ◽  
Franz Grill ◽  
Rudolf Ganger ◽  
Susanne Gerit Kircher
Keyword(s):  
Short Stature ◽  
Skeletal Dysplasia ◽  
Lower Limbs ◽  
Bone Lesions ◽  
Coxa Vara ◽  
Tibia Vara ◽  
Osteolytic Lesions ◽  
Fibrocartilaginous Dysplasia ◽  
Medial Cortex ◽  
Severe Short Stature

In most instances, a toddler is seen with unilateral varus of the tibia, usually the deformity appearing slightly more distal than the knee joint. Radiographs of the focal fibrocartilaginous dysplasia show a characteristic abrupt varus at the metaphyseal — diaphyseal junction of the tibia. Cortical sclerosis is in and around the area of the abrupt varus on the medial cortex. A radiolucency may appear just proximal to the area of cortical sclerosis. The aetiology of such defects and the pathogenesis of the deformity are mostly unknown. Many of the associated factors suggest that the condition at least partly results from a mechanical overload of the medioproximal tibial physis. The evaluation of a child with suspected pathologic tibia vara begins with a thorough history. A complete birth and developmental history should include the age at which the child begun walking. The medical history should identify any renal disease, endocrinopathies, or known skeletal dysplasia. The physical examination also should include the child’s overall lower extremity alignment and symmetry, hip and knee motion, ligamentous hyperlaxity, and tibial torsion. We describe on a 17 year-old-girl who manifests severe short stature associated with multiple orthopaedic abnormalities, namely, bilateral coxa vara and tibia vara. Radiographic documentation showed bilateral and symmetrical involvement of the lower limbs with the extensive form of fibrocartilaginous dysplasia, osteoporosis, and osteolytic lesions. The constellation of the malformation complex of osteolytic lesions, fibrocartilaginous changes and the polycystic like fibromas are not consistent to any previously published reports of fibrocartilaginous dysplasia. To the best of our knowledge, it seems that fibrocartilaginous changes are part of a novel type of skeletal dysplasia.

scholarly journals Autosomal recessive chondrodysplasia with severe short stature caused by a biallelic COL10A1 variant

2017 ◽  
Vol 55 (6) ◽  
pp. 403-407 ◽  
Author(s):  
Noor ul Ain ◽  
Outi Makitie ◽  
Sadaf Naz
Keyword(s):  
Short Stature ◽  
Skeletal Dysplasia ◽  
In Silico ◽  
Autosomal Recessive ◽  
Limb Deformity ◽  
Mild Phenotype ◽  
Whole Exome ◽  
New Type ◽  
Severe Short Stature ◽  
Amino Acid Conservation

BackgroundHeterozygous mutations in COL10A1 underlie metaphyseal chondrodysplasia, Schmid type (MCDS), an autosomal dominant skeletal dysplasia.ObjectiveTo identify the causative variant in a large consanguineous Pakistani family with severe skeletal dysplasia and marked lower limb deformity.MethodsWhole exome sequencing was completed followed by Sanger sequencing to verify segregation of the identified variants. In silico variant pathogenicity predictions and amino acid conservation analyses were performed.ResultsA homozygous c.133 C>T (p.Pro45Ser) variant was identified in COL10A1 in all six severely affected individuals (adult heights 119–130 cm, mean ~−6.33 SD). The individuals heterozygous for the variant had mild phenotype of short stature (adult heights 140–162 cm, mean ~−2.15 SD) but no apparent skeletal deformities. The variant was predicted to be pathogenic by in silico prediction tools and was absent from public databases and hundred control chromosomes. Pro45 is conserved in orthologues and is located in the non-collagenous 2 domain of COL10A1, variants of which have never been associated with skeletal dysplasia.ConclusionsThis first report of individuals with a homozygous variant in COL10A1 defines a new type of autosomal recessive skeletal dysplasia. The observations in COL10A1 variant carriers suggest a phenotypic overlap between the mildest forms of MCDS and idiopathic short stature.

scholarly journals Pseudoachondroplasia: Report on a South African family

2013 ◽  
Vol 17 (2) ◽  
pp. 65-67 ◽  
Author(s):  
Shahida Moosa ◽  
Gen Nishimura
Keyword(s):  
Short Stature ◽  
South African ◽  
Skeletal Dysplasia ◽  
Autosomal Dominant ◽  
Lower Limbs ◽  
Normal Length ◽  
Radiographic Features ◽  
Radiological Features

Pseudoachondroplasia is an autosomal dominant skeletal dysplasia that results in disproportionately short stature, severe brachydactyly with strikingly lax small joints, malalignments of the lower limbs, and characteristic radiological features. Although named ‘false achondroplasia’, the entity is a distinct condition, in which affected individuals are born with normal length and have a normal facies, but is often only recognised after the age of 2 years, when the disproportion and waddling gait become evident. We report on an affected South African father and daughter, and highlight their clinical and radiographic features.

scholarly journals Leri-Weill Dyschondrosteosis Syndrome: Analysis via 3DCT Scan

Medicines ◽  
2019 ◽  
Vol 6 (2) ◽  
pp. 60
Author(s):  
Ali Al Kaissi ◽  
Mohammad Shboul ◽  
Vladimir Kenis ◽  
Franz Grill ◽  
Rudolf Ganger ◽  
...  
Keyword(s):  
3D Reconstruction ◽  
Ct Scan ◽  
Short Stature ◽  
Skeletal Dysplasia ◽  
Lower Limbs ◽  
Partial Closure ◽  
Female Patients ◽  
Coxa Valga ◽  
Syndrome Analysis

Background: Leri-Weill dyschondrosteosis (LWD) is a pseudoautosomal form of skeletal dysplasia, characterized by abnormal craniofacial phenotype, short stature, and mesomelia of the upper and lower limbs. Methods: We describe two female patients with LWD. Their prime clinical complaints were severe bouts of migraine and antalgic gait. Results: Interestingly, via a 3D reconstruction CT scan we encountered several major anomalies. Notable features of craniosynostosis through premature fusion of the squamosal sutures and partial closure of the coronal sutures were the reason behind the development of abnormal craniofacial contour. A 3D reconstruction CT scan showed apparent bulging of the clavarium through the partially synostosed coronal and totally synostosed squamosal sutures. Additional deformities include deficient number of ribs (10 ribs on both sides), defective ossification of the ischium and dysplasia of the iliac-ischial junction, and coxa valga have been noted. Conclusions: The constellation of observed deformities can be considered as a novel features associated with LWD.

scholarly journals Osteoglophonic Dysplasia: Phenotypic and Radiological Clues

2017 ◽  
Vol 06 (04) ◽  
pp. 247-251 ◽  
Author(s):  
Shwetha Kuthiroly ◽  
Dhanya Yesodharan ◽  
Aneesh Ghosh ◽  
Kenneth White ◽  
Sheela Nampoothiri
Keyword(s):  
Short Stature ◽  
Skeletal Dysplasia ◽  
Autosomal Dominant ◽  
Bone Age ◽  
Dominant Mode ◽  
Bone Lesions ◽  
Activating Mutations ◽  
Radiological Features ◽  
Proven Case ◽  
Mode Of Inheritance

AbstractOsteoglophonic dysplasia (OD) is an extremely rare, skeletal dysplasia with an autosomal dominant mode of inheritance. Rhizomelic dwarfism, craniosynostosis, impacted teeth, hypodontia or anodontia, and multiple nonossifying bone lesions are the salient features of this condition. We report a 14-year-old girl with clinical and radiological features consistent with OD. She presented with disproportionate short stature, craniosynostosis, a prominent supraorbital ridge, delayed teeth eruption, hypodontia, and multiple nonossifying bone lesions in the femur, tibia, and fibula. She had hypophosphatemia, which is a known association in this dysplasia. She also had advanced bone age, which is an unreported feature of this dysplasia. This condition is caused by activating mutations in FGFR1. A missense mutation was detected in the FGFR1, NM_001174067 (FGFR1_v001):c.1115G > A [p.(Cys372Tyr)] confirming the diagnosis; this is the first mutation-proven case to be reported from India.

scholarly journals Heterozygous NPR2 Mutation in Two Family Members with Short Stature and Skeletal Dysplasia

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Marianne Jacob ◽  
Surabhi Menon ◽  
Christina Botti ◽  
Ian Marshall
Keyword(s):  
Short Stature ◽  
Natriuretic Peptide ◽  
Skeletal Dysplasia ◽  
Endochondral Ossification ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Loss Of Function ◽  
Peptide Receptor ◽  
Radiological Features ◽  
Severe Short Stature

Endochondral ossification at the level of the growth plate, an essential process involved in longitudinal growth, is regulated by hormonal and local factors including C-type natriuretic peptide and its receptor, natriuretic peptide receptor B. Biallelic loss-of-function mutations in the NPR2 gene, which encodes this receptor, cause acromesomelic dysplasia, Maroteaux type (AMDM), a skeletal dysplasia characterized by severe short stature and disproportionate shortening of limbs. Heterozygous NPR2 mutations have been reported in patients previously classified with idiopathic short stature (ISS). We report the presentation of a 7-year-old girl and her mother with short stature, both of whom were identified with the same NPR2 mutation, and who demonstrated clinical and radiological features consistent with a skeletal dysplasia. We also report the patient’s response to recombinant human growth hormone (rhGH) over a 2-year period. We encourage clinicians who evaluate children with ISS to consider genetic testing, particularly when the presentation is associated with features suggestive of a skeletal dysplasia.

scholarly journals Clinical profiles and genetic spectra of 814 Chinese children with short stature

2021 ◽  
Author(s):  
Xin Li ◽  
Ruen Yao ◽  
Guoying Chang ◽  
Qun Li ◽  
Cui Song ◽  
...  
Keyword(s):  
Short Stature ◽  
Skeletal Dysplasia ◽  
Large Scale ◽  
Chromosomal Abnormalities ◽  
Copy Number Variations ◽  
Facial Dysmorphism ◽  
Diagnostic Efficiency ◽  
Pathogenic Genes ◽  
Diagnostic Characteristics ◽  
Severe Short Stature

Abstract Context Data of and studies based on exome sequencing for the genetic evaluation of short stature are limited, and more large-scale studies are warranted. Some factors increase the likelihood of a monogenic cause of short stature, including skeletal dysplasia, severe short stature, and small for gestational age (SGA) without catch-up growth. However, whether these factors can serve as predictors of molecular diagnosis remains unknown. Objectives We aimed to explore the diagnostic efficiency of the associated risk factors and their exome sequences for screening. Design, Settings, and Patients We defined and applied factors that increased the likelihood of monogenic causes of short stature in diagnostic genetic tests based on next-generation sequencing (NGS) in 814 patients with short stature and at least one other factor. Results Pathogenic/likely pathogenic (P/LP) variants in genes, copy number variations (CNVs), and chromosomal abnormalities were identified in 361 patients. We found P/LP variants among 111 genes, and RASopathies comprised the most important etiology. Short stature combined with other phenotypes significantly increased the likelihood of monogenic cause, including skeletal dysplasia, facial dysmorphism, and intellectual disability, compared with simple severe short stature (<–3 standard deviation scores). We report novel candidate pathogenic genes, KMT2C for unequivocal growth hormone insensitivity and GATA6 for SGA. Conclusions Our study identified the diagnostic characteristics of NGS in short stature with different risk factor. Our study provides novel insights into the current understanding of the etiology of short stature in patients with different phenotypes.

Growth hormone therapy in a child with severe short stature due to Miller-McKusick-Malvaux (3M) syndrome-2

2019 ◽  
Author(s):  
Sumudu Seneviratne ◽  
Deepthi de Silva ◽  
Emily Cottrell ◽  
Piumi Kuruppu ◽  
KSH de Silva ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Therapy ◽  
Short Stature ◽  
Growth Hormone Therapy ◽  
Severe Short Stature

scholarly journals AB0781 ONE, NONE, MANY: REFLECTIONS ON A RARE CASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1416.2-1416
Author(s):  
G. Sandri ◽  
L. Belletti ◽  
M. Cavedoni ◽  
C. Galluzzo ◽  
S. Bruni ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Autoimmune Diseases ◽  
Short Stature ◽  
Rare Diseases ◽  
Bone Development ◽  
Therapeutic Interventions ◽  
Cardiac Conduction ◽  
Bone Lesions ◽  
The European Union ◽  
Early Puberty

Background:Rare diseases are all those diseases that present, in the European Union, a prevalence of less than 5 cases per 10,000 people. The number of rare diseases is estimated at roughly 7,000 but there are also longstanding medical conditions that elude diagnosis and could be identified as rare.Objectives:Demonstrate the importance of international research in orphan diseases.Methods:We report a case of 44 y/o female patient who arrived to our observation in 2006. Short stature, early puberty, ligament laxity, BMI <17. From the age of 29: recurrent diarrhea, pain in the spine, osteolytic lesions in spine and endosteal thickening in long bones, muscle contractures, strength deficit, muscular hypotrophy and hypotonia, cardiac conduction and blood pressure disorders, demyelinating MS-lesions, hyperprolactinaemia, slow wound healing, sicca syndrome, osteoporosis. No familiarity for bone lesions. In 2007 her first son (21y/o) began to complain pain at limbs. The young man presented the same bone lesions as the mother and shortening of the PR, prolactinoma, recurrent diarrhea, short stature, early puberty. Over the years numerous pathologies have been first hypothesized and then excluded: multiple sclerosis, bone metastases, Paget’s disease, celiac disease, McCune Albright, Camurati-Engelmann syndrome, mitochondrial disease. No conclusive diagnosis despite the thousands of kilometers traveled, the numerous experts heard and the countless examinations carried out by the patients.Results:In September 2009, the patients had been investigated at the NIH (Washington D.C.) during the “Undiagnosed Diseases Program” but without results until 2013 when the patients were informed of the detection of an ATP6V1H gene mutation never described before in humans. The gene encodes a vacuolar ATPase, a multimeric enzyme that plays several roles: is involved in endocytosis, intracellular trafficking, and protein degradation and energy production, appears to be a risk factor in the development of dyslipidemias and type II diabetes, has a bone resorption function. Also in the patient’s father were founded the same mutation and asymptomatic bone lesions. In 2016 and 2017 studies have reported mouse models of osteoporosis that were generated by knocking out the ATP6V1H gene.Conclusion:from this case it is possible to understand the difficulty of diagnosing a rare disease, the need of an international collaboration in research. From these studies it can be deduced moreover that the ATP6V1H gene could be an important target for therapeutic interventions aimed at preventing bone resorption and treating osteoporosis; evidence to support exploration of MMP9 and MMP13 as therapeutic targets for patients with ATP6V1H deficiency.This mutation seems to affect only one family, but it is possible that the penetrance of the disease-causing mutation is variable. In literature is reported an enhanced expression of MMP-9 in a variety of autoimmune diseases and neurological pathologies (2) therefore the mutation can be at the basis of other much more common pathologies.References:[1]Zhang Y, Huang H, Zhao G, Yokoyama T, Vega H, Huang Y, Sood R, Bishop K, Maduro V, Accardi J, Toro C, Boerkoel CF, Lyons K, Gahl WA, Duan X, Malicdan MC, Lin S. ATP6V1H Deficiency Impairs Bone Development through Activation of MMP9 and MMP13. PLoS Genet. 2017 Feb 3;13(2):e1006481. doi: 10.1371/journal.pgen.1006481.[2]Ram M, Sherer Y, Shoenfeld Y. Matrix metalloproteinase-9 and autoimmune diseases. J Clin Immunol. 2006 Jul;26(4):299-307. doi: 10.1007/s10875-006-9022-6.Disclosure of Interests:Gilda Sandri: None declared, Lorenza Belletti: None declared, Michele Cavedoni: None declared, Claudio Galluzzo: None declared, stefano bruni Consultant of: Genzyme, Employee of: Genzyme, Maria Teresa Mascia: None declared

scholarly journals Diagnostic Value of Whole-Body MRI Short Protocols in Bone Lesion Detection in Multiple Myeloma Patients

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1053
Author(s):  
Davide Ippolito ◽  
Teresa Giandola ◽  
Cesare Maino ◽  
Davide Gandola ◽  
Maria Ragusi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow Involvement ◽  
Bone Lesion ◽  
Diagnostic Value ◽  
Lesion Detection ◽  
Lower Limbs ◽  
Whole Body ◽  
Bone Lesions ◽  
Whole Body Mri ◽  
Mri Protocol

The aim of the study is to evaluate the effectiveness of short whole-body magnetic resonance imaging (WBMRI) protocols for the overall assessment of bone marrow involvement in patients with multiple myeloma (MM), in comparison with standard whole-body MRI protocol. Patients with biopsy-proven MM, who underwent a WBMRI with full-body coverage (from vertex to feet) were retrospectively enrolled. WBMRI images were independently evaluated by two expert radiologists, in terms of infiltration patterns (normal, focal, diffuse, and combined), according to location (the whole skeleton was divided into six anatomic districts: skull, spine, sternum and ribs, upper limbs, pelvis and proximal two-thirds of the femur, remaining parts of lower limbs) and lytic lesions number (<5, 5–20, and >20). The majority of patients showed focal and combined infiltration patterns with bone lesions predominantly distributed in the spine and pelvis. As skull and lower limbs are less frequently involved by focal bone lesions, excluding them from the standard MRI protocol allows to obtain a shorter protocol, maintaining a good diagnostic value.

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