Myocardial fat overgrowth in Proteus syndrome

Abstract

Proteus syndrome is a rare, mosaic disorder with asymmetric and distorting overgrowth of the skeletal system, skin, and adipose tissues. Cardiac abnormalities are rare in this syndrome and only two prior cases have been reported. Many patients with PS followed at our institution underwent transthoracic echocardiograms for preoperative evaluation or as work-up for associated pulmonary disease. Some were noted to have prominent, focal echodense areas in the myocardium. We further investigated cardiac findings in a cohort of children and adult patients with PS. Patients with abnormal echocardiograms were referred for cardiac magnetic resonance imaging, Holter monitoring, and exercise treadmill testing. Twenty children and adults with PS, age 24 months to 50 years old, underwent transthoracic echocardiograms. Seven patients (35%) had focal bright echodense areas within the myocardium suggesting fatty infiltration. The majority of patients had significant involvement of the interventricular septum. The cardiac characteristics of all patients with fatty infiltration on transthoracic echocardiograms were compared to Proteus patients without these findings. There were no significant differences in chamber sizes, mass, systolic or diastolic function. No increased risk of conduction defects or arrhythmias was found. This study shows that abnormal fat overgrowth is a common finding in the myocardium in patients with Proteus syndrome; however, it is not associated with functional derangements or arrhythmias. Further evaluation of a larger number of Proteus patients is needed in order to determine the frequency and prognosis of cardiac involvement.

Cardiothoracic imaging findings of Proteus syndrome

“…Informed consent was obtained from all the participants or their parents/legal guardian for minors (under the age of 18). A subset of the current study population was previously reported by Hannoush et al and Jamis-Dow et al 17 , 18 .…”

“…All chest CT studies were evaluated on a PACS workstation (CareStream, Version 12.1.6.1005, Carestream Health, NY) independently by two readers who were fellowship-trained in thoracic and body imaging and who were aware of the Proteus syndrome diagnosis but were blinded to all other clinical information. The readers (A.S., 10 years of experience and E.B.T., 13 years of experience) evaluated the lungs, heart, pleura, thoracic vasculature, chest wall and mediastinum for cardiothoracic imaging findings that were previously reported in the literature (Supplemental Table S2 ) 7 , 12 , 14 – 18 , 21 – 23 . The entire thorax was assessed for the presence of nodules or masses suspicious for malignancy 8 , 17 and any other additional thoracic findings.…”

“…Although the cardiothoracic radiological manifestations of Proteus syndrome have been described in previous clinical reports 12 – 15 and small clinical series 16 – 18 , to our knowledge, a comprehensive study systematically examining cardiothoracic imaging findings in a large series of individuals has not been reported. Our aim was to systematically evaluate the cardiothoracic imaging manifestations of Proteus syndrome in a large cohort of individuals to better determine their prevalence.…”

Molecular heterogeneity of the cerebriform connective tissue nevus in mosaic overgrowth syndromes

“…Given that the denominator for PROS is larger, this suggests (but does not prove) that the risk of tumors is much higher in Proteus than in PROS. Further, we are not aware of myocardial fat overgrowth in individuals with PROS, whereas this is common in Proteus syndrome (Hannoush et al 2015). Other generalizations could be enumerated, but the point is that although both Proteus syndrome and PROS can display a wide range of severity, the nature and frequency of specific manifestations are distinct in the two syndromes.…”

Proteus syndrome caused by novel somatic AKT1 duplication

“…The skin, bones, and adipose tissue are commonly affected. 2 The syndrome is a mosaic genetic syndrome that occurs de novo, with an estimated prevalence of less than one per one million. 3 Proteus syndrome can be associated with bony defects, epidermal nevi, vascular tissue malformations, adipose tissue dyregulation, and lungs abnormalities.…”