PMC4830924_01
GDD Patient 1. A and B: Frontal and lateral views of the patient. C: Panoramic radiograph showing extensive mixed density lesions and multiple impacted teeth. D: Axial CT slice demonstrating sclerotic lesions in the mandible. E. Sagittal CT slice showing maxillary hypoplasia and expansile mixed radiodensity lesions in the maxilla and mandible. F. Coronal CT slice showing displacement of the sinus floor causing maxillary sinus hypoplasia. G. 3D maximum intensity projection reconstruction of the maxillofacial CT scan demonstrating maxillary hypoplasia. H. Lateral radiograph of the femur showing a previous fracture.
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F1
The patient was partially edentulous with multiple impacted teeth (Figure 1C). Multiple well-defined, amorphous mixed radiodensity lesions were present predominantly in the tooth-bearing areas of the maxilla and mandible, with expansion and loss of normal trabecular architecture (Figures 1D-F). In the maxilla, the lesions protruded into the maxillary sinus lumen, causing considerable hypoplasia of the sinuses (Figure 1F).
Pedigree demonstrating the pattern of inheritance of the disease manifestations. Case 1 and case 2 are denoted by individuals II:2 and III:4, respectively.
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F2
The patient also provided a history of frequent fractures and jaw lesions in other family members (Figure 2) including his father, sister and all three of her children, and his 21-year-old son.
Modeled structure of the ANO5 wild type and C356Y mutant proteins. The black arrows point to the location of amino acid residue 356, located in the predicted extracellular domain. Note marked deviation in the structure of the extracellular loops of the mutant ANO5, compared with the wild-type structure.
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F3
The predicted structure of wild type ANO5 (Figure 3) was consistent with the putative structure of the anoctamin family members:eight transmembrane domains, the N- and C- terminals within the cytoplasm, and extracellular loops. Interestingly, the structure of the extracellular domains in the ANO5 C356Y mutant deviated markedly from the wild-type structure (Figure 3).
PMC4830924_02
GDD Patient 2. A and B: Frontal and lateral views showing expansion of the anterior mandible. C: Intraoral view showing multiple areas of expansion in the maxilla and mandible. D: 3D maximum intensity projection reconstruction of the maxillofacial CT scan showing maxillary hypoplasia, multiple impacted teeth, and expansile mixed radiodensity lesions. E. Axial slice showing expansile sclerotic lesions in the mandible. F. Sagittal CT slice showing expansile lesions in both jaws. G. Displacement of the sinus floor with resultant maxillary sinus hypoplasia. H. Panoramic radiograph showing extensive mixed radiodensity lesions and multiple impacted teeth.
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F4
Clinical examination revealed expansion of the anterior mandible (Figure 4A, 4B, and 4C). Clinical intraoral examination revealed multiple missing teeth, malocclusion, poor periodontal health, and mobility of several teeth (Figure 4C). Panoramic and CBCT depicted multiple impacted teeth (Figure 4D-H). Similar to his father, cementum/bone-like masses were present in the tooth-bearing areas of the jaws (Figure 4D-H).