Myhre syndrome: A first familial recurrence and broadening of the phenotypic spectrum

Ilse Meerschaut, Aude Beyens, Wouter Steyaert, Riet De Rycke, Katrien Bonte, Tine De Backer, Sandra Janssens, Joseph Panzer, Frank Plasschaert, Daniel De Wolf, Bert Callewaert

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


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 SMAD4, 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 SMAD4. 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.

Original languageEnglish
Pages (from-to)2494-2499
Number of pages6
JournalAmerican Journal of Medical Genetics Part A
Issue number12
Publication statusPublished - Dec 2019


  • (assisted) reproduction
  • elastinopathy
  • Myhre syndrome
  • phenotypic spectrum
  • TEM imaging


Dive into the research topics of 'Myhre syndrome: A first familial recurrence and broadening of the phenotypic spectrum'. Together they form a unique fingerprint.

Cite this