Digilio M C, Lepri F, Baban A, Dentici M L, Versacci P, Capolino R, Ferese R, De Luca A, Tartaglia M, Marino B, Dallapiccola B
Medical Genetics and Pediatric Cardiology, Bambino Gesù Pediatric Hospital, IRCCS.
Mol Syndromol. 2011 Sep;1(6):282-289. doi: 10.1159/000331266. Epub 2011 Sep 14.
Diagnosis within Noonan syndrome and related disorders (RASopathies) still presents a challenge during the first months of life, since most clinical features used to differentiate these conditions become manifest later in childhood. Here, we retrospectively reviewed the clinical records referred to the first year of life of 57 subjects with molecularly confirmed diagnosis of RASopathy, to define the early clinical features characterizing these disorders and improve our knowledge on natural history. Mildly or markedly expressed facial features were invariably present. Congenital heart defects were the clinical issue leading to medical attention in patients with Noonan syndrome and LEOPARD syndrome. Feeding difficulties and developmental motor delay represented the most recurrent features occurring in subjects with cardiofaciocutaneous syndrome and Costello syndrome. Thin hair was prevalent among SHOC2 and BRAF mutation-positive infants. Café-au-lait spots were found in patients with LS and PTPN11 mutations, while keratosis pilaris was more common in individuals with SOS1, SHOC2 and BRAF mutations. In conclusion, some characteristics can be used as hints for suspecting a RASopathy during the first months of life, and individual RASopathies may be suspected by analysis of specific clinical signs. In the first year of life, these include congenital heart defects, severity of feeding difficulties and delay of developmental milestones, hair and skin anomalies, which may help to distinguish different entities, for their subsequent molecular confirmation and appropriate clinical management.
在努南综合征及相关疾病（RAS 病）中，出生后头几个月的诊断仍然具有挑战性，因为用于区分这些病症的大多数临床特征在儿童期后期才会显现出来。在此，我们回顾性分析了 57 例经分子确诊为 RAS 病的患者出生第一年的临床记录，以确定这些疾病的早期临床特征，并增进我们对其自然病史的了解。轻度或明显的面部特征总是存在。先天性心脏缺陷是努南综合征和豹皮综合征患者引起医疗关注的临床问题。喂养困难和发育性运动迟缓是心面皮肤综合征和科斯特洛综合征患者中最常见的特征。头发稀疏在 SHOC2 和 BRAF 突变阳性的婴儿中很普遍。咖啡牛奶斑在患有豹皮综合征和 PTPN11 突变的患者中出现，而毛发角化病在 SOS1、SHOC2 和 BRAF 突变的个体中更为常见。总之，一些特征可作为出生后头几个月怀疑患有 RAS 病的线索，通过分析特定临床体征可怀疑个别 RAS 病。在出生后的第一年，这些特征包括先天性心脏缺陷、喂养困难的严重程度和发育里程碑的延迟、毛发和皮肤异常，这可能有助于区分不同的疾病实体，以便随后进行分子确诊和适当的临床管理。
