Leopard syndromeQ87.1

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.

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