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Molecular syndromology
Apr, 2023;14 (2): 175-180.

A Second Family with Myhre Syndrome Caused by the Same Recurrent Pathogenic Variation (p.Arg496Cys).

Şenol Demir, Ceren Alavanda, Gözde Yeşil, Ayça Dilruba Aslanger, Esra Arslan Ateş
Author Information
  1. Şenol Demir: Department of Medical Genetics, School of Medicine, Marmara University, Istanbul, Turkey.
  2. Ceren Alavanda: Department of Medical Genetics, School of Medicine, Marmara University, Istanbul, Turkey.
  3. Gözde Yeşil: Department of Medical Genetics, School of Medicine, Istanbul University, Istanbul, Turkey.
  4. Ayça Dilruba Aslanger: Department of Medical Genetics, School of Medicine, Istanbul University, Istanbul, Turkey.
  5. Esra Arslan Ateş: Genetic Diseases Diagnostic Center, Marmara University Pendik Training and Research Hospital, İstanbul, Turkey.
PMID: 37064342 DOI: 10.1159/000527149

Abstract

Introduction: 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.
Case Presentation: 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.
Discussion: 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.

Keywords

Fertility Intellectual disability Myhre syndrome SMAD4 gene

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