Cardio-Facio-Cutaneous Syndrome: Does Genotype Predict Phenotype?
Cardio-Facio-Cutaneous Syndrome: Does Genotype Predict Phenotype?
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DOI：
10.1002/ajmg.c.30295
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发表时间：
2011-05-15
影响因子：
3.1
通讯作者：
Zenker, Martin
中科院分区：
文献类型：
--
作者：
Allanson, Judith E.;Anneren, Goran;Zenker, Martin
心面部皮肤综合征是一种主要由BRAF、MEK1和MEK2基因突变引起的散发性多发性先天性畸形/智力低下的疾病。KRAS和SHOC2的突变导致具有重叠特征的表型。在大约10%-30%的临床诊断为氟氯化碳的个体中，没有发现这些致病基因中的一个突变。先天性心脏病的基本特征包括先天性心脏缺陷、特征性面部外观和外胚层异常。其他特征包括严重的喂养问题无法茁壮成长，中度到严重的智力残疾，以及身材矮小和相对巨大的头畸形。首次描述于1986年，报告了100多名受影响的人。随着致病基因的发现，更多关于临床特征的信息出现了。然而，关于基因型-表型相关性的研究很少发表。这项对186名患有突变证实的氟氯化碳综合征的儿童和年轻人的临床研究是迄今为止报道的最大规模的研究。在140名个体中发现了BRAF突变(类似于75%)，而46名个体(类似于25%)存在MEK 1或MEK 2突变。年龄范围从6个月到32岁，最年长的个体是原始报告中的一名女性[Reynolds等人]。(1986)；《医学杂志》25：413-427]。虽然关于136人的一些临床数据已经在文献中，但有50人之前没有发表过。我们提供了表型广度的新细节，并讨论了每个基因型组中特定特征的频率。肺动脉狭窄是唯一表现出显著的基因-表型相关性的异常，在有BRAF突变的个体中更为常见。(C)2011年Wiley-Liss，Inc.
Cardio-facio-cutaneous (CFC) syndrome is a sporadic multiple congenital anomalies/mental retardation condition principally caused by mutations in BRAF, MEK1, and MEK2. Mutations in KRAS and SHOC2 lead to a phenotype with overlapping features. In approximately 10-30% of individuals with a clinical diagnosis of CFC, a mutation in one of these causative genes is not found. Cardinal features of CFC include congenital heart defects, a characteristic facial appearance, and ectodermal abnormalities. Additional features include failure to thrive with severe feeding problems, moderate to severe intellectual disability and short stature with relative macrocephaly. First described in 1986, more than 100 affected individuals are reported. Following the discovery of the causative genes, more information has emerged on the breadth of clinical features. Little, however, has been published on genotype-phenotype correlations. This clinical study of 186 children and young adults with mutation-proven CFC syndrome is the largest reported to date. BRAF mutations are documented in 140 individuals (similar to 75%), while 46 (similar to 25%) have a mutation in MEK 1 or MEK 2. The age range is 6 months to 32 years, the oldest individual being a female from the original report [Reynolds et al. (1986); Am J Med Genet 25:413-427]. While some clinical data on 136 are in the literature, 50 are not previously published. We provide new details of the breadth of phenotype and discuss the frequency of particular features in each genotypic group. Pulmonary stenosis is the only anomaly that demonstrates a statistically significant genotype-phenotype correlation, being more common in individuals with a BRAF mutation. (c) 2011 Wiley-Liss, Inc.