Leopard syndrome Q87.1

Acronym for a clinical constellation of the individual symptoms

• Lentiginosis
• electrocardiographic disturbances
• ocular hypertelorism
• pulmonary stenosis
• abnormalities of the genitals
• retardation of growth
• deafness.

Multiple lentigines are always present, associated with various internal changes. See also Lentiginosis.

LEOPARD syndrome/Noonan syndrome belongs to the family of familial lentiginosis syndromes. This further includes the following syndromes:

• Peutz-Jeghers syndrome
• Carney syndrome
• PTEN-Hamartoma syndrome
• LEOPARD syndrome/Noonan syndrome

Autosomal-dominant inheritance, variable expressivity, variable penetrance. Mutations of the PTPN11 gene (gene locus: 12q24.1) have been described. Pathogenetically, the possibility of a neuroectodermal disorder with pleiotropic effect on tissues of mesodermal origin is discussed.

Mutations in the PTPN11 gene are also described in Noonan syndrome. PTPN11 is an oncogene. Its gene product SHP-2 plays a role in embryonic development of heart, blood cells and bone. In cases where a PTPN11 mutation cannot be detected, mutations of RAF1 (3%) may be present.

See also RASopathies.

Integument: Pronounced lentiginosis with 2-8 mm brownish spots in very dense seeding on the trunk and in lesser distribution on the rest of the body.

Extracutaneous manifestations: ECG changes (conduction disturbances with thigh block, nonspecific disturbance of excitation propagation). Ocular hypertelorism, rarely other craniofacial malformations; valvular pulmonary stenosis, sometimes combined with aortic stenosis; genital abnormalities such as bilateral cryptorchidism, furthermore hypoplasia of the genitals with hypospadias in males, hypoplastic ovaries in females; retardation of growth with short stature; sensorineural sensorineural hearing loss or deafness.

1. Bezniakow N et al (2014) The RASopathies as an example of RAS/MAPK pathway disturbances - clinical presentation and molecular pathogenesis of selected syndromes. Dev Period Med 18:285-296
2. Capute AJ, Rimoin DL, Konigsmark BW et al (1969) Congenital deafness and multiple lentigines. Arch Derm 100: 207-213
3. Choi WW et al (2003) LEOPARD syndrome with a new association of congenital corneal tumor, choristoma. Pediatric dermatol 20: 158-160
4. Gorlin RJ, Anderson RC, Blaw M (1969) Multiple lentigines syndrome. Complex comprising multiple lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth, sensorineural deafness, and autosomal dominant hereditary pattern. Am J Dis Child 117: 652-662
5. Karbach J et al (2012) Case report: Noonan syndrome with multiple giant cell lesions and review of the literature. Am J Med Genet A 158A: 2283-2289
6. Legius E et al (2002) PTPN11 mutations in LEOPARD syndrome. J Med Genet 39: 571-574
7. Moynahan EJ (1970) Progressive cardiomyopathic lentiginosis: First report of autopsy findings in a recently recognized inheritable disease (autosomal dominant). Proc R Soc Med (London) 63: 448-451
8. Petter G et al (2002) Multiple lentigines (LEOPARD) syndromes. Case reports and review of the Literature. dermatologist 53: 403-408
9. Smpokou P et al (2014) Malignancy in Noonan syndrome and related disorders. Clin Genet 88:516-522
10. Staub J et al (2011) Type 1 of LEOPARD syndrome in a 53-year-old patient. 46th DDG meeting: 10.1111/y. 1610-0387. 2011.07633. DK 01
11. Vehring KH, Kretzschmar L, Hamm H (1991) The LEOPARD syndrome - a generalized lentiginosis with indicator function. Nude Dermatol 17: 85-88
12. Zeisler EP, Becker SW (1936) Generalized lentigo: its relation to systemic nonelevated nevi. Arch Dermatol 33: 109-125