Skin lesions are often the initial clue seen in neurocutaneous syndromes. As discussed in this chapter, identifying multiple café au lait spots or hypopigmented macules on a skin examination should prompt a more thorough history taking and a directed physical examination.

A definitive diagnosis of neurofibromatosis type 1 (NF1) can be made with a clinical examination that identifies six or more characteristic café au lait macules (CALMs) and axillary freckling. Identifying one of these two findings on a skin examination should raise suspicion for the NF1 and lead to further workup. Similarly the typical hypopigmented macule (ash-leaf spot) and the shagreen patch on the lower back, representing a connective tissue nevus are among the earliest signs of tuberous sclerosis. Neurofibromatosis and tuberous sclerosis are autosomal dominantly inherited neurocutaneous syndromes with variable clinical features a wide spectrum of clinical presentations. Early recognition is essential for proper surveillance and early interventions as necessary.