Posthumously Diagnosed Myhre Syndrome Presenting With Pleural Remodeling and Endometrial Cancer

Myhre syndrome (OMIM 139210) is a genetic condition defined by neurodevelopmental disability, characteristic facial features, and multisystem proliferative fibrosis. While various types of lung disease have been reported, pleural remodeling leading to restrictive lung disease has not yet been described. There is also a possible increased risk of malignancy, although this is difficult to confirm given the rarity of the condition. A 43-year-old woman with short stature, intellectual disability, recent unintentional weight loss, and a uterine mass was admitted to the intensive care unit for respiratory failure. She had pleural effusions and the lungs did not expand following thoracentesis, consistent with a trapped lung. A uterine mass was also identified that was likely endometrioid carcinoma. In light of this, it was suspected that her lung disease was due to metastatic disease; however, pleural fluid studies did not show evidence of malignancy. Following her death, exome sequencing resulted and identified a pathogenic variant on SMAD4 (NM_005359.5:c.1498A>G (p.Ile500Val)), consistent with a diagnosis of Myhre syndrome. In retrospect, her lung disease was thought to be related to fibrothorax as a complication of Myhre syndrome. This case illustrates the breadth of fibrotic disease that can occur in individuals with Myhre syndrome by describing the first reported case of pleural remodeling leading to fibrothorax. Additionally, our patient's diagnosis of endometrial cancer strengthens the evidence for the proposed increased risk of malignancy in Myhre syndrome.