Kyphoscoliotic Ehlers-Danlos syndrome due to a novel homozygous PLOD1 variant: severe vascular involvement and molecular diagnosis.

BACKGROUND

Kyphoscoliotic Ehlers-Danlos syndrome (kEDS, OMIM: #225400) is a rare subtype of Ehlers-Danlos syndrome characterized by joint hypermobility and spinal deformity, with occasional vascular complications. The rarity of vascular phenotypes in kEDS often leads to low clinical suspicion, contributing to delayed diagnosis and poor outcomes.

CASE PRESENTATION: We report a 13-year-old boy who presented with joint laxity, scoliosis, blue sclerae, and pectus excavatum, and who ultimately succumbed to aortic rupture. Initial whole-exome sequencing (WES) and copy number variation (CNV) analysis failed to identify a causative variant, and genes associated with Marfan syndrome were excluded by WES and multiplex ligation-dependent probe amplification (MLPA). Upon re-analysis of the WES data, however, a homozygous deletion spanning exons 15-16 of PLOD1 was detected and subsequently confirmed by quantitative PCR.

CONCLUSIONS

This case demonstrates that small exon deletions in PLOD1 may not be reliably detected by routine WES/CNV pipelines, leading to diagnostic delay, and underscores the underrecognized vascular risk in kEDS. Clinicians should maintain vigilance for vascular complications in patients with kEDS and consider re-analysis strategies to ensure timely diagnosis and appropriate genetic counseling.