ESPE Abstracts

Background: Proteoglycans are abundant and structurally complex bio macromolecules. They reside on the cell surface and are a major component of the extracellular matrix including bone. Defective formation of proteoglycans may case pleiotropic connective tissue syndromes including EDS-like and Larsen syndrome–like phenotypes.

Objective and hypotheses: We report on a girl with disproportionate short stature and joint laxity with pes planus and radial head dislocation. She was previously assigned to Spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1) which is characterised by vertebral abnormalities and ligamentous laxity that result in spinal misalignment and progressive severe kyphoscoliosis and respiratory compromise resulting in early death. The phenotype was similar, but except atlantoaxial hypermobility she did not develop scoliosis. This prompted us to Whole-Exom-Sequencing for a recessive mutation. Nonaxial skeletal involvement included elbow deformities with radial head dislocation, genu valgum, flat feet, and tapered fingers with spatulate distal phalanges. The girl had a round face, flat midface, prominent eyes with blue sclerae, and a long philtrum. Decreased bone density was confirmed in the patient (z-score at the hip −3.3). Final height was 130 cm (−5.3 SDS), weight 37 kg (<3^rd centile), normal cognitive function.

Results: We add an additional patient to a group of patients with short stature and joint laxity caused by mutations in the linker region of glycosaminoglycans (GAG) including syndromes with mutation in B3GAT3, B3GALT6 (Ehlers-Danlos- like), B4GALT6 (Ehlers-Danlos-like syndrome with kyphoskoliosis), and B4GALT7 (Larsen of Reunion Island syndrome).

Conclusion: Whole Exome Sequencing by SOLID 5500 (ThermoFIsher) revealed a homozygous missense mutation in B3GAT3-gene coding for Glucoronyl-transferase I (enzymatic step in the Golgi apparatus for a linkage region synthesis of proteoglycans i.e heparan sulfate): c.416C>T, p.Thr139Met.