Topical Review: Hypomelanosis of Ito: Clinical Syndrome or Just Phenotype?

Abstract

The term hypomelanosis of Ito is applied to individuals with skin hypopigmentation along the lines of Blaschko. Even though originally described as a purely cutaneous disease, subsequent reports have included a 33% to 94% association with multiple extracutaneous manifestations mostly of the central nervous and musculoskeletal systems leading to frequent characterization as a neurocutaneous disorder. A number of reports claimed familial occurrence and supported single gene inheritance for hypomelanosis of Ito, but none has been proved. Miscellaneous chromosomal mosaicisms have been demonstrated in some but not all affected individuals. Thus, it has been suggested that hypomelanosis of Ito is not a single condition but rather a nonspecific manifestation (ie, a phenotype) of chromosomal mosaicism and that this term should now be dropped. In this article, we review these developments focusing on the neurologic and genetic aspects of hypomelanosis of Ito. Our personal experience with 41 hypomelanosis of Ito patients and literature review led us to conclude that (1) the term hypomelanosis of Ito has been often misapplied to individuals with nonspecific "patchy depigmentation of the skin" who had several conditions of different etiologies; (2) the white matter involvement seen at neuroimaging in most of our hypomelanosis of Ito patients was similar to that reported in well-defined neurocutaneous disorders, including Sjögren-Larsson syndrome and incontinentia pigmenti; (3) whatever figures we take for associated central nervous system abnormalities in hypomelanosis of Ito, these represent the most frequent extracutaneous findings and, therefore, the use of the term neurocutaneous disorder for hypomelanosis of Ito might well be appropriate.

Pigmentary mosaicism following the lines of Blaschko in a girl with a double aneuploidy mosaicism: (47,XX,+7/45,X)

“…Disorders with pigmentary anomalies along the lines of Blaschko can be associated with abnormal systemic features, particularly of the central nervous, musculoskeletal, and ocular systems [Nehal et al, 1996;Ruggieri and Pavone, 2000]. Nehal et al [1996] analyzed the symptoms and signs of 54 patients with hypopigmentation and hyperpigmentation along the lines of Blaschko.…”

Hypomelanosis of Ito

“…HOI is the third most common neurocutaneous disorder, after neurofibromatosis and tuberous sclerosis [4,5]. It is diagnosed in 1 per 8000-10000 unselected patients in general paediatric outpatient clinic and 1 out of every 790 in a paediatric dermatology clinic [6,7].…”

“…Chromosomal abnormalities, particularly translocation and mosaicism have been reported in approximately 50% of cases [5]. It is suggested that HOI is not a single condition but a phenotype of chromosomal mosaicism [4].…”

“…Multiple extracutaneous abnormalities involving the central nervous system, eyes and musculoskeletal structures occur in 76-94% of patients [3,4,9]. Convulsions and mental deficiency are common.…”

Hypomelanosis of Ito presenting with adult-onset dementia and marked enlarged Virchow-Robin spaces

“…HI or incontinentia pigmenti achromians (MIM#300337) represents a heterogeneous group of early-onset sporadic neurocutaneous disorders, resulting from chromosomal mosaicism 1 . Neurological manifestation may include: cognitive impairment, epilepsy, spasticity, cerebellar ataxia and microcephaly 2 .…”