A new case of Greenberg dysplasia and literature review suggest that Greenberg dysplasia, dappled diaphyseal dysplasia, and Astley-Kendall dysplasia are allelic disorders

Mol Genet Genomic Med. 2020 Jun;8(6):e1173. doi: 10.1002/mgg3.1173. Epub 2020 Apr 18.

Abstract

Background: Greenberg dysplasia is a rare, autosomal recessive, prenatal lethal bone dysplasia caused by biallelic pathogenic variants in the lamin B receptor (LBR) gene. Pathogenic variants in LBR are also associated with Pelger-Huët anomaly, an autosomal dominant benign abnormality of the nuclear shape and chromatin organization of blood granulocytes, and Pelger-Huët anomaly with variable skeletal anomalies, a mild, regressing to moderate-severe autosomal recessive condition. Conditions with abnormal sterol metabolism and different genetic basis have clinical and radiographic features similar to Greenberg dysplasia, for example X-linked dominant chondrodysplasia punctata, Conradi-Hünermann type, and CHILD syndrome, and other conditions with unknown genetic etiology display very similar features, for example, dappled diaphyseal dysplasia and Astley-Kendall dysplasia.

Methods: We present a fetus with typical clinical and radiographic features of Greenberg dysplasia, and review the literature.

Results: Genetic testing confirmed the diagnosis Greenberg dysplasia: homozygosity for a pathogenic variant in LBR.

Conclusion: Comparing the clinical and radiographic phenotypes of Greenberg dysplasia, dappled diaphyseal dysplasia, and Astley-Kendall dysplasia, we suggest that these are allelic disorders.

Keywords: Greenberg dysplasia; LBR; Skeletal dysplasia; abnormal sterol metabolism.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Alleles
  • Chondrodysplasia Punctata / diagnostic imaging
  • Chondrodysplasia Punctata / genetics*
  • Chondrodysplasia Punctata / pathology
  • Dwarfism / diagnostic imaging
  • Dwarfism / genetics*
  • Dwarfism / pathology
  • Female
  • Fetus / pathology
  • Homozygote
  • Humans
  • Lamin B Receptor
  • Osteochondrodysplasias / diagnostic imaging
  • Osteochondrodysplasias / genetics*
  • Osteochondrodysplasias / pathology
  • Osteogenesis Imperfecta / diagnostic imaging
  • Osteogenesis Imperfecta / genetics*
  • Osteogenesis Imperfecta / pathology
  • Phenotype*
  • Pregnancy
  • Receptors, Cytoplasmic and Nuclear / genetics*

Substances

  • Receptors, Cytoplasmic and Nuclear

Supplementary concepts

  • Astley-Kendall syndrome
  • HEM dysplasia