Gottesman Gary S, Madson Katherine L, McAlister William H, Nenninger Angela, Wenkert Deborah, Mumm Steven, Whyte Michael P
Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St. Louis, Missouri.
Mallinckrodt Institute of Radiology, Washington University School of Medicine at St. Louis Children's Hospital, St. Louis, Missouri.
Am J Med Genet A. 2016 Apr;170A(4):978-85. doi: 10.1002/ajmg.a.37536. Epub 2016 Jan 14.
We report auricular ossification (AO) affecting the elastic cartilage of the ear as a newly recognized feature of osteoprotegerin (OPG)-deficiency juvenile Paget disease (JPD). AO and auricular calcification refer interchangeably to rigid pinnae, sparing the ear lobe, from various etiologies. JPD is a rare Mendelian disorder characterized by elevated serum alkaline phosphatase activity accompanied by skeletal pain and deformity from rapid bone turnover. Autosomal recessive transmission of loss-of-function mutations within TNFRSF11B encoding OPG accounts for most JPD (JPD1). JPD2 results from heterozygous constitutive activation of TNFRSF11A encoding RANK. Other causes of JPD remain unknown. In 2007, we reported a 60-year-old man with JPD1 who described hardening of his external ears at age 45 years, after 4 years of treatment with bisphosphonates (BPs). Subsequently, we noted rigid pinnae in a 17-year-old boy and 14-year-old girl, yet pliable pinnae in a 12-year-old boy, each with JPD1 and several years of BP treatment. Cranial imaging indicated cortical bone within the pinnae of both teenagers. Radiologic studies of our three JPD patients without mutations in TNFRSF11B showed normal auricles. Review of the JPD literature revealed possible AO in several reports. Two of our JPD1 patients had experienced difficult tracheal intubation, raising concern for mineralization of laryngeal elastic cartilage. Thus, AO is a newly recognized feature of JPD1, possibly exacerbated by BP treatment. Elastic cartilage at other sites in JPD1 might also ossify, and warrants investigation.
我们报告了耳骨化(AO)累及耳部弹性软骨,这是骨保护素(OPG)缺乏的青少年佩吉特病(JPD)新发现的一个特征。AO和耳钙化可互换使用,指各种病因导致的耳廓僵硬,耳垂不受影响。JPD是一种罕见的孟德尔疾病,其特征是血清碱性磷酸酶活性升高,伴有快速骨转换引起的骨骼疼痛和畸形。编码OPG的TNFRSF11B功能丧失突变的常染色体隐性遗传导致了大多数JPD(JPD1)。JPD2是由编码RANK的TNFRSF11A杂合性组成性激活引起的。JPD的其他病因尚不清楚。2007年,我们报告了一名患有JPD1的60岁男性,他在接受双膦酸盐(BP)治疗4年后,于45岁时描述其外耳变硬。随后,我们在一名17岁男孩和一名14岁女孩身上发现了僵硬的耳廓,但在一名12岁男孩身上发现耳廓柔软,他们均患有JPD1且接受了数年的BP治疗。头颅成像显示两名青少年的耳廓内有皮质骨。对我们三名TNFRSF11B无突变的JPD患者进行的放射学研究显示耳廓正常。对JPD文献的回顾显示,有几份报告中可能存在AO。我们的两名JPD1患者曾经历气管插管困难,这引发了对喉弹性软骨矿化的担忧。因此,AO是JPD1新发现的一个特征,可能因BP治疗而加重。JPD1其他部位的弹性软骨也可能发生骨化,值得研究。