Despite a change in formal name, the 'LEOPARD' acronym is still useful to summarize the clinical features:
- L: lentigines (multiple)
- E: ECG conduction abnormalities
- O: ocular hypertelorism
- P: pulmonary stenosis
- A: abnormal genitals
- R: retardation of growth
- D: deafness (sensorineural)
Importantly, this acronym does not include the other craniofacial anomalies (in addition to hypertelorism) which are identical to those of Noonan syndrome and present in nearly all patients 5.
Thought to result from a mutation in the PTPN11 (protein tyrosinephosphatase nonreceptor type 11) gene located on chromosome 12q24.1 2, which results in increased signaling of the Ras/MAPK pathway. Thus, the disorder is classified as a RASopathy 5.
One concerning potential complication is the development of hypertrophic cardiomyopathy (HCM) (often in infancy) related to congenital cardiac defects.
History and etymology
Originally described by R J Gorlin and his colleagues in 1969 1.
- 1. Gorlin RJ, Anderson RC, Blaw M. Multiple lentigenes syndrome. Am. J. Dis. Child. 1969;117 (6): 652-62. doi:10.1001/archpedi.1969.02100030654006 - Pubmed citation
- 2. Hagspiel KD, Candinas RC, Hagspiel HJ et-al. LEOPARD syndrome: cardiac imaging findings. AJR Am J Roentgenol. 2005;184 (3): S21-4. AJR Am J Roentgenol (full text) - Pubmed citation
- 3. Lodish MB, Stratakis CA. The differential diagnosis of familial lentiginosis syndromes. 2011;doi:10.1007/s10689-011-9446-x - Pubmed citation
- 4. Renker M, Schoepf UJ, Hlavacek AM. Coronary artery dilation in LEOPARD syndrome: surveillance with low radiation dose cardiac CT. Heart. 2010;96 (17): 1429. doi:10.1136/hrt.2010.202572 - Pubmed citation
- 5. Rauen KA. The RASopathies. Annual review of genomics and human genetics. 14: 355-69. doi:10.1146/annurev-genom-091212-153523 - Pubmed