Von Hippel-Lindau Syndrome

Abstract

Von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome characterized by the development of multiple vascular tumours. The syndrome is caused by inactivation of the VHL protein (pVHL) and increased production of VEGF, PDGF, and TGF-α. The course of VHL syndrome is associated with the development of multiple vascular tumours. Most frequently, these include retinal and central nervous system haemangioblastomas, clear cell renal cell carcinoma, phaeochromocytomas, pancreatic islet tumours, endolymphatic sac tumours, and additionally, renal and pancreatic cystadenomas and epididymal cystadenomas in men. VHL syndrome is a highly complex disease; hence, the diagnosis is often difficult. The diagnosis of any of the characteristic tumours, particularly in children, is an implicit indication for the necessity of diagnosis and genetic tests in the patient and family members and for intensive supervision of carriers of the mutated gene, thereby improving early diagnosis and successful treatment of the malignancies.

An aggressive and expanded phenotype in a kindred with a c.57delG SDHD mutation

“…However, these are known components of other pseudohypoxia syndromes, including the von Hippel-Lindau Syndrome with retinal and spinal cord hemangiomas, the polycythemia-paragangliomasomatostatinoma syndrome with hepatic hemangiomas, and the Maffucci Syndrome with soft tissue hemangiomas (2,12,13). These disorders are caused by mutations of VHL, HIF1/HIF2A, and IDH1/IDH2, respectively (2,12,13). Pulmonary capillary hemangiomas are exceedingly rare in the general population (14).…”

Clinical diagnosis, treatment and screening of the VHL gene in three von Hippel‑Lindau disease pedigrees

“…VHL disease, also known as VHL syndrome, is characterized by a variety of benign, malignant tumors and multiple organ cysts ( 18 ). VHL patients usually develop clinical symptoms after reaching 20 years of age, with 90-100% penetrance of clinical symptoms between 65 and 70 years old ( 19 ).…”

Il versante endocrinologico della sindrome di von Hippel-Lindau (vHLs)

“…Sono infatti note più di 300 mutazioni causanti la vHLs. Le mutazioni che conferiscono il fenotipo I possono essere ampie delezioni e mutazioni non senso mentre il fenotipo II è determinato esclusivamente da mutazioni missenso [3,4].…”

“…In virtù del frequente coinvolgimento surrenalico bilaterale, si dovrebbe considerare, soprattutto nei pazienti pediatrici, la tecnica di adrenal-sparing, che preserva la corticale surrenalica, consentendo di evitare l'ipocorticosurrenalismo permanente [2]. Un importante problema diagnostico di questi soggetti è rappresentato dal fatto che l'analisi istologica non è in grado di definire l'aggressività della lesione e soltanto l'evidenza di metastasi a distanza identifica con certezza le lesioni con prognosi peggiore [3]. In conclusione, tali pazienti necessitano di un'osservazione periodica per tutta la vita, in virtù dell'elevato rischio di recidiva/ricorrenza di malattia anche a lungo termine [2].…”