Inguinal lymph nodes agenesia in a patient with Schimmelpenning-Feuerstein-Mims syndrome with proven somatic KRAS mutation

Abstract

[Abstract] Schimmelpenning-Feuerstein-Mims (SFM) syndrome is a neurocutaneous disorder that can affect many body systems. The principal and most characteristic anomalies are craniofacial naevus sebaceous in association with neurological, ocular and skeletal findings. The presence of vascular malformations in this condition is unusual; nevertheless, vascular malformations have been suggested by many authors to be part of the spectrum of the same disease. Few cases have been published on the association of SFM with lymphatic malformations. This syndrome is categorized as a mosaic RASopathy due to postzygotic mutations in the HRAS, KRAS or NRAS genes. These genes are involved in the RAF-MEK-ERK signalling pathway, which is activated by mutant cells, increasing cellular proliferation. These mutations have been found only in naevus sebaceous cells, and may be also the explanation for many of the associated pathologies. We report a case of an 18-year-old boy diagnosed with SFM syndrome associated with lymphatic malformation in the legs and agenesia of the inguinal lymph nodes. The lymphatic alterations were diagnosed by gammography of the legs. The genetic diagnosis was confirmed by the presence of a KRAS postzygotic mutation in naevus sebaceous cells of a skin specimen. Genetically confirmed cases of mosaic RASopathies should be used to more accurately characterize phenotypic presentations of this syndrome and develop a future therapeutic strategy, such as molecular targeted therapy.