Carcavilla Atilano, Santomé José L, Pinto Isabel, Sánchez-Pozo Jaime, Guillén-Navarro Encarna, Martín-Frías María, Lapunzina Pablo, Ezquieta Begoña
Servicio de Pediatría, Hospital Virgen de la Salud, Toledo, Spain; Laboratorio de Genética Molecular, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
Laboratorio de Genética Molecular, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
Rev Esp Cardiol (Engl Ed). 2013 May;66(5):350-6. doi: 10.1016/j.rec.2012.09.015. Epub 2013 Jan 11.
LEOPARD syndrome is an autosomal dominant condition related to Noonan syndrome, although it occurs less frequently. The aim of this study was to characterize the clinical and molecular features of a large series of LEOPARD syndrome patients.
We collected clinical data from 19 patients in 10 hospitals. Bidirectional sequencing analysis of PTPN11, RAF1, and BRAF focused on exons carrying recurrent mutations.
After facial dysmorphism, structural heart defects (88%) were the most common feature described. Hypertrophic cardiomyopathy (71%) was diagnosed more often than pulmonary valve stenosis (35%). Multiple lentigines or café au lait spots were found in 84% of the series, and deafness was diagnosed in 3 patients. Mutations in PTPN11 were identified in 16 (84%) patients (10 patients had the recurrent LEOPARD syndrome mutation, p.Thr468Met) (NP_002825.3T468M). Two other patients had a mutation in RAF, and 1 patient had a mutation in BRAF. When compared with other neurocardiofaciocutaneous syndromes, LEOPARD syndrome patients showed a higher prevalence of hypertrophic cardiomyopathy and cutaneous abnormalities, and a lower prevalence of pulmonary valve stenosis and short stature.
LEOPARD syndrome patients display distinctive features apart from multiple lentigines, such as a higher prevalence of hypertrophic cardiomyopathy and lower prevalence of short stature. Given its clinical implications, active search for hypertrophic cardiomyopathy is warranted in Noonan syndrome spectrum patients, especially in LEOPARD syndrome patients.
豹皮综合征是一种常染色体显性遗传病，与努南综合征相关，不过其发病率较低。本研究旨在描述大量豹皮综合征患者的临床和分子特征。
我们收集了10家医院19例患者的临床资料。对PTPN11、RAF1和BRAF进行双向测序分析，重点关注携带复发性突变的外显子。
除面部畸形外，结构性心脏缺陷（88%）是最常见的特征。肥厚型心肌病（71%）的诊断率高于肺动脉瓣狭窄（35%）。84%的患者发现有多个雀斑样痣或咖啡斑，3例患者被诊断为耳聋。16例（84%）患者检测到PTPN11突变（10例患者有复发性豹皮综合征突变，p.Thr468Met）（NP_002825.3T468M）。另外2例患者RAF有突变，1例患者BRAF有突变。与其他神经心血管皮肤综合征相比，豹皮综合征患者肥厚型心肌病和皮肤异常的患病率较高，而肺动脉瓣狭窄和身材矮小的患病率较低。
豹皮综合征患者除了有多个雀斑样痣外，还表现出独特的特征，如肥厚型心肌病患病率较高，身材矮小患病率较低。鉴于其临床意义，对于努南综合征谱系患者，尤其是豹皮综合征患者，有必要积极筛查肥厚型心肌病。
