title: Myhre syndrome: Clinical features and restrictive cardiopulmonary complications.
abstract: Myhre syndrome, a connective tissue disorder characterized by deafness, restricted joint movement, compact body habitus, and distinctive craniofacial and skeletal features, is caused by heterozygous mutations in SMAD4. Cardiac manifestations reported to date have included patent ductus arteriosus, septal defects, aortic coarctation and pericarditis. We present five previously unreported patients with Myhre syndrome. Despite varied clinical phenotypes all had significant cardiac and/or pulmonary pathology and abnormal wound healing. Included herein is the first report of cardiac transplantation in patients with Myhre syndrome. A progressive and markedly abnormal fibroproliferative response to surgical intervention is a newly delineated complication that occurred in all patients and contributes to our understanding of the natural history of this disorder. We recommend routine cardiopulmonary surveillance for patients with Myhre syndrome. Surgical intervention should be approached with extreme caution and with as little invasion as possible as the propensity to develop fibrosis/scar tissue is dramatic and can cause significant morbidity and mortality.
authors.affiliation: Division of Clinical Genetics, University of Nebraska Medical Center, Munroe-Meyer Institute for Genetics and Rehabilitation, Omaha, Nebraska.|University of Nebraska Medical Center, Munroe-Meyer Institute for Genetics and Rehabilitation, Human Genetics Laboratory, Omaha, Nebraska.
authors.forename: Lois J
authors.initials: LJ
authors.lastname: Starr
authors.affiliation: Department of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Grange
authors.affiliation: Division of Cardiology, Children's Hospital and Medical Center, Omaha, Nebraska.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Delaney
authors.affiliation: Division of Cardiology, Children's Hospital and Medical Center, Omaha, Nebraska.
authors.forename: Anji T
authors.initials: AT
authors.lastname: Yetman
authors.affiliation: Division of Cardiac Surgery, Children's Hospital and Medical Center, Omaha, Nebraska.
authors.forename: James M
authors.initials: JM
authors.lastname: Hammel
authors.affiliation: University of Nebraska Medical Center, Munroe-Meyer Institute for Genetics and Rehabilitation, Human Genetics Laboratory, Omaha, Nebraska.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Sanmann
authors.affiliation: Division of Pediatric Pathology, Children's Hospital and Medical Center, Omaha, Nebraska.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Perry
authors.affiliation: Division of Medical Genetics, Arkansas Children's Hospital, Little Rock, Arkansas.
authors.forename: G Bradley
authors.initials: GB
authors.lastname: Schaefer
authors.affiliation: Division of Clinical Genetics, University of Nebraska Medical Center, Munroe-Meyer Institute for Genetics and Rehabilitation, Omaha, Nebraska.
authors.forename: Ann Haskins
authors.initials: AH
authors.lastname: Olney
mesh_terms: D002648:Child; D003456:Cryptorchidism / Q000150:complications / Q000209:etiology* / Q000628:therapy*; D004562:Electrocardiography; D019066:Facies; D005260:Female; D006130:Growth Disorders / Q000150:complications / Q000209:etiology* / Q000628:therapy*; D006228:Hand Deformities, Congenital / Q000150:complications / Q000209:etiology* / Q000628:therapy*; D006331:Heart Diseases / Q000601:surgery*; D016027:Heart Transplantation; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000209:etiology* / Q000628:therapy*; D008297:Male; D009154:Mutation; D011247:Pregnancy; D051901:Smad4 Protein / Q000235:genetics; D055815:Young Adult
chemical_list: C497796:SMAD4 protein, human; D051901:Smad4 Protein
keywords: Myhre syndrome; SMAD4; TGFβ; connective tissue disorder; restrictive cardiomyopathy