Background
Hypomelanosis of Ito (HI) is a syndrome with hypopigmented whorls of skin along the Blaschko lines.[1] The old name, incontinentia pigmenti achromians, implies an association with incontinentia pigmenti (IP) and was probably used because hypomelanosis of Ito appears to be the negative image of incontinentia pigmenti. This name was found to be incorrect. Ito first described the syndrome in 1952, with only cutaneous findings. Reports soon followed, with description of multiple other congenital defects, mostly neurologic, skeletal, hair, and dental findings.
Pathophysiology
Chromosomal mosaicism is believed to be the reason that hypomelanosis of Ito is so varied in phenotype. Certain genes, namely, those on 9q33-qter, 15q11-q13, and Xp11, have been implicated in hypomelanosis of Ito; however, no consensus exists about the identity of the hypomelanosis of Ito gene. The human genome project investigators report the hypomelanosis of Ito locus is a balanced translocation of Xp21.2, the location of the COL5A1 gene in a patient with Ehlers-Danlos syndrome. One report of hypomelanosis of Ito involves a pair of monozygotic twins in which only one twin is affected. The Xp11 locus had been previously described in sporadic incontinentia pigmenti, but recent authors believe that this mosaic mutation is truly hypomelanosis of Ito. Trisomy 2 mosaicism has been reported.[2] See the Online Mendelian Inheritance of Man Web site for full details.[3]
Epidemiology
Frequency
International
Hypomelanosis of Ito is rare.
Mortality/Morbidity
Death is rare; hypomelanosis of Ito has only cutaneous involvement. Morbidity depends on severity of the associated abnormality such as seizures.
Race
No clear racial predilection is reported for hypomelanosis of Ito.
Sex
Hypomelanosis of Ito is 1.5-2.5 times more common in women than in men.
Age
Hypomelanosis of Ito is present at birth, and patients usually undergo examination in their first or second years of life. Approximately 75% of patients with hypomelanosis of Ito seek care by the time they are aged 2 years. One fourth of patients seek care after they are aged 2 years, before they are aged 5 years. Skin lesions may become pigmented over time and blend well with normally pigmented skin.
Nehal KS, PeBenito R, Orlow SJ. Analysis of 54 cases of hypopigmentation and hyperpigmentation along the lines of Blaschko. Arch Dermatol. Oct 1996;132(10):1167-70. [Medline].
Gupta S, Shah S, Mcgaw A, Mercado T, Zaslav AL, Tegay D. Trisomy 2 mosaicism in hypomelanosis of Ito. Am J Med Genet A. Oct 15 2007;143A(20):2466-8. [Medline].
McKusic VA. Online Mendelian Inheritance in Man (OMIM) [serial online]. Available at http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim.
Assogba K, Ferlazzo E, Striano P, Calarese T, Villeneuve N, Ivanov I, et al. Heterogeneous seizure manifestations in Hypomelanosis of Ito: report of four new cases and review of the literature. Neurol Sci. Feb 2010;31(1):9-16. [Medline].
Scott A, Micallef C, Hale SL, Watts P. Cortical visual impairment in hypomelanosis of Ito. J Pediatr Ophthalmol Strabismus. Jul-Aug 2008;45(4):240-1. [Medline].
Iype M, Iype T, Geetha S, Retnakumar J. Hypomelanosis of Ito with cerebral malformation. Indian J Pediatr. Nov 2007;74(11):1044-5. [Medline].
Vergine G, Mencarelli F, Diomedi-Camassei F, et al. Glomerulocystic kidney disease in hypomelanosis of Ito. Pediatr Nephrol. Jul 2008;23(7):1183-7. [Medline].
Donnai D, Read AP, McKeown C, Andrews T. Hypomelanosis of Ito: a manifestation of mosaicism or chimerism. J Med Genet. Dec 1988;25(12):809-18. [Medline].
Fritz B, Kuster W, Orstavik KH, Naumova A, Spranger J, Rehder H. Pigmentary mosaicism in hypomelanosis of Ito. Further evidence for functional disomy of Xp. Hum Genet. Oct 1998;103(4):441-9. [Medline].
Glover MT, Brett EM, Atherton DJ. Hypomelanosis of Ito: spectrum of the disease. J Pediatr. Jul 1989;115(1):75-80. [Medline].
Hatchwell E. Hypomelanosis of Ito and X;autosome translocations: a unifying hypothesis. J Med Genet. Mar 1996;33(3):177-83. [Medline].
Pascual-Castroviejo I, Roche C, Martinez-Bermejo A, et al. Hypomelanosis of ITO. A study of 76 infantile cases. Brain Dev. Jan 1998;20(1):36-43. [Medline].
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