Novel FLNB Variants in Seven Argentinian Cases with Spondylocarpotarsal Synostosis Syndrome

Abstract

Spondylocarpotarsal synostosis syndrome (SCT) is a very rare skeletal dysplasia characterized by vertebral, carpal, and tarsal fusion; growth retardation; and mild dysmorphic facial features. Variants in FLNB, MYH3, and RFLNA have been implicated in this dysplasia. We report the clinical and radiological follow-up of seven SCT pediatric cases associated with biallelic FLNB variants, from four Argentinian families. The seven cases share previously described facial characteristics: round facies, large eyes, and wide based nose; all of them had variable height deficit, in one case noted early in life. Other findings included clinodactyly, joint limitation without bone fusion, neurosensorial hearing loss, and ophthalmological compromise. All cases presented with spinal fusion with variable severity and location, carpal bones coalition, and also delay in carpal ossification. The heterozygous carrier parents had normal height values to −2.5 score standard deviation, without skeletal defects detected. Three different FLNB variants, one nonsense and two frameshift, were detected, all of which were predicted to result in a truncated protein or are degraded by nonsense mediated decay. All cases had at least one copy of the nonsense variant, c.1128C> G; p. (Tyr376*), suggesting the presence of a common ancestor.

Keywords

spondylocarpotarsal synostosis syndrome - filamin B - carpal coalition - scoliosis - skeletal dysplasia

Ethical Approval

This is an observational study. Study approval was obtained from local ethical committees.

Patient Consent

All participants provided informed consent for the performed studies.

Authors' Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Ramos-Mejia Rosario, del Pino Mariana, Abbate Silvina, Obregon M.Gabriela, and Fano Virginia. Genetic studies were performed by Heath Karen E. and Aza-carmona Miriam. The first draft of the manuscript was written by Ramos-Mejia Rosario, and all authors commented on previous versions of the manuscript. All authors revised the manuscript critically and approved the final version. All of them agree to be accountable for all aspects of the work.

Publikationsverlauf

Eingereicht: 20. Mai 2022

Angenommen: 08. November 2022

Artikel online veröffentlicht:
15. Dezember 2022

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