LEOPARD syndrome- 2

Overview

LEOPARD syndrome is a rare autosomal dominant, multisystem disease caused by a mutation in the protein tyrosine phosphatase, non-receptor type 11 gene (PTPN11). The disease is a complex of features, mostly involving the skin, skeletal and cardiovascular systems, they may or may not be present in all patients. The nature of how the mutation causes each of the condition's symptoms is not well known, however research is ongoing. Related to Noonan syndrome, LEOPARD syndrome is caused by a different missense mutation of the same gene. LEOPARD syndrome may also be called multiple lentigines syndrome, cardiomyopathic lentiginosis, Gorlin's syndrome II, Capute-Rimoin-Konigsmark-Esterly-Richardson syndrome, or Moynahan syndrome. Noonan syndrome is fairly common (1:1000 to 1:2500 live births), and neurofibromatosis 1 (which was once thought to be related to LEOPARD syndrome) is also common (1:3500), but however no epidemiologic data exists for LEOPARD syndrome.

Symptoms

  • Lentigines (multiple)
  • Electrocardiographic conduction abnormalities
  • Ocular hypertelorism
  • Pulmonary stenosis
  • Abnormalities of genitalia
  • Retardation of growth
  • Deafness

Causes

Familial cases suggest an autosomal dominant mode of inheritance with variable expressivity. Speculation exists on the more severe course of the disease in males, which may partially explain the slight preponderance of men in the large collected series of Voron et al in 1976.9

Diagnosis

The diagnosis of LS is made on clinical grounds, by observation of key features. PTPN11 and RAF1 are the only genes known to be associated with LS. Molecular genetic testing of the two genes identifies mutations in about 93% of affected individuals. At least one additional causative gene is likely to exist.