Abstract：
Tricho-rhino-phalangeal syndrome (TRPS) is a rare malformation syndrome characterized by distinctive facial, ectodermal, and skeletal features. TRPS is divided into TRPS type I/III caused by pathogenic variants in TRPS1 and TRPS type II caused by contiguous gene deletions also spanning EXT1 and RAD21. Due to its rarity, knowledge of the clinical course of TRPS remains limited. Therefore, we collected and characterized a case series of 15 TRPS type I patients (median age at diagnosis 15 [interquartile range: 10-18] years, 11 females [73%]) seen at Aarhus University Hospital, Denmark, with a median follow-up period of 10 years. We estimated a minimum point prevalence of 0.5 in 100,000 (95% CI: 0.3-0.8 per 100,000) persons. Common craniofacial features included fine and sparse hair with a high anterior hairline, eyebrows with lateral thinning and a thicker medial part, prominent ears, a bulbous nose tip with small nasal alae, a low-hanging, and often wide columella, and a long philtrum with a thin upper vermillion. Specific skeletal features included short stature and deviating and short fingers with cone-shaped epiphyses and shortened metacarpals on radiographs. The most significant morbidity of the cohort was joint complaints, which were reported by all patients, often already before the TRPS diagnosis was established. We identified ten different TRPS1 variants including both frameshift/nonsense, missense, and splice-site variants, including seven variants not previously reported in the literature. In accordance with previous literature, no genotype-phenotype correlation was identified. The clinical trajectories were heterogeneous involving pediatrics, dermatology, orthopedic surgery, clinical genetics, and/or odontology, emphasizing that close multidisciplinary collaboration is essential for early diagnosis of TRPS and to ensure proper and timely patient care and counseling.
摘要：
三犀牛指骨综合征（TRPS）是一种罕见的畸形综合征，其特征是独特的面部，外胚层,和骨骼特征。TRPS分为由TRPS1中的致病性变体引起的TRPSI/III型和由也跨越EXT1和RAD21的连续基因缺失引起的TRPSII型。由于它的稀有性,对TRPS临床病程的了解仍然有限.因此,我们收集并表征了15例TRPSI型患者的病例系列（诊断为15[四分位距：10-18]岁，11名女性[73%])在奥胡斯大学医院就诊，丹麦,中位随访期为10年。我们估计最低点患病率为100,000人中的0.5人（95％CI：每100,000人中0.3-0.8人）。常见的颅面特征包括细密稀疏的头发和高的前发际线，眉毛外侧变薄，内侧较厚，突出的耳朵,带有小鼻翼的球形鼻尖，一个低垂的，通常是宽的小柱，和一个长的hiltrum，上面有一个细的朱红色。特定的骨骼特征包括身材矮小，偏斜和短手指，圆锥形骨phy和X线片上的掌骨缩短。该队列中最重要的发病率是联合投诉，所有患者都报告了，通常在TRPS诊断确定之前。我们确定了十种不同的TRPS1变体，包括移码/无义，错觉，和剪接位点变体，包括以前文献中未报道的七个变体。根据以前的文献，未发现基因型-表型相关性.涉及儿科的临床轨迹是异质的，皮肤病学,骨科手术,临床遗传学,和/或牙本质学，强调密切的多学科合作对于TRPS的早期诊断以及确保适当和及时的患者护理和咨询至关重要。
