title: Natural history and life-threatening complications in Myhre syndrome and review of the literature.
abstract: Myhre syndrome (OMIM 139210) is a rare developmental disorder inherited as an autosomal dominant trait and caused by a narrow spectrum of missense mutations in the SMAD4 gene. The condition features characteristic face, short stature, skeletal anomalies, muscle pseudohypertrophy, restricted joint mobility, stiff and thick skin, and variable intellectual disability. While most of the clinical features manifest during childhood, the diagnosis may be challenging during the first years of life. We report on the evolution of the clinical features of Myhre syndrome during childhood in a subject with molecularly confirmed diagnosis. The clinical records of 48 affected patients were retrospectively analysed to identify any early clinical signs characterizing this disorder and to better delineate its natural history. We also note that pericarditis and laryngotracheal involvement represent important life-threatening complications of Myhre syndrome that justify the recommendation for cardiological and ENT follow-up for these patients.
  
  
  CONCLUSIONS
  Short length/stature, short palpebral fissures, and brachydactyly with hyperconvex nails represent signs/features that might lead to the correct diagnosis in the first years of life and direct to the proper molecular analysis. We underline the clinical relevance of pericarditis and laryngotracheal stenosis as life-threatening complications of this disorder and the need for careful monitoring, in relation to their severity.
  
  
  BACKGROUND
  • The clinical and radiological signs of the disease in children older than 7-8 years. • Pericarditis, sometimes occurring with constrictive pericardium requiring pericardiectomy, has been reported as a recurrent feature but has not been adequately stressed in previous literature. What is New: • Short length/stature, short palpebral fissures, brachydactyly with hyperconvex nails represent clinical signs that might lead to diagnosis in the first years of life. • Review of the literature showed that pericarditis and laryngotracheal complications represent major recurrent issues in patients with Myhre syndrome.
authors: Clinical Genetics Unit, Department of Obstetrics and Paediatrics, IRCCS, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. garavelli.livia@asmn.re.it.
authors: Livia
authors: L
authors: Garavelli
authors: Clinical Genetics Unit, Department of Obstetrics and Paediatrics, IRCCS, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
authors: Ilenia
authors: I
authors: Maini
authors: Clinical Genetics Unit, Department of Obstetrics and Paediatrics, IRCCS, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
authors: Federica
authors: F
authors: Baccilieri
authors: Clinical Genetics Unit, Department of Obstetrics and Paediatrics, IRCCS, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.|Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors: Ivan
authors: I
authors: Ivanovski
authors: Clinical Genetics Unit, Department of Obstetrics and Paediatrics, IRCCS, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
authors: Marzia
authors: M
authors: Pollazzon
authors: Clinical Genetics Unit, Department of Obstetrics and Paediatrics, IRCCS, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
authors: Simonetta
authors: S
authors: Rosato
authors: Department of Medical and Surgical Sciences of Childhood and Adult, University of Modena and Reggio Emilia, Modena, Italy.
authors: Lorenzo
authors: L
authors: Iughetti
authors: Medical Genetics Service, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Sheila
authors: S
authors: Unger
authors: Department of Paediatrics, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
authors: Andrea
authors: A
authors: Superti-Furga
authors: Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors: Marco
authors: M
authors: Tartaglia
mesh_terms: D059327:Brachydactyly; D002648:Child; D003456:Cryptorchidism / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D019066:Facies; D005385:Fingers / Q000002:abnormalities / Q000000981:diagnostic imaging; D006130:Growth Disorders / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D006228:Hand Deformities, Congenital / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D009264:Nails, Malformed / Q000503:physiopathology; D010493:Pericarditis / Q000209:etiology; D010641:Phenotype; D011859:Radiography; D012189:Retrospective Studies; D051901:Smad4 Protein / Q000235:genetics*
chemical_list: C497796:SMAD4 protein, human; D051901:Smad4 Protein
keywords: Cardiac tamponade; Laryngotracheal stenosis; Myhre syndrome; Pericarditis