Novel mutations in geleophysic dysplasia type 1

Pediatr Dev Pathol. 2014 May-Jun;17(3):209-16. doi: 10.2350/13-08-1370-CR.1. Epub 2013 Nov 19.


Geleophysic dysplasia (GD) is a rare genetic disorder characterized by acromelic dysplasia. Geleophysic dysplasia type 1 (MIM 231050) is autosomal recessive and is caused by homozygous or compound heterozygous mutation in the ADAMTSL2 (a disintegrin and metalloproteinase with thrombosponding repeats-like 2) gene. Geleophysic dysplasia type 2 (MIM 614185) is autosomal dominant and is caused by heterozygous mutation in the fibrillin 1 (FBN1) gene. Here, we present the clinical and histopathologic findings in a child with GD with newly identified ADAMTSL2 mutations. The 1st mutation was probably a pathogenic one, c.[1934G>A] p.[Arg645His], located in exon 13; the 2nd, in intron 8, was probably changing a splice site. While the light and electron microscopic findings were similar to those previously described, hydrocephalus due to aqueductal stenosis might be a new associated finding in these patients. This child with these 2 novel mutations also had an aggressive clinical course with early-onset progressive cardiac valvular disease.

Keywords: ADAMTSL2; congenital heart disease; geleophysic dysplasia.

Publication types

  • Case Reports

MeSH terms

  • ADAM Proteins / genetics*
  • ADAMTS Proteins
  • Abnormalities, Multiple / genetics
  • Bone Diseases, Developmental / genetics*
  • Bone Diseases, Developmental / pathology*
  • Humans
  • Infant
  • Limb Deformities, Congenital / genetics*
  • Limb Deformities, Congenital / pathology*
  • Male
  • Mutation


  • ADAM Proteins
  • ADAMTS Proteins
  • ADAMTSL2 protein, human

Supplementary concepts

  • Acromicric dysplasia