Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

LEOPARD Syndrome [L81.4]

OMIM numbers: 151100, 176876 (PTPN11), 611554, 164760 (RAF1), 613707, 164757 (BRAF)

Dr. rer. biol. hum. S. Chahrokh-Zadeh, Dr. rer. nat. Karin Mayer

Scientific Background

The LEOPARD syndrome, also known as cardiomyopathic lentiginosis, is a rare autosomal dominant disease, which was described for the first time by Gorlin in 1969. LEOPARD is an acronym for the characteristic clinical signs and symptoms

  • multiple lentigines
  • electrocardiographic anomalies
  • ocular hypertelorism
  • pulmonary stenosis
  • abnormal genitalia
  • retardation of growth
  • deafness

In 2002, mutations in the PTPN11 gene were identified as the molecular cause, just like in the partially clinically overlapping Noonan syndrome. In approximately 90% of all LS patients mutations in the PTPN11 gene can be detected which exclusively lead to the substitution of amino acids. In contrast to the Noonan syndrome, there are recurring specific PTPN11 amino acid substitutions, which result in the loss of catalytic activity of the nonreceptor protein tyrosine phosphatase SHP-2. So far, mutations have been identified in the proto-oncogenes RAF1 and BRAF in < 5% of all LS patients. In less than 5% of all patients, no genetic cause has been found so far. However, mutations in other genes of the RAS-ERK-MAP kinase signal transduction are suspected.