Gnathodiaphyseal dysplasia: Severe atypical presentation with novel heterozygous mutation of the anoctamin gene (ANO5)

Ghada A. Otaify, Michael P. Whyte, Gary S. Gottesman, William H. McAlister, J. Eric Gordon, Abby Hollander, Marisa V. Andrews, Samir K. El-Mofty, Wei Shen Chen, Deborah V. Veis, Marina Stolina, Albert S. Woo, Panagiotis Katsonis, Olivier Lichtarge, Fan Zhang, Marwan Shinawi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


Gnathodiaphyseal dysplasia (GDD; OMIM #166260) is an ultra-rare autosomal dominant disorder caused by heterozygous mutation in the anoctamin 5 (ANO5) gene and features fibro-osseous lesions of the jawbones, bone fragility with recurrent fractures, and bowing/sclerosis of tubular bones. The physiologic role of ANO5 is unknown. We report a 5-year-old boy with a seemingly atypical and especially severe presentation of GDD and unique ANO5 mutation. Severe osteopenia was associated with prenatal femoral fractures, recurrent postnatal fractures, and progressive bilateral enlargement of his maxilla and mandible beginning at ~ 2 months-of-age that interfered with feeding and speech and required four debulking operations. Histopathological analysis revealed benign fibro-osseous lesions resembling cemento-ossifying fibromas of the jaw without psammomatoid bodies. A novel, de novo, heterozygous, missense mutation was identified in exon 15 of ANO5 (c.1553G > A; p.Gly518Glu). Our findings broaden the phenotypic and molecular spectra of GDD. Fractures early in life with progressive facial swelling are key features. We assessed his response to a total of 7 pamidronate infusions commencing at age 15 months. Additional reports must further elucidate the phenotype, explore any genotype-phenotype correlation, and evaluate treatments.

Original languageEnglish
Pages (from-to)161-171
Number of pages11
Publication statusPublished - Feb 2018
Externally publishedYes


  • Autosomal dominant
  • Bisphosphonates
  • Cemento-ossifying fibroma
  • Cherubism
  • Diaphyseal sclerosis
  • Fracture
  • Psammomatoid bodies

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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