Analysis of children with familial short stature: who should be indicated for genetic testing?
Familial short stature (FSS) describes vertically transmitted growth disorders. Traditionally, polygenic inheritance is presumed, but monogenic inheritance seems to occur more frequently than expected. Clinical predictors of monogenic FSS have not been elucidated. The aim of the study was to identif...
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| Format: | Article |
| Language: | English |
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Bioscientifica
2023-10-01
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| Series: | Endocrine Connections |
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| Online Access: | https://ec.bioscientifica.com/view/journals/ec/12/10/EC-23-0238.xml |
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| author | Lukas Plachy Lenka Petruzelkova Petra Dusatkova Klara Maratova Dana Zemkova Lenka Elblova Vit Neuman Stanislava Kolouskova Barbora Obermannova Marta Snajderova Zdenek Sumnik Jan Lebl Stepanka Pruhova |
| author_facet | Lukas Plachy Lenka Petruzelkova Petra Dusatkova Klara Maratova Dana Zemkova Lenka Elblova Vit Neuman Stanislava Kolouskova Barbora Obermannova Marta Snajderova Zdenek Sumnik Jan Lebl Stepanka Pruhova |
| author_sort | Lukas Plachy |
| collection | DOAJ |
| description | Familial short stature (FSS) describes vertically transmitted growth disorders. Traditionally, polygenic inheritance is presumed, but monogenic inheritance seems to occur more frequently than expected. Clinical predictors of monogenic FSS have not been elucidated. The aim of the study was to identify the monogenic etiology and its clinical predictors in FSS children. Of 747 patients treated with growth hormone (GH) in our center, 95 with FSS met the inclusion criteria (pretreatment height ≤−2 SD in child and his/her shorter parent); secondary short stature and Turner/Prader–Willi syndrome were excluded criteria. Genetic etiology was known in 11/95 children before the study, remaining 84 were examined by next-generation sequencing. The results were evaluated by American College of Medical Genetics and Genomics (ACMG) guidelines. Nonparametric tests evaluated differences between monogenic and non-monogenic FSS, an ROC curve estimated quantitative cutoffs for the predictors. Monogenic FSS was confirmed in 36/95 (38%) children. Of these, 29 (81%) carried a causative genetic variant affecting the growth p late, 4 (11%) a variant affecting GH–insulin-like growth factor 1 (IGF1) axis and 3 (8%) a variant in miscellaneous genes. Lower shorter parent’s height (P = 0.015) and less delayed bone age (BA) before GH treatment (P = 0.026) predicted monogenic FSS. In children with BA delayed less than 0.4 years and with shorter parent’s heights ≤−2.4 SD, monogenic FSS was revealed in 13/16 (81%) cases. To conclude, in FSS children treated with GH, a monogenic etiology is frequent, and gene variants affecting the growth plate are the most common. Shorter parent’s height and BA are clinical predictors of monogenic FSS . |
| first_indexed | 2024-03-11T18:12:51Z |
| format | Article |
| id | doaj.art-078154ffc4e1414d9ee692c4d3a535ef |
| institution | Directory Open Access Journal |
| issn | 2049-3614 |
| language | English |
| last_indexed | 2024-03-11T18:12:51Z |
| publishDate | 2023-10-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj.art-078154ffc4e1414d9ee692c4d3a535ef2023-10-16T10:26:09ZengBioscientificaEndocrine Connections2049-36142023-10-01121018https://doi.org/10.1530/EC-23-0238Analysis of children with familial short stature: who should be indicated for genetic testing?Lukas Plachy0Lenka Petruzelkova1Petra Dusatkova2Klara Maratova3Dana Zemkova4Lenka Elblova5Vit Neuman6Stanislava Kolouskova7Barbora Obermannova8Marta Snajderova9Zdenek Sumnik10Jan Lebl11Stepanka Pruhova12Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech RepublicDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech RepublicDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech RepublicDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech RepublicDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech RepublicDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech RepublicDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech RepublicDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech RepublicDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech RepublicDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech RepublicDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech RepublicDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech RepublicDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech RepublicFamilial short stature (FSS) describes vertically transmitted growth disorders. Traditionally, polygenic inheritance is presumed, but monogenic inheritance seems to occur more frequently than expected. Clinical predictors of monogenic FSS have not been elucidated. The aim of the study was to identify the monogenic etiology and its clinical predictors in FSS children. Of 747 patients treated with growth hormone (GH) in our center, 95 with FSS met the inclusion criteria (pretreatment height ≤−2 SD in child and his/her shorter parent); secondary short stature and Turner/Prader–Willi syndrome were excluded criteria. Genetic etiology was known in 11/95 children before the study, remaining 84 were examined by next-generation sequencing. The results were evaluated by American College of Medical Genetics and Genomics (ACMG) guidelines. Nonparametric tests evaluated differences between monogenic and non-monogenic FSS, an ROC curve estimated quantitative cutoffs for the predictors. Monogenic FSS was confirmed in 36/95 (38%) children. Of these, 29 (81%) carried a causative genetic variant affecting the growth p late, 4 (11%) a variant affecting GH–insulin-like growth factor 1 (IGF1) axis and 3 (8%) a variant in miscellaneous genes. Lower shorter parent’s height (P = 0.015) and less delayed bone age (BA) before GH treatment (P = 0.026) predicted monogenic FSS. In children with BA delayed less than 0.4 years and with shorter parent’s heights ≤−2.4 SD, monogenic FSS was revealed in 13/16 (81%) cases. To conclude, in FSS children treated with GH, a monogenic etiology is frequent, and gene variants affecting the growth plate are the most common. Shorter parent’s height and BA are clinical predictors of monogenic FSS .https://ec.bioscientifica.com/view/journals/ec/12/10/EC-23-0238.xmlfamilial short staturenext-generation sequencinggrowth plate disordersgh treatmentpredictors of monogenic short stature |
| spellingShingle | Lukas Plachy Lenka Petruzelkova Petra Dusatkova Klara Maratova Dana Zemkova Lenka Elblova Vit Neuman Stanislava Kolouskova Barbora Obermannova Marta Snajderova Zdenek Sumnik Jan Lebl Stepanka Pruhova Analysis of children with familial short stature: who should be indicated for genetic testing? Endocrine Connections familial short stature next-generation sequencing growth plate disorders gh treatment predictors of monogenic short stature |
| title | Analysis of children with familial short stature: who should be indicated for genetic testing? |
| title_full | Analysis of children with familial short stature: who should be indicated for genetic testing? |
| title_fullStr | Analysis of children with familial short stature: who should be indicated for genetic testing? |
| title_full_unstemmed | Analysis of children with familial short stature: who should be indicated for genetic testing? |
| title_short | Analysis of children with familial short stature: who should be indicated for genetic testing? |
| title_sort | analysis of children with familial short stature who should be indicated for genetic testing |
| topic | familial short stature next-generation sequencing growth plate disorders gh treatment predictors of monogenic short stature |
| url | https://ec.bioscientifica.com/view/journals/ec/12/10/EC-23-0238.xml |
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