Hypomelanosis of Ito

David T Hsieh MD (Dr. Hsieh of the Uniformed Services University of the Health Sciences and The University of Texas Health Science Center at San Antonio has no relevant financial relationships to disclose.)
Harvey B Sarnat MD FRCPC MS, editor. (Dr. Sarnat of the University of Calgary has no relevant financial relationships to disclose.)
Originally released June 10, 1997; last updated October 23, 2016; expires October 23, 2019

This article includes discussion of hypomelanosis of Ito, Ito's disease, Ito syndrome, Ito's syndrome, Ito hypomelanosis, Ito's hypomelanosis, pigmentary dysplasia, mosaic dyspigmentation, pigmentary mosaicism, pigmentary mosaicism of the Ito type, hypopigmentation along the lines of Blaschko, nevus depigmentosus, linear and whorled nevoid hypermelanosis, and phylloid hypomelanosis. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

The term “hypomelanosis of Ito” encompasses a heterogeneous group of disorders characterized by hypopigmented skin lesions arranged in whorls, streaks, or both, along the lines of Blaschko (a nonrandom developmental system of cutaneous markings characterizing the distribution of various linear and segmental skin disorders). Even though Ito's original report in 1952 described a purely cutaneous disease, subsequent case reports and case series have recorded a significant association with multiple extracutaneous manifestations, including musculoskeletal and neurologic abnormalities. For hypomelanosis of Ito several models of inheritance have been proposed but not proved, and a number of cytogenetic studies have revealed a wide variety of mosaic chromosomal abnormalities, hence, the heterogeneity of associated systemic features. Thus, it has been suggested that this group of conditions is rather a nonspecific manifestation (ie, a phenotype) reflecting genetic mosaicism. These mosaic phenomena likely disrupt expression or function of pigmentary genes. The author includes updates on the occurrence of hemi-overgrowth in patients with hypomelanosis of Ito.

Key points

 

• Hypomelanosis of Ito is a sporadic neurocutaneous disorder characterized cutaneously by hypopigmented skin lesions arranged in whorls and streaks along the lines of Blaschko.

 

• Though multisystem involvement is common, it is heterogeneous in presentation and commonly manifests with involvement of the neurologic and musculoskeletal systems.

 

• The most common neurologic manifestations include cognitive and behavioral problems in up to 70% and epilepsy in up to 50%.

 

• Neuroimaging findings can include cerebral or cerebellar atrophy, cerebral dysgenesis, or migrational abnormalities.

Historical note and terminology

Lines of Blaschko. Alfred Blaschko (1858 to 1922) was a private practitioner of dermatology in Berlin whose interests ranged from leprosy to occupational skin diseases (Bologna et al 1994).

Image: Alfred Blaschko
In 1901 he presented his original description on the distribution patterns of linear skin disorders after having examined more than 140 patients with linear lesions such as epidermal nevi, sebaceous nevi, and nevus lipomatosus, and after carefully transposing the pattern in each patient onto dolls and statues (Blaschko 1901; Jackson 1976; Bologna et al 1994).
Image: Lines of Blaschko
A composite diagram of these distribution patterns was then drawn that has subsequently been referred to as the lines of Blaschko. In 1976, Jackson introduced the concept of the lines of Blaschko into the English-language literature, although it had been well known in the European community for decades (Bologna et al 1994). Happle added to Blaschko's original diagram lines (confined to the trunk and limbs) localized to the posterior scalp (Happle 1985; Bologna et al 1994; Happle 2006).

Hypomelanosis of Ito. In 1952 Minor Ito described a 22-year-old Japanese girl whose skin of the upper half of her body looked as “if the normal pigment was brushed off.” The depigmented skin lesions were widespread and symmetric, arranged in irregular shapes with “zigzag borders and splash-like spots” on the trunk and in a “linear pattern” down her arms. He defined these lesions as “nevus depigmentosus systematicus bilateralis” (Ito 1952). No other physical abnormality was reported apart from asymmetry of breast size. At that time, Ito coined the term incontinentia pigmenti achromians (Pascual-Castroviejo and Ruggieri 2007) because the pattern of color loss was similar to that of the hyperpigmented changes seen in incontinentia pigmenti of the Bloch-Sulzberger type (OMIM #308300). Subsequent observations expanded the phenotype and the name hypomelanosis of Ito was proposed to avoid confusion with incontinentia pigmenti (Jelinek et al 1973). However, this term was criticized because Ito's original patient was described as having “depigmented,” not hypopigmented lesions (Ito 1952; Sybert 1990; Sybert 1994; Ruggieri and Pavone 2000). Possibly, the original patient by Ito may have had incontinentia pigmenti, as the author himself believed (Ito 1952). Further terms have been used such as Ito disease, Ito syndrome, and Ito hypomelanosis.

Proposed changes in terminology included the terms pigmentary dysplasia, mosaic dyspigmentation, pigmentary mosaicism, pigmentary mosaicism of the Ito type, or hypopigmentation along the lines of Blaschko to reflect the disease pathogenesis or recall the cutaneous patterns (Donnai 1996; Sybert 1990; Editorial 1992; Moss et al 1993; Sybert 1994; Ruggieri and Pavone 2000; Pascual-Castroviejo and Ruggieri 2007). Despite these criticisms the term hypomelanosis of Ito is still used.

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