Anesthesia and LEOPARD Syndrome: A Review of Forty-nine Anesthetic Exposures Tze Yeng Yeoh, MB, ChB,* , † Erica D. Wittwer, MD, PhD,* Toby N. Weingarten, MD,* and Juraj Sprung, MD, PhD* Objectives: LEOPARD syndrome is a rare congenital dis- ease that can manifest with cardiac anomalies, multiple lentigines, ocular hypertelorism, growth retardation, and deafness. The purpose of this case series was to review the most prominent comorbidities associated with LEOPARD syndrome, and describe perioperative outcomes in a series of patients undergoing anesthesia. Design: Retrospective case series review Setting: Tertiary care institution Participants: Patients diagnosed with LEOPARD syn- drome who underwent surgical procedures requiring anes- thesia at this institution. Intervention: The medical and anesthesia records of patients with LEOPARD syndrome were reviewed. Demo- graphic information, clinical features of LEOPARD syndrome, comorbidities, intraoperative and postoperative events and complications were recorded. A systematic literature review also was conducted. Measurements and Main Results: Nine patients with LEOP- ARD syndrome underwent 49 procedures under general anes- thesia (n ¼ 40) or monitored anesthesia care (n ¼ 9). The majority of operations were related to correction of cardiac anomalies (n ¼ 20). The most common cardiac malformations were ventricular septal hypertrophy and pulmonary (or subpul- monary) stenosis, and major perioperative complications were related to severe arrhythmias and/or cardiac decompensation. Conclusions: Dominant pathology associated with perio- perative complications in patients with LEOPARD syndrome is related to cardiac disease. A large proportion of patients with this condition have ventricular septal hypertrophy, which tends to progress with age; therefore, these patients under- going anesthesia should have recent cardiologist evaluation. & 2014 Elsevier Inc. All rights reserved. KEY WORDS: LEOPARD syndrome, ventricular septal hypertrophy, arrhythmia, anesthesia L EOPARD syndrome (LS) is a very rare congenital multi- system disorder characterized by multiple lentigines, electrocardiographic (ECG) conduction abnormalities, ocular hypertelorism, pulmonary valve stenosis (as well as other abnormalities such as hypertrophic cardiomyopathy, aortic stenosis, or mitral valve prolapse), abnormal genitalia, retarded growth, and deafness. Clinical features of LS are listed in Table 1. Although a total of approximately 200 cases of patients with clinical features suggestive of LS have been reported, the prevalence remains unknown. 1 The clinical diagnosis commonly is based on Voron et al’s 2 recommendations, who suggested minimum diagnos- tic criteria: Presence of multiple lentigines and 2 other typical features (cardiac anomalies, ECG abnormalities, genitouri- nary anomalies, endocrine disorders, neurologic defects, typical craniofacial dysmorphism, short stature, skeletal anomalies, and family history) or, in the absence of lenti- gines, 3 typical features of LS and a first-degree relative with LS. 2 However, a definitive clinical diagnosis can be difficult due to overlap of the typical phenotypic characteristics with several genetic diseases such as Noonan syndrome, neuro- fibromatosis type 1, Costello syndrome, and cardiofaciocuta- neous syndrome, especially in young patients who may not yet have developed lentigines. Patients may need to be reevaluated as they grow older for the correct diagnosis. Important characteristics that differentiate LS from other syn- dromes are café-au-lait spots, lentigines, ventricular hyper- trophy, and deafness. 1 LS may occur sporadically but often is inherited as an autosomal dominant trait. 1 The location of the gene mutation was detected in early 2000, and approximately 85% of patients with LS were found to have a missense mutation in the PTPN11 gene on chromosome 12q24.1. 1 Specifically, the majority of mutations occur in exons 7, 12, or 13 of the PTPN11 gene, and this distinguishes LS from Noonan syn- drome, which is caused by different mutations within the same gene. 3,4,5 Other less frequent gene mutations in LS are the RAF1 and BRAF genes. 3 The availability of genetic testing allows confirmation of the clinical diagnosis of LS and its distinction from clinically related syndromes such as Noonan syndrome or neurofibromatosis type 1. Since LS patients have substantial cardiac anomalies and conduction disorders, anesthetic management may be associ- ated with complications. However, because this syndrome is extremely rare, perioperative management and outcomes infre- quently have been reported. The authors aim was to describe the LS-associated comorbidities, to review their implications for perioperative management, and report perioperative out- comes in 9 patients undergoing multiple procedures and surgeries under anesthesia. METHODS This study was approved by the Institutional Review Board (IRB) of Mayo Clinic, Rochester, MN. Consistent with Minnesota Statute 144.335 Subd. 3a. (d), the authors included only patients who had provided authorization for research use of their medical records (historically 495% of patients). 6 A computerized search of the institu- tional medical record databases from January 1, 1980 to December 31, 2010 was conducted to identify all patients with a clinical or genetically confirmed diagnosis of LS. The records of patients with LS were reviewed to select those who had any surgery or procedure under anesthetic care in the authors’ institution. From the *Department of Anesthesiology, Mayo Clinic, Rochester, MN; and †Department of Anaesthesia, National University Hospital, National University Health System, Republic of Singapore. Address reprint requests to Juraj Sprung, MD, PhD, Mayo Clinic, Department of Anesthesiology, 200 First Street SW, Rochester, MN 55905. E-mail: sprung.juraj@mayo.edu © 2014 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2013.09.015 Journal of Cardiothoracic and Vascular Anesthesia, Vol ], No ] (Month), 2014: pp ]]]–]]] 1