Frontometaphyseal dysplasia associated with the FLNA p.G1576R variant

This report presents a male patient with frontometaphyseal dysplasia (FMD) caused by a previously reported FLNA variant (NM_001456.4:c.4726G>A (p.Gly1576Arg)) that was maternally inherited. This finding directly contrasts with two previously reported observations of the same variant, which led to the suggestion that it is associated with a clinically distinct phenotype. Unlike these earlier descriptions, which did not report either signs of skeletal dysplasia or the typical facial features of FMD, the individual we report here exhibits, supraorbital hyperostosis, a skeletal dysplasia (small femoral epiphyses and bilateral pes cavus), retentio testis, reduced joint mobility, and a congenital cardiac anomaly (Ebstein anomaly). Furthermore, the previous cases documented uric acid renal stones and increased optic cup-to-disc ratio, both of which are not found in this patient. The previously reported individuals also had prominent keloid scarring, that is commonly encountered in individuals with FMD, but notably our patient exhibited hypertrophic scarring. The phenotype we report here suggests a broader phenotypic spectrum associated with this specific FLNA variant than previously recognized, challenging the view that it represents a separate syndrome of cardiac valvulopathy, keloid scarring, and joint mobility reduction and instead suggests it is likely best included within the spectrum of frontometaphyseal dysplasia.