| Summary: | 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.
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