Incontinentia pigmenti (IP) is a rare X-linked dominant neurocutaneous disorder 
affecting ectodermal tissue: skin, eyes, central nervous system, hair, nails, 
and teeth. It is usually lethal for males in utero. The involved gene is NEMO, 
an essential component of the nuclear factor-kappa B (NF-κB) signaling pathway. 
Skin lesions are highly diagnostic, occurring in neonates, with a particular 
distribution on Blaschko lines. The severity of the disease is related to ocular 
and neurological impairment. The hallmark of ocular IP is retinal vasculopathy 
including peripheral retinal vascular nonperfusion, macular infarction and 
neovascularization, and preretinal neovascularization. CNS involvement consists 
of seizures, mental retardation, hemiparesis, spasticity, microcephaly, 
cerebellar ataxia, and coma. It often occurs in neonates. Some patients have 
persistent pharmacoresistant seizures throughout life. MRI findings consist 
essentially in: white-matter lesions; scattered cortical neuronal necrosis; 
multiple cerebral infarctions; cerebral atrophy, hypoplasia of the corpus 
callosum, encephalomalacia and neuronal heterotopia. A predominant role of 
vascular occlusive phenomena in small vessels is highly suspected. In fact 
several intricate mechanisms could be discussed: vascular, inflammatory, 
developmental mechanisms. Their role and predictive factors of IP CNS 
involvement in neonatal IP need to be better understood to identify effective 
innovative therapies. Hypomelanosis of Ito can occur in the neonate, infancy, or 
childhood, be isolated or diffuse, often following the Blaschko lines, and can 
fade in childhood or adulthood. It is due to reduced melanin in the epidermis. 
Eye, central nervous (mental retardation, epilepsy, language disabilities, motor 
system dysfunction, psychiatric symptoms including autism - with frequent 
cortical malformations including hemimegalencephaly and white matter 
involvement), and musculoskeletal systems can also be affected. Mosaicism with 
various chromosomal rearrangements has been reported.