Further evidence for attenuated phenotype with variants in the BMPER gene causing DSD: Case report and literature review

Eur J Med Genet. 2022 Apr;65(4):104470. doi: 10.1016/j.ejmg.2022.104470. Epub 2022 Feb 28.

Abstract

Diaphonospondylodysotosis (DSD) and ischiospinal dysostosis (ISD) are rare skeletal dysplasias with variants in the bone morphogenetic protein-binding endothelial regulator (BMPER). There is a continuum of clinical presentation, with DSD at the severe end of the spectrum whilst ISD is towards the milder end. Both are caused due to pathogenic variants in BMPER. Previous studies have reported 20 patients from 13 families. Common features in the cohort reported so far are spinal and rib anomalies but other findings illustrate phenotypic variation. Survival ranges from death within the neonatal period to alive and well at 19 years. We present three siblings with variable phenotype, adding to the evidence for a single definition of BMPER-related skeletal dysplasia. We highlight the need for ongoing care planning and guarded prognostication, with regular review by clinical teams.

Keywords: Advanced care planning; Bone diseases; Developmental; Genetic association studies; Genomic structural variation; Phenotype.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Carrier Proteins* / genetics
  • Dysostoses* / genetics
  • Humans
  • Phenotype
  • Spine / abnormalities

Substances

  • BMPER protein, human
  • Carrier Proteins