scholarly journals Two Patients with Severe Short Stature due to a FBN1 Mutation (p.Ala1728Val) with a Mild Form of Acromicric Dysplasia

2016 ◽  
Vol 86 (5) ◽  
pp. 342-348 ◽  
Author(s):  
Christiaan de Bruin ◽  
Courtney Finlayson ◽  
Mariana F.A. Funari ◽  
Gabriela A. Vasques ◽  
Bruna Lucheze Freire ◽  
...  
Keyword(s):  
Short Stature ◽  
Mild Form ◽  
Severe Short Stature ◽  
Acromicric Dysplasia

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 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 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 Walking and postural balance in adults with severe short stature due to isolated GH deficiency

2019 ◽  
Vol 8 (4) ◽  
pp. 416-424 ◽  
Author(s):  
Ananda A Santana-Ribeiro ◽  
Giulliani A Moreira-Brasileiro ◽  
Manuel H Aguiar-Oliveira ◽  
Roberto Salvatori ◽  
Vitor O Carvalho ◽  
...  
Keyword(s):  
Short Stature ◽  
Postural Balance ◽  
Fall Risk ◽  
Gh Deficiency ◽  
Muscle Tone ◽  
Receptor Gene ◽  
Leg Length ◽  
Timed Up And Go ◽  
Cross Sectional ◽  
Severe Short Stature

Objectives Walking and postural balance are extremely important to obtain food and to work. Both are critical for quality of life and ability to survive. While walking reflects musculoskeletal and cardiopulmonary systems, postural balance depends on body size, muscle tone, visual, vestibular and nervous systems. Since GH and IGF-I act on all these systems, we decided to study those parameters in a cohort of individuals with severe short stature due to untreated isolated GH deficiency (IGHD) caused by a mutation in the GHRH receptor gene. These IGHD subjects, despite reduction in muscle mass, are very active and have normal longevity. Methods In a cross-sectional study, we assessed walking (by a 6-min walk test), postural balance (by force platform) and fall risk (by the 'Timed Up and Go' test) in 31 IGHD and 40 matched health controls. Results The percentage of the walked distance measured in relation to the predicted one was similar in groups, but higher in IGHD, when corrected by the leg length. Absolute postural balance data showed similar velocity of unipodal support in the two groups, and better values, with open and closed eyes and unipodal support, in IGHD, but these differences became non-significant when corrected for height and lower-limb length. The time in 'Timed Up and Go' test was higher in IGHD cohort, but still below the cut-off value for fall risk. Conclusion IGHD subjects exhibit satisfactory walking and postural balance, without increase in fall risk.

scholarly journals Severe Short Stature in Two Siblings as the Presenting Sign of ACP5 Deficiency

2016 ◽  
Vol 85 (5) ◽  
pp. 358-362 ◽  
Author(s):  
Christiaan de Bruin ◽  
Zerrin Orbak ◽  
Melissa Andrew ◽  
Vivian Hwa ◽  
Andrew Dauber
Keyword(s):  
Short Stature ◽  
Severe Short Stature

scholarly journals High Prevalence of Growth Plate Gene Variants in Children With Familial Short Stature Treated With GH

2019 ◽  
Vol 104 (10) ◽  
pp. 4273-4281 ◽  
Author(s):  
Lukas Plachy ◽  
Veronika Strakova ◽  
Lenka Elblova ◽  
Barbora Obermannova ◽  
Stanislava Kolouskova ◽  
...  
Keyword(s):  
Short Stature ◽  
Growth Plate ◽  
Single Gene ◽  
Gene Variants ◽  
Genetic Etiology ◽  
Associated Proteins ◽  
Genetic Mechanisms ◽  
Standards And Guidelines ◽  
Minimum Height ◽  
Severe Short Stature

AbstractContextFamilial short stature (FSS) is a term describing a growth disorder that is vertically transmitted. Milder forms may result from the combined effect of multiple genes; more severe short stature is suggestive of a monogenic condition. The etiology of most FSS cases has not been thoroughly elucidated to date.ObjectivesTo identify the genetic etiology of severe FSS in children treated with GH because of the diagnosis of small for gestational age or GH deficiency (SGA/GHD).Design, Settings, and PatientsOf 736 children treated with GH because of GHD/SGA, 33 with severe FSS (life-minimum height −2.5 SD or less in both the patient and shorter parent) were included in the study. The genetic etiology was known in 5 of 33 children prior to the study [ACAN (in 2], NF1, PTPN11, and SOS1). In the remaining 28 of 33, whole-exome sequencing was performed. The results were evaluated using American College of Medical Genetics and Genomics standards and guidelines.ResultsIn 30 of 33 children (90%), we found at least one variant with potential clinical significance in genes known to affect growth. A genetic cause was elucidated in 17 of 33 (52%). Of these children, variants in growth plate-related genes were found in 9 of 17 [COL2A1, COL11A1, and ACAN (all in 2), FLNB, FGFR3, and IGF1R], and IGF-associated proteins were affected in 2 of 17 (IGFALS and HMGA2). In the remaining 6 of 17, the discovered genetic mechanisms were miscellaneous (TRHR, MBTPS2, GHSR, NF1, PTPN11, and SOS1).ConclusionsSingle-gene variants are frequent among families with severe FSS, with variants affecting the growth plate being the most prevalent.

Sign in / Sign up

Export Citation Format

Share Document