Myhre syndrome (MS) is an ultrarare genetic disorder caused by dominant gain-of-function (GOF) mutations in the SMAD4 gene.

[5] Some of these features are life threatening, such as airway or arterial narrowing (laryngotracheal stenosis or aortic coarctation) and fibroproliferation of tissues including lung, heart, and liver.

Changes in SMAD4 binding or availability may result in abnormal signaling in many cell types, which affects development of several body systems and leads to the signs and symptoms of Myhre syndrome.

[11] Because Myhre syndrome is typically caused by a de novo pathogenic variant, most probands represent a simplex case (i.e., a single occurrence in a family).

[11] Rarely, the family history may be consistent with autosomal dominant inheritance (e.g., affected males and females in multiple generations).