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

Samina Yasin,Sadaf Naz,Outi Makitie

doi:10.1186/s12891-020-03890-2

Abstract

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.

Highlights

Loss of function or gain of function variants of Filamin B (FLNB) cause recessive or dominant skeletal disorders respectively
Our report expands the genetic spectrum of FLNB pathogenic variants
It indicates a need to assess the heights of other carriers of FLNB recessive variants to explore a possible role in idiopathic short stature

Summary

Introduction

Loss 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. Case presentation: We 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. Spondylocarpotarsal synostosis syndrome (SCT; OMIM # 272460) is an autosomal recessive disorder. Patients with SCT are characterized by short stature, vertebral fusion, scoliosis or lordosis and synostosis of carpal and tarsal bones. FLNB is composed of two actin-binding domains (ABD) at the N-terminus and 24 filamin repeat regions. There are two hinges interrupting these repeat regions (Fig. 1) [3]

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Discussion

Conclusion