Alhalak Rouzy, Al-Haideri Mohammed H, Khan Arif
Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, ARE.
Pediatric Neurology, Neuropedia Hospital, Dubai, ARE.
Cureus. 2023 Feb 15;15(2):e35021. doi: 10.7759/cureus.35021. eCollection 2023 Feb.
Cardiofaciocutaneous syndrome is a rare, sporadic disease caused by germline mutations in the Ras/MAPK (mitogen-activated protein kinase) pathway. Patients usually present with craniofacial anomalies, cardiac defects, and neurocutaneous abnormalities. The features of cardiofaciocutaneous syndrome overlap with two other syndromes known as Noonan's syndrome and Costello's syndrome. Similarly, those two syndromes are caused by mutations in the Ras/MAPK pathway. The diagnosis of cardiofaciocutaneous syndrome is suspected based on the clinical presentation and confirmed by genetic analysis. We report a case of a seven-month-old boy who presented with complaints of developmental delay, poor weight gain, and seizures. Physical examination revealed several dysmorphic features, including coarse facies, long philtrum, thin upper lip, a broad forehead, and long toes. Neurological examination showed hypotonia in all four limbs, with normal power and reflexes. However, the infant did not have any remarkable cutaneous abnormalities. Whole-exome sequencing picked up a gene mutation, and the patient was diagnosed with cardiofaciocutaneous syndrome. On follow-up, the patient developed findings suggestive of autoimmune hepatitis. Cardiofaciocutaneous syndrome remains a challenging diagnosis that requires a detailed assessment of the patient, as well as qualified centers with genetic analysis for diagnosis confirmation. Management of cardiofaciocutaneous patients requires a multidisciplinary team approach in order to improve the outcomes. Further exploration is required into atypical presentations of the disease as well as autoimmune disease associated with RASopathies.
心脏颜面皮肤综合征是一种由Ras/丝裂原活化蛋白激酶（MAPK）通路中的种系突变引起的罕见散发性疾病。患者通常表现为颅面畸形、心脏缺陷和神经皮肤异常。心脏颜面皮肤综合征的特征与另外两种综合征——努南综合征和科斯特洛综合征重叠。同样，这两种综合征也是由Ras/MAPK通路中的突变引起的。心脏颜面皮肤综合征的诊断基于临床表现怀疑，并通过基因分析确诊。我们报告一例7个月大男孩，其主诉为发育迟缓、体重增加不佳和癫痫发作。体格检查发现了一些畸形特征，包括面容粗糙、人中长、上唇薄、额头宽和脚趾长。神经学检查显示四肢肌张力低下，肌力和反射正常。然而，该婴儿没有任何明显的皮肤异常。全外显子测序发现了一个基因突变，该患者被诊断为心脏颜面皮肤综合征。随访中，患者出现了提示自身免疫性肝炎的表现。心脏颜面皮肤综合征仍然是一个具有挑战性的诊断，需要对患者进行详细评估，以及具备基因分析能力的合格中心来确诊。心脏颜面皮肤综合征患者的管理需要多学科团队方法以改善治疗结果。需要进一步探索该疾病的非典型表现以及与RAS病相关的自身免疫性疾病。
