RESUMEN
Myhre syndrome is a rare, distinctive syndrome due to specific gain-of-function mutations in SMAD4. The characteristic phenotype includes short stature, dysmorphic facial features, hearing loss, laryngotracheal anomalies, arthropathy, radiographic defects, intellectual disability, and a more recently appreciated spectrum of cardiovascular defects with a striking fibroproliferative response to surgical intervention. We report four newly described patients with typical features of Myhre syndrome who had (i) a mildly narrow descending aorta and restrictive cardiomyopathy; (ii) recurrent pericardial and pleural effusions; (iii) a large persistent ductus arteriosus with juxtaductal aortic coarctation; and (iv) restrictive pericardial disease requiring pericardiectomy. Additional information is provided about a fifth previously reported patient with fatal pericardial disease. A literature review of the cardiovascular features of Myhre syndrome was performed on 54 total patients, all with a SMAD4 mutation. Seventy percent had a cardiovascular abnormality including congenital heart defects (63%), pericardial disease (17%), restrictive cardiomyopathy (9%), and systemic hypertension (15%). Pericarditis and restrictive cardiomyopathy are associated with high mortality (three patients each among 10 deaths); one patient with restrictive cardiomyopathy also had epicarditis. Cardiomyopathy and pericardial abnormalities distinguish Myhre syndrome from other disorders caused by mutations in the TGF-ß signaling cascade (Marfan, Loeys-Dietz, or Shprintzen-Goldberg syndromes). We hypothesize that the expanded spectrum of cardiovascular abnormalities relates to the ability of the SMAD4 protein to integrate diverse signaling pathways, including canonical TGF-ß, BMP, and Activin signaling. The co-occurrence of congenital and acquired phenotypes demonstrates that the gene product of SMAD4 is required for both developmental and postnatal cardiovascular homeostasis. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Anomalías Cardiovasculares/diagnóstico , Anomalías Cardiovasculares/genética , Criptorquidismo/diagnóstico , Criptorquidismo/genética , Trastornos del Crecimiento/diagnóstico , Trastornos del Crecimiento/genética , Deformidades Congénitas de la Mano/diagnóstico , Deformidades Congénitas de la Mano/genética , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Mutación , Fenotipo , Proteína Smad4/genética , Adolescente , Adulto , Anomalías Cardiovasculares/terapia , Niño , Criptorquidismo/terapia , Ecocardiografía , Exones , Facies , Femenino , Estudios de Asociación Genética , Trastornos del Crecimiento/terapia , Deformidades Congénitas de la Mano/terapia , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Hibridación Fluorescente in Situ , Discapacidad Intelectual/terapia , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Ultrasonografía , Adulto JovenRESUMEN
This study assessed attitudes and beliefs regarding the importance of a genetic versus non-genetic diagnosis within the mitochondrial disease community. Survey respondents were categorized into two groups - those with a genetic diagnosis, and those with a non-genetic diagnosis of mitochondrial disease. We found that while both groups perceive problems with the support available to adult mitochondrial disease patients, the non-genetic group experiences less medical and social support due to lack of a definitive diagnosis. Understanding the efficacy of existing resources for mitochondrial disease sub-groups will allow for the development or improvement of resources designed to meet patient needs.