Department of Endocrinology, Metabolism and Genetics, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Department of Genetic Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Orphanet J Rare Dis. 2023 Sep 11;18(1):284. doi: 10.1186/s13023-023-02878-0.
Cardio-facio-cutaneous (CFC) syndrome is a RASopathy subtype that presents with unique craniofacial dysmorphology, congenital heart disease, dermatologic abnormalities, growth retardation, and intellectual disability. This study describes the phenotypic spectrum of CFC in China and its association with CFC syndrome gene variants.
Twenty Chinese CFC patients, aged 0.6-9.5 years old, were included in this study and their clinical phenotypic spectrum was compared with that of 186 patients with CFC from non-Chinese ethnicities. All 20 Chinese patients with CFC carried de novo heterozygous BRAF, MAP2K1, and MAP2K2 variants. Two novel variants were detected and consistently predicted to be deleterious using bioinformatic tools. The clinical features of CFC in the Chinese patients included hypertrophic cardiomyopathy (2/20, 10%), pulmonary valve stenosis (2/20, 10%), curly or sparse hair (7/20, 35%), epilepsy (1/20, 5%), and hypotonia (10/20, 50%); these features were less frequently observed in Chinese patients than non-Chinese patients (p < 0.05). In contrast, feeding difficulties (19/20, 95%) were more frequently observed in the Chinese patients. Absent eyebrows and severe short stature were more common in patients with BRAF variants than in those with MAP2K1/2 variants. Facial recognition software was used to recognize most CFC patients using artificial intelligence.
This study identified novel and common variants in our cohort of 20 Chinese patients with CFC. We uncovered differences in clinical features between Chinese and non-Chinese patients and detected genotype-phenotype correlations among the BRAF and MAP2K1/2 variant subgroups. This is the largest cohort of Chinese CFC patients to our knowledge, providing new insights into a subtype of RASopathy.
心面指综合征（CFC）是一种 RAS 相关疾病，其特征为独特的颅面畸形、先天性心脏病、皮肤异常、生长发育迟缓以及智力障碍。本研究描述了中国 CFC 患者的表型谱及其与 CFC 综合征基因突变的关系。
本研究纳入了 20 名年龄为 0.6-9.5 岁的中国 CFC 患者，并与 186 名非中国血统的 CFC 患者进行了临床表型谱比较。所有 20 名中国 CFC 患者均携带新发性 BRAF、MAP2K1 和 MAP2K2 杂合突变。通过生物信息学工具，检测到并一致预测到两种新的变异是有害的。中国 CFC 患者的临床特征包括肥厚型心肌病（2/20，10%）、肺动脉瓣狭窄（2/20，10%）、卷发或稀疏头发（7/20，35%）、癫痫（1/20，5%）和低张力（10/20，50%）；与非中国患者相比，这些特征在中国患者中较少见（p<0.05）。相反，喂养困难（19/20，95%）在中国患者中更为常见。无眉毛和严重身材矮小在 BRAF 变异患者中比在 MAP2K1/2 变异患者中更为常见。面部识别软件使用人工智能识别出大多数 CFC 患者。
本研究在 20 名中国 CFC 患者的队列中发现了新的和常见的变异。我们揭示了中国和非中国患者之间临床特征的差异，并在 BRAF 和 MAP2K1/2 变异亚组中检测到了基因型-表型相关性。这是迄今为止中国最大的 CFC 患者队列，为 RAS 相关疾病的一个亚型提供了新的见解。
