Malaquias Alexsandra C, Ferreira Lize V, Souza Silvia C, Arnhold Ivo J P, Mendonça Berenice B, Jorge Alexander A L
Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM/42, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil.
Arq Bras Endocrinol Metabol. 2008 Jul;52(5):800-8. doi: 10.1590/s0004-27302008000500012.
Noonan Syndrome (NS) is one of the most common genetic syndromes and it is an important differential diagnosis in children with short stature, delayed puberty and cryptorchidism. NS is characterized by dysmorphic facial features, congenital heart defects and short stature, but there is a great variability in phenotype. NS may occur in a pattern consistent with autosomal dominant inheritance with almost complete penetrance. The diagnosis is based on a clinical score system proposed by van der Burgt e cols. in 1994. In recent years, germline mutations in the components of RAS-MAPK (mitogen activated protein kinase) pathway have been shown to be involved in the pathogenesis of NS. Mutations in PTPN11, KRAS, SOS1, RAF1 and MEK1 can explain 60-70% of NS molecular cause. Growth hormone therapy is proposed to correct the short stature observed in these patients. Recent studies suggest that the presence of PTPN11 mutations in patients with NS indicates a reduced growth response to short-term hrGH treatment. In this article, it is reviewed clinical and molecular aspects of NS and hrGH treatment for short stature.
努南综合征（NS）是最常见的遗传综合征之一，是身材矮小、青春期发育延迟和隐睾症患儿的重要鉴别诊断。NS的特征是面部畸形、先天性心脏缺陷和身材矮小，但表型存在很大差异。NS可能以常染色体显性遗传模式出现，几乎完全显性。诊断基于1994年范德伯格特等人提出的临床评分系统。近年来，RAS-MAPK（丝裂原活化蛋白激酶）通路成分的种系突变已被证明与NS的发病机制有关。PTPN11、KRAS、SOS1、RAF1和MEK1的突变可解释NS分子病因的60-70%。有人提议采用生长激素疗法来纠正这些患者中观察到的身材矮小。最近的研究表明，NS患者中PTPN11突变的存在表明对短期重组人生长激素治疗的生长反应降低。本文综述了NS的临床和分子方面以及身材矮小的重组人生长激素治疗。
