Long-term impact of FN1-related spondylometaphyseal dysplasia, corner fracture type (SMD-CF).

Variants in fibronectin 1 (FN1) are known to cause a rare skeletal dysplasia named spondylometaphyseal dysplasia, corner fracture type (SMD-CF). Only 21 cases have been described in the literature up to now. We describe a new case who is, to our knowledge, one of the oldest SMD-CF patients, and present a chronological timeline of major known medical events. The index case is a 55-year-old female with short stature (-2.79 SD), developmental coxa valga, and waddling gait. Next-generation sequencing identified a heterozygous single-nucleotide likely pathogenic variant in the FN1 gene: NM_212482.4(FN1):c.693C>G p.(Cys231Trp). Prior radiograph investigations revealed multiple corner fracture-like lesions throughout childhood. Patient presented with two new features - pectus excavatum and optic disc drusen, which have not been reported earlier to occur in FN1 SMD-CF individuals. Our patient underwent two hip arthroplasties at the age of 48 due to hip dysplasia and progressive osteoarthritis secondary to SMD-CF. Our report shows that long-term impacts of FN1 SMD-CF include progressive osteoarthritis, ophthalmologic findings and cardiac complications.