Myhre syndrome: A first familial recurrence and broadening of the phenotypic spectrum
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- Ilse Meerschaut
- Center for Medical Genetics Ghent University Hospital Ghent Belgium
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- Aude Beyens
- Center for Medical Genetics Ghent University Hospital Ghent Belgium
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- Wouter Steyaert
- Center for Medical Genetics Ghent University Hospital Ghent Belgium
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- Riet De Rycke
- Department of Biomedical Molecular Biology Ghent University Ghent Belgium
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- Katrien Bonte
- Department of Head, Neck and Maxillofacial Surgery Ghent University Hospital Ghent Belgium
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- Tine De Backer
- Department of Cardiology Ghent University Hospital Ghent Belgium
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- Sandra Janssens
- Center for Medical Genetics Ghent University Hospital Ghent Belgium
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- Joseph Panzer
- Department of Pediatric Cardiology Ghent University Hospital Ghent Belgium
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- Frank Plasschaert
- Department of Orthopedic Surgery Ghent University Hospital Ghent Belgium
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- Daniël De Wolf
- Department of Pediatric Cardiology Ghent University Hospital Ghent Belgium
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- Bert Callewaert
- Center for Medical Genetics Ghent University Hospital Ghent Belgium
説明
<jats:title>Abstract</jats:title><jats:p>Myhre syndrome is a rare multisystem connective tissue disorder, characterized by short stature, facial dysmorphology, variable intellectual disability, skeletal abnormalities, arthropathy, cardiopathy, laryngotracheal anomalies, and stiff skin. So far, all molecularly confirmed cases harbored a de novo heterozygous gain‐of‐function mutation in <jats:italic>SMAD4</jats:italic>, encoding the SMAD4 transducer protein required for both transforming growth factor‐beta and bone morphogenic proteins signaling. We report on four novel patients (one female proband and her two affected children, and one male proband) with Myhre syndrome harboring the recurrent c.1486C>T (p.Arg496Cys) mutation in <jats:italic>SMAD4</jats:italic>. The female proband presented with a congenital heart defect, vertebral anomalies, and facial dysmorphic features. She developed severe tracheal stenosis requiring a total laryngectomy. With assisted reproductive treatment, she gave birth to two affected children. The second proband presented with visual impairment following lensectomy in childhood, short stature, brachydactyly, stiff skin, and decreased peripheral sensitivity. Transmission electron microscopy (TEM) of the dermis shows irregular elastin cores with globular deposits and almost absent surrounding microfibrils and suggests age‐related increased collagen deposition. We report on the first familial case of Myhre syndrome and illustrate the variable clinical spectrum of the disorder. Despite the primarily fibrotic nature of the disease, TEM analysis mainly indicates elastic fiber anomalies.</jats:p>
収録刊行物
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- American Journal of Medical Genetics Part A
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American Journal of Medical Genetics Part A 179 (12), 2494-2499, 2019-10-09
Wiley