Demir Şenol, Alavanda Ceren, Yeşil Gözde, Aslanger Ayça Dilruba, Ateş Esra Arslan
Department of Medical Genetics, School of Medicine, Marmara University, Istanbul, Turkey.
Department of Medical Genetics, School of Medicine, Istanbul University, Istanbul, Turkey.
Mol Syndromol. 2023 Apr;14(2):175-180. doi: 10.1159/000527149. Epub 2023 Jan 13.
Myhre syndrome (MS; OMIM #139210) is a rare connective tissue disorder presenting with cardiovascular, respiratory, gastrointestinal, and skeletal system findings. Fewer than 100 patients were reported until recently, and all molecularly confirmed cases had de novo heterozygous gain-of-function mutations in the gene. Dysregulation of the TGF-beta signaling pathway leads to axial and appendicular skeleton, connective tissue, cardiovascular system, and central nervous system abnormalities.
Two siblings, 12 and 9 years old, were referred to us because of intellectual disability, neurodevelopmental delay, and dysmorphic facial features. Physical examination revealed hypertelorism, strabismus, small mouth, prognathism, short neck, stiff skin, and brachydactyly.
With a clinical diagnosis of MS, the gene was analyzed via Sanger sequencing, and a heterozygous c.1486C>T (p.Arg496Cys) pathogenic variation was detected in both of the siblings. The segregation analysis revealed that the mutation was inherited from the father who displayed a milder phenotype. Among the 90 patients in the literature, one family was reported in which two siblings carried the same variation (p.Arg496Cys), inherited from the severely affected mother. We are reporting the second family which has three affected family members, a father and two children. We report this study to remind the clinicians to be aware of the parental transmission of variations and also evaluate the parents of the Myhre cases.
Myhre综合征（MS；OMIM #139210）是一种罕见的结缔组织疾病，伴有心血管、呼吸、胃肠和骨骼系统表现。直到最近，报告的患者不足100例，所有经分子确诊的病例在该基因中都有新生杂合功能获得性突变。TGF-β信号通路失调导致轴性和附肢骨骼、结缔组织、心血管系统和中枢神经系统异常。
两名分别为12岁和9岁的兄弟姐妹因智力残疾、神经发育迟缓及面部畸形特征被转诊至我们处。体格检查发现眼距增宽、斜视、小嘴、下颌前突、短颈、皮肤僵硬和短指。
临床诊断为MS后，通过Sanger测序对该基因进行分析，在两名兄弟姐妹中均检测到杂合的c.1486C>T（p.Arg496Cys）致病性变异。分离分析显示该突变遗传自表现出较轻表型的父亲。在文献报道的90例患者中，有一个家庭报告两名兄弟姐妹携带相同变异（p.Arg496Cys），遗传自受严重影响的母亲。我们报告的是第二个有三名受影响家庭成员（一名父亲和两个孩子）的家庭。我们报告这项研究是为提醒临床医生注意该基因变异的亲代传递情况，并对Myhre综合征病例的父母进行评估。
