A Cross-Sectional Cohort Study of the Effects of FGF23 Deficiency and Hyperphosphatemia on Dental Structures in Hyperphosphatemic Familial Tumoral Calcinosis.
A Cross-Sectional Cohort Study of the Effects of FGF23 Deficiency and Hyperphosphatemia on Dental Structures in Hyperphosphatemic Familial Tumoral Calcinosis.
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DOI：
10.1002/jbm4.10470
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发表时间：
2021-05
期刊：
影响因子：
3.8
通讯作者：
Collins MT
中科院分区：
文献类型：
--
作者：
Lee AE;Chu EY;Gardner PJ;Duverger O;Saikali A;Wang SK;Gafni RI;Hartley IR;Ten Hagen KG;Somerman MJ;Collins MT
高磷血症家族性肿瘤钙质沉着症 (HFTC) 是一种罕见的常染色体隐性遗传疾病，由 FGF23、GALNT3、KLOTHO 或 FGF23 自身抗体突变引起。突出的特征包括高血磷和钙化肿块，通常邻近大关节。牙齿缺陷已有报道，但尚未系统描述。美国国立卫生研究院对 17 名 HFTC 患者进行了详细的临床、生化、分子和牙科分析。牙齿研究包括口内照片和射线照片、高分辨率 μCT、组织学和扫描电子显微镜 (SEM)。开发了一个评分系统来评估牙齿表型的严重程度。 14 名可评估患者中有 13 名发现牙髓钙化。 13 名患者中有 12 名出现短根和中根隆起且根尖变薄。前磨牙受影响最严重。对五颗 HFTC 牙齿的 μCT 分析显示，与年龄和牙齿匹配的对照牙齿相比，HFTC 恒牙的牙髓密度增加了七倍，而牙髓体积减少了七倍。组织学显示极化的成牙本质细胞层丧失，牙髓腔消失，充满钙化物质。扫描电镜显示与对照牙齿相比，牙髓和牙骨质结构发生了改变，而牙釉质或牙本质结构没有差异。这项研究定义了 HFTC 的范围并证实了牙齿特征的高外显率。这些表型似乎与遗传/分子病因无关，表明高磷血症或 FGF23 缺乏可能是病理机制驱动因素，对牙根和牙髓结构具有显着影响，与磷酸盐和/或 FGF23 在牙齿发育中的作用一致。鉴于出现较早且外显率较高，认识到 HFTC 相关特征可能有助于早期诊断和治疗。 © 2021 作者。 JBMR Plus 由 Wiley periodicals LLC 出版。代表美国骨与矿物质研究学会。
Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder caused by mutations in FGF23, GALNT3, KLOTHO, or FGF23 autoantibodies. Prominent features include high blood phosphate and calcific masses, usually adjacent to large joints. Dental defects have been reported, but not systematically described. Seventeen patients with HFTC followed at the National Institutes of Health underwent detailed clinical, biochemical, molecular, and dental analyses. Studies of teeth included intraoral photos and radiographs, high‐resolution μCT, histology, and scanning electron microscopy (SEM). A scoring system was developed to assess the severity of tooth phenotype. Pulp calcification was found in 13 of 14 evaluable patients. Short roots and midroot bulges with apical thinning were present in 12 of 13 patients. Premolars were most severely affected. μCT analyses of five HFTC teeth revealed that pulp density increased sevenfold, whereas the pulp volume decreased sevenfold in permanent HFTC teeth compared with age‐ and tooth‐matched control teeth. Histology revealed loss of the polarized odontoblast cell layer and an obliterated pulp cavity that was filled with calcified material. The SEM showed altered pulp and cementum structures, without differences in enamel or dentin structures, when compared with control teeth. This study defines the spectrum and confirms the high penetrance of dental features in HFTC. The phenotypes appear to be independent of genetic/molecular etiology, suggesting hyperphosphatemia or FGF23 deficiency may be the pathomechanistic driver, with prominent effects on root and pulp structures, consistent with a role of phosphate and/or FGF23 in tooth development. Given the early appearance and high penetrance, cognizance of HFTC‐related features may allow for earlier diagnosis and treatment. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.