Phenotype analysis of the Noonan syndrome (NS) related to RAF1 mutations demonstrates that a high proportion of cases exhibit severe lymphatic dysplasia and congenital heart disease, especially hypertrophic cardiomyopathy. Because of the difficulty of fetal phenotypic assessment, the percentage of cases with multisystemic prenatal presentation as well as the phenotypic variability may be underestimated. We describe a 35 weeks male preterm infant presenting with de novo missense mutation NM_002880.4(RAF1):c.770C>T (p.Ser257Leu), whose death occurred following birth. Antenatal ultrasound showed polyhydramnios, severe ascites, and tongue protrusion. Autopsy revealed multiple congenital anomalies including intrauterine growth restriction, hydrops fetalis, characteristic facial dysmorphia, short and webbed neck, hypertrichosis, severe lungs hypoplasia, thymic hyperplasia, hepato-splenomegaly, bilateral mild uretero-hydronephrosis, and mild pontocerebellar hypoplasia. Histology revealed increased hepatic hematopoiesis and iron deposits. This report confirms that NS may be associated with multisystem involvement and provides further evidence for the wide phenotypic variability associated with RAF1 variants.
Keywords: RAF1; autopsy; hepatomegaly; hydrops fetalis; pontocerebellar hypoplasia.
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