Pycnodysostosis: Natural history and management guidelines from 27 French cases and a literature review

Clin Genet. 2019 Oct;96(4):309-316. doi: 10.1111/cge.13591. Epub 2019 Jun 25.

Abstract

Pycnodysostosis is a lysosomal autosomal recessive skeletal dysplasia characterized by osteosclerosis, short stature, acro-osteolysis, facial features and an increased risk of fractures. The clinical heterogeneity of the disease and its rarity make it difficult to provide patients an accurate prognosis, as well as appropriate care and follow-up. French physicians from the OSCAR network have been asked to fill out questionnaires collecting molecular and clinical data for 27 patients issued from 17 unrelated families. All patients showed short stature (mean = -3.5 SD) which was more severe in females (P = .006). The mean fracture rate was moderate (0.21 per year), with four fractures in total average. About 75% underwent at least one surgery, with an average number of 2.1 interventions per patient. About 50% required non-invasive assisted ventilation due to sleep apnea (67%). About 29% showed psychomotor difficulties and 33% needed a school assistant or adapted schooling. No patient had any psychological evaluation or follow-up. Molecular data were available for 14 families. Growth hormone administration was efficient on linear growth in 40% of cases. We propose several axis of management, such as systematic cerebral MRI for Chiari malformation screening at diagnosis and regular psychological follow-up.

Keywords: CTSK; bone fragility; osteosclerosis; pycnodysostosis.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Alleles
  • Disease Management
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Mutation
  • Phenotype
  • Practice Guidelines as Topic
  • Pycnodysostosis / diagnosis*
  • Pycnodysostosis / genetics
  • Pycnodysostosis / therapy*
  • Radiography