■心-面-皮综合征(CFCS)是一种罕见的常染色体显性遗传障碍,主要由BRAF基因突变引起,由于其多方面的临床表现,构成了诊断挑战。
■为了阐明小儿CFCS患者的临床特征,扩大表型谱以增强早期诊断能力,同时还介绍了Genotye与相应表型严重程度之间的关系。
■对2015年1月至2022年3月重庆医科大学附属儿童医院4例CFCS患儿进行分析。进行全外显子组测序(WES)以鉴定可能的基因突变的类型和位置。使用脑电图(EEG)评估神经系统发育,磁共振成像(MRI)和Gesell发育评估。
■所有4名CFCS患者均表现出BRAF基因突变,表现为心脏畸形,独特的面部特征,皮肤和头发的变化,和神经异常。WES显示,特定的BRAF突变与其临床严重程度密切相关。三名患者表现出轻度症状(病例1-3,基因型I或II),表现出稳定性或轻微改善,而一名患者(病例4,基因型III)患有严重的表型,其特征是严重的神经和消化系统损害,导致生活质量显著下降,预后严峻。
■在CFCS患者中,严重的发育迟缓和癫痫发作是主要的神经系统特征,可能伴有睡眠期间持续的尖峰波(CSWS)和严重的睡眠障碍。CFCS通常预后不良,强调疾病意识和早期基因检测的重要性。
UNASSIGNED: Cardio-Facio-Cutaneous syndrome (CFCS) is a rare autosomal dominant genetic disorder primarily caused by BRAF gene mutations, posing diagnostic challenges due to its multifaceted clinical presentation.
UNASSIGNED: To elucidate the clinical characteristics of pediatric CFCS patients, expanding the phenotypic spectrum to enhance early diagnostic capabilities, while also presenting the relationship between genotye and corresponding phenotype severity.
UNASSIGNED: From January 2015 to March 2022, four children diagnosed with CFCS in Children\'s Hospital of Chongqing Medical University were included for analysis. Whole exome sequencing (WES) was conducted to identify the types and locations of possible gene mutations. Neurological development was assessed using electroencephalography (EEG), magnetic resonance imaging (MRI) and Gesell developmental evaluation.
UNASSIGNED: All four CFCS patients exhibited de novo BRAF gene mutations, manifesting with cardiac malformations, distinctive facial features, skin and hair changes, and neurological abnormalities. WES revealed that the specific BRAF mutations were closely linked to their clinical severity. Three patients displayed milder symptoms (case 1-3, genotype I or II), demonstrating stability or slight improvement, whereas one patient (case 4, genotype III) suffered from a severe phenotype characterized by profound neurological and digestive system impairments, leading to a significantly reduced quality of life and a grim prognosis.
UNASSIGNED: In CFCS patients, severe developmental delay and seizures are predominant neurological features, possibly accompanied by continuous spike-and-wave during sleep (CSWS) and severe sleep disturbances. CFCS generally carries a poor prognosis, underscoring the importance of disease awareness and early genetic testing.