Genotype–Phenotype Correlation in Children: The Impact of <i>FBN1</i> Variants on Pediatric Marfan Care
Currently, no reliable genotype–phenotype correlation is available for pediatric Marfan patients in everyday clinical practice. We investigated correlations of <i>FBN1</i> variants with the prevalence and age of onset of Marfan manifestations in childhood and differentiated three groups:...
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MDPI AG
2020-07-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/11/7/799 |
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| author | Veronika C. Stark Flemming Hensen Kerstin Kutsche Fanny Kortüm Jakob Olfe Peter Wiegand Yskert von Kodolitsch Rainer Kozlik-Feldmann Götz C. Müller Thomas S. Mir |
| author_facet | Veronika C. Stark Flemming Hensen Kerstin Kutsche Fanny Kortüm Jakob Olfe Peter Wiegand Yskert von Kodolitsch Rainer Kozlik-Feldmann Götz C. Müller Thomas S. Mir |
| author_sort | Veronika C. Stark |
| collection | DOAJ |
| description | Currently, no reliable genotype–phenotype correlation is available for pediatric Marfan patients in everyday clinical practice. We investigated correlations of <i>FBN1</i> variants with the prevalence and age of onset of Marfan manifestations in childhood and differentiated three groups: missense/in-frame, splice, and nonsense/frameshift variants. In addition, we differentiated missense variants destroying or generating a cysteine (cys-missense) and alterations not affecting cysteine. We categorized 105 <i>FBN1</i>-positive pediatric patients. Patients with cys-missense more frequently developed aortic dilatation (<i>p</i> = 0.03) requiring medication (<i>p</i> = 0.003), tricuspid valve prolapse (<i>p</i> = 0.03), and earlier onset of myopia (<i>p</i> = 0.02) than those with other missense variants. Missense variants correlated with a higher prevalence of ectopia lentis (<i>p</i> = 0.002) and earlier onset of pulmonary artery dilatation (<i>p</i> = 0.03) than nonsense/frameshift, and dural ectasia was more common in the latter (<i>p</i> = 0.005). Pectus excavatum (<i>p</i> = 0.007) appeared more often in patients with splice compared with missense/in-frame variants, while hernia (<i>p</i> = 0.04) appeared earlier in the latter. Findings on genotype–phenotype correlations in Marfan-affected children can improve interdisciplinary therapy. In patients with cys-missense variants, early medical treatment of aortic dilatation seems reasonable and early regular ophthalmologic follow-up essential. Patients with nonsense/frameshift and splice variants require early involvement of orthopedic specialists to support the growing child. |
| first_indexed | 2024-03-10T18:28:04Z |
| format | Article |
| id | doaj.art-dd31ae9b02ba466ba243533ff7891260 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T18:28:04Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-dd31ae9b02ba466ba243533ff78912602023-11-20T06:53:17ZengMDPI AGGenes2073-44252020-07-0111779910.3390/genes11070799Genotype–Phenotype Correlation in Children: The Impact of <i>FBN1</i> Variants on Pediatric Marfan CareVeronika C. Stark0Flemming Hensen1Kerstin Kutsche2Fanny Kortüm3Jakob Olfe4Peter Wiegand5Yskert von Kodolitsch6Rainer Kozlik-Feldmann7Götz C. Müller8Thomas S. Mir9Pediatric Cardiology, University Heart and Vascular Center Hamburg, Martinistrasse 52, 20246 Hamburg, GermanyPediatric Cardiology, University Heart and Vascular Center Hamburg, Martinistrasse 52, 20246 Hamburg, GermanyInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Martinistrasse 52, 20246 Hamburg, GermanyInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Martinistrasse 52, 20246 Hamburg, GermanyPediatric Cardiology, University Heart and Vascular Center Hamburg, Martinistrasse 52, 20246 Hamburg, GermanyPediatric Cardiology, University Heart and Vascular Center Hamburg, Martinistrasse 52, 20246 Hamburg, GermanyCardiology, University Heart and Vascular Center Hamburg, Martinistrasse 52, 20246 Hamburg, GermanyPediatric Cardiology, University Heart and Vascular Center Hamburg, Martinistrasse 52, 20246 Hamburg, GermanyPediatric Cardiology, University Heart and Vascular Center Hamburg, Martinistrasse 52, 20246 Hamburg, GermanyPediatric Cardiology, University Heart and Vascular Center Hamburg, Martinistrasse 52, 20246 Hamburg, GermanyCurrently, no reliable genotype–phenotype correlation is available for pediatric Marfan patients in everyday clinical practice. We investigated correlations of <i>FBN1</i> variants with the prevalence and age of onset of Marfan manifestations in childhood and differentiated three groups: missense/in-frame, splice, and nonsense/frameshift variants. In addition, we differentiated missense variants destroying or generating a cysteine (cys-missense) and alterations not affecting cysteine. We categorized 105 <i>FBN1</i>-positive pediatric patients. Patients with cys-missense more frequently developed aortic dilatation (<i>p</i> = 0.03) requiring medication (<i>p</i> = 0.003), tricuspid valve prolapse (<i>p</i> = 0.03), and earlier onset of myopia (<i>p</i> = 0.02) than those with other missense variants. Missense variants correlated with a higher prevalence of ectopia lentis (<i>p</i> = 0.002) and earlier onset of pulmonary artery dilatation (<i>p</i> = 0.03) than nonsense/frameshift, and dural ectasia was more common in the latter (<i>p</i> = 0.005). Pectus excavatum (<i>p</i> = 0.007) appeared more often in patients with splice compared with missense/in-frame variants, while hernia (<i>p</i> = 0.04) appeared earlier in the latter. Findings on genotype–phenotype correlations in Marfan-affected children can improve interdisciplinary therapy. In patients with cys-missense variants, early medical treatment of aortic dilatation seems reasonable and early regular ophthalmologic follow-up essential. Patients with nonsense/frameshift and splice variants require early involvement of orthopedic specialists to support the growing child.https://www.mdpi.com/2073-4425/11/7/799Marfan syndromechildhoodgenetic testing<i>FBN1</i> variantgenotype–phenotypevariant spectrum |
| spellingShingle | Veronika C. Stark Flemming Hensen Kerstin Kutsche Fanny Kortüm Jakob Olfe Peter Wiegand Yskert von Kodolitsch Rainer Kozlik-Feldmann Götz C. Müller Thomas S. Mir Genotype–Phenotype Correlation in Children: The Impact of <i>FBN1</i> Variants on Pediatric Marfan Care Genes Marfan syndrome childhood genetic testing <i>FBN1</i> variant genotype–phenotype variant spectrum |
| title | Genotype–Phenotype Correlation in Children: The Impact of <i>FBN1</i> Variants on Pediatric Marfan Care |
| title_full | Genotype–Phenotype Correlation in Children: The Impact of <i>FBN1</i> Variants on Pediatric Marfan Care |
| title_fullStr | Genotype–Phenotype Correlation in Children: The Impact of <i>FBN1</i> Variants on Pediatric Marfan Care |
| title_full_unstemmed | Genotype–Phenotype Correlation in Children: The Impact of <i>FBN1</i> Variants on Pediatric Marfan Care |
| title_short | Genotype–Phenotype Correlation in Children: The Impact of <i>FBN1</i> Variants on Pediatric Marfan Care |
| title_sort | genotype phenotype correlation in children the impact of i fbn1 i variants on pediatric marfan care |
| topic | Marfan syndrome childhood genetic testing <i>FBN1</i> variant genotype–phenotype variant spectrum |
| url | https://www.mdpi.com/2073-4425/11/7/799 |
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