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Bone. 2018 Feb;107:161-171. doi: 10.1016/j.bone.2017.11.012. Epub 2017 Nov 21.

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

Author information

1
Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St. Louis, MO 63110, USA; Department of Clinical Genetics, Division of Human Genetics and Genome Research, Centre of Excellence of Human Genetics, National Research Centre, Cairo, Egypt.
2
Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St. Louis, MO 63110, USA.
3
Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St. Louis, MO 63110, USA.
4
Mallinckrodt Institute of Radiology at St. Louis Children's Hospital, Washington University School of Medicine, St Louis, MO 63110, USA.
5
Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63110, USA.
6
Division of Pediatric Endocrinology and Metabolism, Washington University School of Medicine, St. Louis, MO 63110, USA.
7
Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
8
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
9
Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
10
Department of Cardiometabolic Disorders, Amgen Inc., Thousand Oaks, CA 91320, USA.
11
Division of Plastic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
12
Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
13
Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: mshinawi@wustl.edu.

Abstract

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 ~2months-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 15months. Additional reports must further elucidate the phenotype, explore any genotype-phenotype correlation, and evaluate treatments.

KEYWORDS:

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

PMID:
29175271
PMCID:
PMC5987759
[Available on 2019-02-01]
DOI:
10.1016/j.bone.2017.11.012

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