Leopard syndrome: the potential cardiac defect underlying skin phenotypes

Abstract LEOPARD syndrome (OMIM #151,100) caused by a germline PTPN11 mutation are characterized as multisystemic anomalies and variable marked phenotypes such as multiple lentigines and cafe´-au-lait spots, electrocardiographic conduction abnormalities, ocular hypertelorism/obstructive cardiomyopathy, pulmonary stenosis, abnormal genitalia, retardation of growth, and deafness. Phenotype overlap complicates clinical discrimination within RASopathies, making the diagnosis of LEOPARD more confusing and challenging. Besides, LEOPARD patients do not usually present with all these typical clinical features, increasing the possibility of underdiagnosis or misdiagnosis. Herein, we report a case of LEOPARD syndrome in a patient who only presented with pigmented skin spots and was initially diagnosed with multiple acquired melanocytic nevi. Subsequent pathological examination confirmed the diagnosis of multiple lentigines rather than melanocytic nevi. A genetic study showed a germline PTPN11 (Tyr279Cys) mutation and raised the suspicion of LEOPARD syndrome. A subsequent ECG examination detected potential cardiac defects and confirmed the diagnosis of LEOPARD. We considered that the potential damage of other systems underlying the skin multiple lentigines should not be ignored. The diagnosis of LEOPARD syndrome in an early stage before cardiac damage has reached a serious and irreversible stage can be meaningful for patients to fully understand the potential risks, complications and prognosis of the disease and to take appropriate precautions to prevent the potential risk of cardiac damage