In 1882, von Recklinghausen described a group of patients with multiple
tumors arising from the 'endoneurium' of peripheral nerves, and called them '
neurofibromas'. The term
von Recklinghausen disease was used up to the end of the 20th century, when the gene of
neurofibromatosis (NF1) was cloned on chromosome 17q11.2. The gene product is a cytoplasmic
protein termed
neurofibromin, regulating proliferation and maturation of both glial and neuronal progenitors during embryogenesis. Loss of
neurofibromin function determines the hyperactivation of the proto-oncogene RAS, leading to an increased risk of
tumor formation, predominantly affecting the skin, bone and the nervous system. NF1 is clinically and genetically distinct from
neurofibromatosis type 2, characterized by bilateral
vestibular schwannomas and other
nervous system tumors. An increased incidence of
central precocious puberty, diencephalic syndrome, GH deficiency and GH hypersecretion has been described in NF1 children. These conditions are commonly complications of optic pathway
gliomas (OPG) involving the hypothalamic and sellar region. Nevertheless, these endocrine disorders have been observed also in children without evidence of OPG at magnetic resonance imaging. Clinical and laboratory follow-up is crucial in all children with NF1, particularly in those with an OPG, aiming at the early identification of signs suggestive of secondary endocrine alterations.