Familial cases of atypical clinical features genetically diagnosed as LEOPARD syndrome (multiple lentigines syndrome)

Summary Five familial cases exhibited ephelides‐like multiple lentigines, and we examined three of them, a mother and two sons. All three patients presented with small dark‐brown maculae on the face and neck and electrocardiographic abnormalities. These findings sufficed to fulfill the criteria for LEOPARD syndrome (multiple lentigines syndrome), although they lacked five of seven major clinical features. However, the family members presented with a webbed neck and pectus excavatum, which are more frequently seen in Turner or Noonan syndrome. Histological examination of the lentigines revealed slightly elongated rete ridges, a hyperpigmented basal layer, and melanophages in the papillary dermis. Direct sequencing of the patients’ genomic DNA revealed that all three had a consistent missense mutation [c.1403C > T (p.T468M)] in the PTPN11 gene, confirming LEOPARD syndrome with an atypical phenotype. It was suggested that LEOPARD syndrome shows a diverse phenotype but its diagnosis can be verified by mutation analysis.