LEOPARD Syndrome

LEOPARD Syndrome

This 7-year-old boy was brought in for a routine well-child visit. His history included profound sensorineural hearing loss, (for which he had received cochlear implants) and congenital heart disease (a small ventricular septal defect, subaortic ridge, right ventricular conduction delay, and mild left ventricular dilatation). Both the hearing loss and the cardiac disorders had been diagnosed during the neonatal period. He also had multiple lentigines (present since birth), caf au lait spots, and ocular hypertelorism.

The patient was 44 in tall (below the 3rd percentile). He had a relatively large head compared with his body; head circumference was 54 cm (about the 95th percentile). Pectus deformity was present. Cardiac examination revealed a soft 2/4 holosystolic murmur.

This child has LEOPARD syndrome (also known as multiple lentigines syndrome, cardiocutaneous syndrome, Moynahan syndrome, lentiginosis profusa syndrome, and progressive cardiomyopathic lentiginosis). The acronym LEOPARD stands for multiple Lentigines, ECG abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, growth Retardation, and sensorineural Deafness.1 Other cutaneous (caf au lait spots, schwannomas) and noncutaneous (renal agenesis, absence or duplication of ureter) abnormalities have also been reported.

This condition is transmitted in an autosomal dominant manner with high penetrance and variable expression. Males and females are equally affected. More than 100 cases have been reported since it was first documented in 1935.

Diagnosis requires the presence of multiple lentigines and at least 2 other clinical criteria. If lentigines are absent, the diagnosis requires at least 3 other clinical criteria plus 1 immediate relative with the syndrome.

LEOPARD syndrome has been linked to a mutation in the PTPN11 gene, which is also present in about 40% of patients with Noonan syndrome.2 Despite this association, genetic testing is not necessary for diagnosis. Although Noonan syndrome is characterized by similar abnormalities, such as ocular hypertelorism, cardiac defects (most commonly pulmonary valve stenosis), cryptorchidism, and deafness, it is not associated with lentigines—a hallmark of LEOPARD syndrome.

LEOPARD syndrome should be distinguished from other syndromes associated with generalized lentigines, such as neurofibromatosis (which also presents with caf au lait spots) and Carney complex. The latter is characterized by myxomas, spotty pigmentation, endocrine overreactivity, and psammomatous melanotic schwannomas. The lentigines in Carney complex differ from those in LEOPARD syndrome in that they may also involve the oral mucosa.

Most patients with LEOPARD syndrome lead a normal life. They do need to be assessed periodically with echocardiography and electrocardiography because obstructive cardiomyopathy and cardiac dysrythmias may be a cause of death in select patients.3




1. Jones KL. Multiple lentigines syndrome. Smith’s Recognizable Patterns of Human Malformations. 5th ed. New York: WB Saunders Co; 1997:530-531.

2. Sarkozy A, Obregon MG, Conti E, et al. A novel PTPN11 gene mutation bridges Noonan syndrome, multiple lentigines/LEOPARD syndrome and Noonan-like/multiple giant cell lesion syndrome. Eur J Hum Genet. 2004;12: 1069-1072.

3. Jozwiak S, Schwartz RA, Janniger CK. LEOPARD syndrome (cardiocutaneous lentiginosis syndrome). Cutis. 1996;57:208-214.

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