Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus (EN) syndrome, featured by co-occurrence of speckled lentiginous nevus (SLN) and nevus sebaceous (NS). The underlying mechanism has not been clarified. Pathogenic mutations in HRAS, KRAS and BRAF gene are recently recognized as the genetic cause of PPK. Here we present a case of Chinese PPK with a mosaic mutation in HRAS gene. Physical examination of the 4-year-old male proband showed NS locating on the scalp, with EN and SLN on trunk and extremities. Except congenital fundus vascular tortuosity, no evidence of extracutaneous abnormalities was found in this case. A rare heterozygous missense c. 181 C>A mosaic mutation in HRAS was identified in samples from NS, EN and pigmented nevus using next-generation sequencing and Sanger sequencing. Meanwhile, no mutation was found in the non-lesion skin, hair follicle, or blood DNA. Recent breakthrough in clinical manifestation, genetic mutation and prognosis of PPK is also reviewed.

The co-existence of papular nevus spilus (PNS) and ipsilateral extracutaneous abnormalities involving peripheral nerves of the skin or muscles was originally described as \"speckled lentiginous nevus syndrome\". To avoid confusion with macular nevus spilus, the condition was recently re-named \"papular nevus spilus syndrome\". In addition to 14 published cases, we identified six new cases via a search of the worldwide literature. New diagnostic criteria are suggested: (1) presence of a PNS; (2) presence of a neurological or skeletal abnormality which is usually ipsilateral to the nevus; and (3) absence of a nevus sebaceus. According to current knowledge, PNS syndrome is a rather rarely occurring, sporadic disorder that can be considered to be part of a spectrum of mosaic RASopathies, which includes isolated PNS, isolated nevus sebaceus, PNS syndrome, Schimmelpenning syndrome, and phacomatosis pigmentokeratotica.

Speckled lentiginous nevus syndrome has been described in individuals with a speckled lentiginous nevus with rare associated neurologic deficits. Because speckled lentiginous nevus syndrome almost always affects adults, it is not typically considered when evaluating children. We present the first reported case of speckled lentiginous nevus syndrome presenting in a young child with muscle atrophy and motor deficits affecting muscles along the same distribution as the speckled lentiginous nevus.