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

Abstract

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.679G>A), 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.

Perilunate dislocation in adult male with Larsen’s syndrome: A case report

“…LS is genetically heterogeneous and consists of an autosomal dominant disorder; however, autosomal recessive and sporadic disorders have also been reported [2][3][4]. Genetic testing is helpful in diagnosing LS patients with atypical or milder clinical manifestations [5]. LS manifests clinically by distinctive facial features, multiple joint dislocations of the hip, knee, and elbow joints, and spinal abnormalities, including scoliosis and cervical kyphosis.…”

An orthodontic perspective on Larsen syndrome

“…LS is genetically heterogeneous, and consists of autosomal recessive or autosomal dominant disorders caused by respective mutations in the CHST3, B4GALT7, and GZF1 genes [7], or in the FLNB gene [8][9][10][11]. Genetic testing of the presence of mutations in these genes provides a useful adjunct to the diagnosis of LS patients with atypical or milder clinical manifestations [9,10,12]. The prognosis in the autosomal dominant form is relatively favorable than that in the recessive form if patients are treated with orthopedic surgery, physical therapy, fixation in plaster, or procedures used to treat the various symptoms associated with LS.…”