A case study of atypical Larsen syndrome with absent hallmark joint dislocations

摘要

Background A family with skeletal and craniofacial anomalies is presented. Whole‐exome sequencing (WES) analysis indicated a diagnosis of Larsen syndrome, although their clinical presentation does not include the hallmark joint dislocations typically observed in Larsen syndrome. Methods Patient consent for the sharing of de‐identified clinical and genetic information, along with use of photographs for publication, was obtained. WES and variant segregation analysis by WES were performed by commercial laboratory, GeneDx (Gaithersburg, MD), on peripheral blood samples from the proband, her brother, and her parents using methods detailed on their website for test XomeDx Whole Exome Sequencing Trio ( https://www.genedx.com/test-catalog/available-tests/xomedx-whole-exome-sequencing-trio/ ). WES uses next‐generation sequencing (NGS) technology to assess for variants within the coding regions, or exons, of approximately 23,000 genes. For the FLNB gene (NM_001457.3), 100% of the coding region was covered at a minimum of 10x. GeneDx uses Sanger sequencing to confirm NGS variants. Results WES revealed a heterozygous pathogenic variant, p.Glu227Lys (c.679GA), in the FLNB gene in three out of the four family members tested. This variant is associated with Larsen syndrome, a skeletal dysplasia condition with a wide range of phenotypic variability that usually includes congenital joint dislocations. Conclusion This is a highly unusual presentation of Larsen syndrome in which the identifying hallmark trait is absent in the patients’ phenotypes.