Rare bone diseases and their dental, oral, and craniofacial manifestations.
Hereditary diseases affecting the skeleton are heterogeneous in etiology and severity. Though many of these conditions are individually rare, the total number of people affected is great. These disorders often include dental-oral-craniofacial (DOC) manifestations, but the combination of the rarity and lack of in-depth reporting often limit our understanding and ability to diagnose and treat affected individuals. In this review, we focus on dental, oral, and craniofacial manifestations of rare bone diseases. Discussed are defects in 4 key physiologic processes in bone/tooth formation that serve as models for the understanding of other diseases in the skeleton and DOC complex: progenitor cell differentiation (fibrous dysplasia), extracellular matrix production (osteogenesis imperfecta), mineralization (familial tumoral calcinosis/hyperostosis hyperphosphatemia syndrome, hypophosphatemic rickets, and hypophosphatasia), and bone resorption (Gorham-Stout disease). For each condition, we highlight causative mutations (when known), etiopathology in the skeleton and DOC complex, and treatments. By understanding how these 4 foci are subverted to cause disease, we aim to improve the identification of genetic, molecular, and/or biologic causes, diagnoses, and treatment of these and other rare bone conditions that may share underlying mechanisms of disease.
National Institute for Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA brian.foster@nih.gov.
B L
BL
Foster
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
M S
MS
Ramnitz
Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
R I
RI
Gafni
Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
A B
AB
Burke
Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA Bone Health Program, Division of Orthopedics and Sports Medicine, Children's National Medical Center, Washington, DC, USA Division of Endocrinology and Diabetes, Children's National Medical Center, Washington, DC, USA.
A M
AM
Boyce
Office of Clinical Director, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
J S
JS
Lee
Department of Pediatric Dentistry, School of Dentistry, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
J T
JT
Wright
Department of Oral Medicine, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
S O
SO
Akintoye
National Institute for Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
M J
MJ
Somerman
Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
M T
MT
Collins
D001847:Bone Diseases / Q000235:genetics*; D002114:Calcinosis / Q000235:genetics; D005147:Facial Bones / Q000473:pathology*; D053098:Familial Hypophosphatemic Rickets / Q000235:genetics; D005357:Fibrous Dysplasia of Bone / Q000235:genetics; D006801:Humans; D006958:Hyperostosis, Cortical, Congenital / Q000235:genetics; D054559:Hyperphosphatemia / Q000235:genetics; D007014:Hypophosphatasia / Q000235:genetics; D009059:Mouth Diseases / Q000235:genetics*; D010013:Osteogenesis Imperfecta / Q000235:genetics; D010015:Osteolysis, Essential / Q000235:genetics; D035583:Rare Diseases; D012886:Skull / Q000473:pathology*; D014076:Tooth Diseases / Q000235:genetics*
Gorham-Stout disease; familial hypophosphatemic rickets; fibrous dysplasia of bone; hyperphosphatemic familial tumoral calcinosis; hypophosphatasia; osteogenesis imperfecta