Spondylocarpotarsal synostosis syndrome due to a novel loss of function FLNB variant: a case report

BackgroundLoss of function or gain of function variants of Filamin B (FLNB) cause recessive or dominant skeletal disorders respectively. Spondylocarpotarsal synostosis syndrome (SCT) is a rare autosomal recessive disorder characterized by short stature, fused vertebrae and fusion of carpal and tarsal bones. We present a novel FLNB homozygous pathogenic variant and present a carrier of the variant with short height.Case presentationWe describe a family with five patients affected with skeletal malformations, short stature and vertebral deformities. Exome sequencing revealed a novel homozygous frameshift variant c.2911dupG p.(Ala971GlyfsTer122) in FLNB, segregating with the phenotype in the family. The variant was absent in public databases and 100 ethnically matched control chromosomes. One of the heterozygous carriers of the variant had short stature.ConclusionOur report expands the genetic spectrum of FLNB pathogenic variants. It also indicates a need to assess the heights of other carriers of FLNB recessive variants to explore a possible role in idiopathic short stature.

Automated summary

Loss or gain of function variants in Filamin B (FLNB) can cause recessive or dominant skeletal disorders. Spondylocarpotarsal synostosis syndrome (SCT) is a rare autosomal recessive disorder characterized by short stature and bone fusion. A novel homozygous pathogenic variant in FLNB was identified in a family with skeletal malformations, short stature, and vertebral deformities. This report highlights the importance of assessing the heights of carriers of FLNB recessive variants in relation to idiopathic short stature.