GeneReviews(®)

GeneReviews(®)

Book. 1993

Authors: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K

Abstract
CLINICAL CHARACTERISTICS: Myhre syndrome is a connective tissue disorder with multisystem involvement, progressive and proliferative fibrosis that may occur spontaneously or following trauma or surgery, mild-to-moderate intellectual disability, and in some instances, autistic-like behaviors. Organ systems primarily involved include: cardiovascular (congenital heart defects, long- and short-segment stenosis of the aorta and peripheral arteries, pericardial effusion, constrictive pericarditis, restrictive cardiomyopathy, and hypertension); respiratory (choanal stenosis, laryngotracheal narrowing, obstructive airway disease, or restrictive pulmonary disease), gastrointestinal (pyloric stenosis, duodenal strictures, severe constipation); and skin (thickened particularly on the hands and extensor surfaces). Additional findings include distinctive craniofacial features and skeletal involvement (intrauterine growth restriction, short stature, limited joint range of motion). To date, 55 individuals with molecularly confirmed Myhre syndrome have been reported.
DIAGNOSIS/TESTING: The diagnosis of Myhre syndrome is established by detecting a de novoSMAD4 heterozygous pathogenic variant in a proband with characteristic clinical findings.
MANAGEMENT: Treatment of manifestations: Symptomatic treatment (with attention to limiting tissue trauma by minimizing instrumentation during diagnosis and management) by specialty experts of the following involvement: cardiovascular, respiratory (including tracheostomy when tracheal stenosis is recurrent or complete), and GI; routine management of speech and language delay, intellectual disability, behavioral problems. Prevention of secondary complications: Limiting of tissue trauma given the apparent increased risk for proliferative fibrosis following otherwise uncomplicated endotracheal intubation and surgical procedures. When possible, alternative noninvasive approaches should be pursued during diagnosis and management Surveillance: Cardiovascular: echocardiogram every one to three years in asymptomatic individuals with a normal echocardiogram at the time of initial diagnosis; in individuals with abnormal cardiac findings at the time of diagnosis, more extensive imaging (including possible cardiac MRI) may be considered. Respiratory: oxygen saturation in children with monitoring as needed for symptoms suggestive of restrictive/obstructive pulmonary disease; annual pulmonary function studies in children oldert than age six years if able to cooperate; evaluation of laryngotracheal stenosis based on symptoms. Annual ophthalmology and audiology evaluations. Agents/circumstances to avoid: Smoking; tissue trauma.
GENETIC COUNSELING: Myhre syndrome is inherited in an autosomal dominant manner. All probands with Myhre syndrome reported to date have the disorder as a result of a de novoSMAD4 pathogenic variant. If the SMAD4 pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the risk to sibs is presumed to be slightly greater than that of the general population (though still <1%) because of the theoretic possibility of parental germline mosaicism. To date, individuals with Myhre syndrome are not known to reproduce and fertility has not been assessed. Once the SMAD4 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at theoretic increased risk for Myhre syndrome and preimplantation genetic diagnosis are possible.

PMID: 28406602

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