Which neurocutaneous syndrome is characterized by cafe-au-lait spots and multiple neurofibromas?

• A. NF1
• B. NF2
• C. Tuberous sclerosis
• D. VHL disease

Answer: (B)

Cafe-au-lait spots together with multiple neurofibromas point to Neurofibromatosis type 1. This condition arises from a pathogenic variant in the NF1 gene on chromosome 17, leading to loss of function of neurofibromin, a tumor suppressor. Clinically, you expect multiple café-au-lait macules, axillary or inguinal freckling, and cutaneous neurofibromas; other features can include Lisch nodules in the iris and optic pathway gliomas. NF1 is inherited in an autosomal dominant manner with variable expression. This is distinct from NF2, which centers on bilateral vestibular schwannomas; tuberous sclerosis, which features ash-leaf spots and facial angiofibromas; and VHL disease, known for hemangioblastomas and pheochromocytoma/RCC.