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.

Clinical Characteristics of Short-Stature Patients With an NPR2 Mutation and the Therapeutic Response to rhGH

2020 ◽  
Author(s):  
Xiaoan Ke ◽  
Hanting Liang ◽  
Hui Miao ◽  
Hongbo Yang ◽  
Linjie Wang ◽  
...  
Keyword(s):  
Short Stature ◽  
Skeletal Dysplasia ◽  
Clinical Characteristics ◽  
Therapeutic Response ◽  
Catalytic Domain ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Heterozygous Mutation ◽  
Causative Gene ◽  
Rhgh Treatment

Abstract Context The natriuretic peptide receptor 2 gene (NPR2) is a causative gene of idiopathic short stature (ISS) with an incidence rate of 2% to 6%. The clinical characteristics of patients with NPR2 heterozygous mutations are atypical, and data on the efficacy of recombinant human growth hormone (rhGH) treatment in patients with NPR2 mutations are limited. Objectives This work reports 6 cases with NPR2 mutation and explores the characteristics of patients with an NPR2 mutation and their therapeutic response to rhGH. Design, Settings, and Patients Six Chinese short-stature patients in our hospital with NPR2 mutations by whole-exome sequencing were included. We also searched all previously published NPR2 mutation cases as of August 10, 2020, and information about their medical history, mutations, and rhGH treatment were recorded and summarized. Results The clinical characteristics of patients with an NPR2 heterozygous mutation mainly included short stature, facial anomalies, and skeletal dysplasia. Skeletal dysplasia mainly included brachydactyly (56.2%), shortened metacarpals or metatarsals (particularly fourth to fifth; 26.1%), and clinodactyly (21.7%). rhGH treatment significantly improved the height SD score (SDS) of patients with NPR2 heterozygous mutations (median, –2.1 vs –2.9, P < .001), especially in girls. The height SDS change correlated negatively with initial age of treatment (r = –0.477; P = .034), and height SDS change of patients with NPR2 heterozygous mutations in the carboxyl-terminal guanylyl cyclase catalytic domain was significantly higher than that of the extracellular ligand-binding region domain (median, 1.9 vs 0.6, P = .019). Conclusions ISS patients with skeletal deformities should be tested for an NPR2 mutation. rhGH treatment is beneficial for short-stature patients with NPR2 heterozygous mutations and needs further study.

Specialty Drugs for the Treatment of Short Stature in Children—Pros, Cons, and Perspectives for the Future

2010 ◽  
Vol 06 (01) ◽  
pp. 78
Author(s):  
Michaela B Koontz ◽  
Leona Cuttler ◽  
◽  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Hormone Deficiency ◽  
Current Status ◽  
Current Evidence ◽  
Recombinant Human Insulin ◽  
Growth Hormone Insensitivity ◽  
Severe Short Stature

Specialty drugs are generally defined as medications that involve special drug handling and/or parenteral administration and are typically used to treat complex medical conditions. They are typically biologicals, often very expensive, and generally prescribed by specialists. The recent surge in use of specialty pharmaceuticals has placed these drugs in the spotlight as policy-makers struggle to contain healthcare costs. Specialty drugs are central to discussions about optimal ways to manage childhood short stature; recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor-1 (rhIGF-1)—specialty drugs with annual prices of $20,000 to $30,000 per child—are available to treat childhood short stature from specific causes. rhGH and rhIGF-1 revolutionized treatment of severe short stature resulting from growth hormone deficiency and growth hormone insensitivity, respectively. Over the past 20 years, use of rhGH has expanded to other conditions. Expanded use of the newer rhIGF-1 may occur in an analogous manner. This article reviews the background, current status, and potential for these drugs in view of current evidence and policies.

The effect of treatment with recombinant human growth hormone (rhGH) on linear growth and adult height in children with idiopathic short stature (ISS): a systematic review and meta-analysis

2020 ◽  
Vol 33 (12) ◽  
pp. 1577-1588
Author(s):  
George Paltoglou ◽  
Ioannis Dimitropoulos ◽  
Georgia Kourlaba ◽  
Evangelia Charmandari
Keyword(s):  
Systematic Review ◽  
Growth Hormone ◽  
Short Stature ◽  
Human Growth Hormone ◽  
Adult Height ◽  
Linear Growth ◽  
Meta Analysis ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Idiopathic Short Stature

AbstractObjectivesIdiopathic short stature (ISS) is a recognized, albeit a controversial indication for treatment with recombinant human growth hormone (rhGH).The objective of the present study was to conduct a systematic review of the literature and meta-analyses of selected studies about the use of rhGH in children with ISS on linear growth and adult height (AH).MethodsA systematic literature search was conducted to identify relevant studies published till February 28, 2017 in the following databases: Medline (PubMed), Scopus and Cochrane Central Registry of Controlled Trials. After exclusion of duplicate studies, 3,609 studies were initially identified. Of those, 3,497 studies were excluded during the process of assessing the title and/or the abstract. The remaining 112 studies were evaluated further by assessing the full text; 21 of them fulfilled all the criteria in order to be included in the current meta-analysis.ResultsChildren who received rhGH had significantly higher height increment at the end of the first year, an effect that persisted in the second year of treatment and achieved significantly higher AH than the control group. The difference between the two groups was equal to 5.3 cm (95% CI: 3.4–7 cm) for male and 4.7 cm (95% CI: 3.1–6.3 cm) for female patients.ConclusionIn children with ISS, treatment with rhGH improves short-term linear growth and increases AH compared with control subjects. However, the final decision should be made on an individual basis, following detailed diagnostic evaluation and careful consideration of both risks and benefits of rhGH administration.

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.

Final Height of Idiopathic Short Stature Children Treated with Recombinant Human Growth Hormone (rhGH)

2011 ◽  
pp. P1-747-P1-747
Author(s):  
Thais C Martins ◽  
Cristiane N Lauretti ◽  
Ivo JP Arnhold ◽  
Berenice B Mendonca ◽  
Alexander AL Jorge
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Human Growth Hormone ◽  
Final Height ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Idiopathic Short Stature

scholarly journals Foramen Magnum Stenosis in Achondroplasia

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Choayb S ◽  
◽  
Adil H ◽  
El Haddad S ◽  
◽  
...  
Keyword(s):  
Sudden Death ◽  
Skull Base ◽  
Short Stature ◽  
Skeletal Dysplasia ◽  
Endochondral Ossification ◽  
Foramen Magnum ◽  
Severe Complication ◽  
Occipital Bone ◽  
Severe Morbidity ◽  
Cervicomedullary Junction

Achondroplasia is the most common hereditary skeletal dysplasia and is characterized by disproportionately short stature with rhizomelic short extremities [1]. The skull features include a narrowed foramen magnum, short skull base, and clivus [2]. Foramen magnum stenosis is a characteristic funding, secondary to an abnormal placement and premature fusion of the posterior synchondroses [1]. The second factor responsible for stenosis is a defect in endochondral ossification in the basiocciput that may result in an extension of the squamous occipital bone [2]. It can cause hydrocephalus and prominent emissary and meningeal veins (Figure 1). Figure 1: Sagittal T1WI revealing a narrowed stenosis of the foramen magnum and compression of the cervicomedullary junction. The most severe complication is the compression of the cervicomedullary junction, associated with severe morbidity and sudden death in younger children [1].

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