eMedicine Specialties > Dermatology > Diseases of Pigmentation

Hypomelanosis of Ito

Author: John Ratz, MD, MBA, Staff Dermatologist, Mohs Surgeon, Center for Dermatology and Skin Surgery, Inc
Coauthor(s): Ned Gross, MD, President, Piedmont Dermatology Center, PC
Contributor Information and Disclosures

Updated: Aug 31, 2009

Introduction

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

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.

Clinical

History

• Patients with hypomelanosis of Ito usually seek care from a dermatologist, pediatrician, or neurologist by the time they are aged 2 years.
• The hypopigmentation is not preceded by vesicular or verrucous lesions. This feature is in contrast to the usual presentation of incontinentia pigmenti.
• A family history of hypomelanosis of Ito is rare.
• The patient or parent should be asked about the following:
  • Seizures
  • Mental retardation
  • Developmental delay
  • Deafness
  • Visual problems
  • Headache
  • Tooth or mouth problems
• Congenital abnormalities, mental retardation, and seizures are the most commonly associated conditions, as reported in the medical literature. Cerebral malformations may occur and visual impairment may be cortical in nature.^4,5 Glomerulocystic kidney disease has been reported.⁶
• The literature contains reviews, mostly from neurology departments, that report rates of hypomelanosis of Ito-associated neurologic abnormalities as high as 75-94%.
  • The present authors believe that these reviews are inherently biased.
  • More recent groups estimate that the associated anomaly rate is 30-50%.

Physical

• Small 0.5-1-cm hypopigmented or white macules coalesce to form reticulated patches along the lines of Blaschko.
  • The macules cover more than 2 dermatomes and are often on both sides of the body.
  • The patches are not symmetric.
  • A Wood lamp enhances the pattern, especially in white patients (see Media Files 1-3).

• Careful full body examination is needed to detect dysmorphism, such as the following:
  • Cleft palate
  • Hemihypertrophy
  • Limb, hand, and/or foot abnormalities
  • Nail abnormalities
  • Hypotonia
  • Teeth abnormalities
  • Hair anomalies
  • Face and/or skull anomalies
• Neurologic examination is essential to evaluate neural tumors, seizures, and psychomotor delay.
• The common finding in all these patients is the pigmentary changes and the associations with neurologic, skeletal, and other congenital abnormalities.
• Normal systemic findings are present in approximately 50% of patients with hypomelanosis of Ito.

Causes

Chromosomal mosaicism and sporadic mutations are the causes of hypomelanosis of Ito, but the identity of a specific gene has not been confirmed.

• Probably, several gene abnormalities cause the phenotype that is recognized as hypomelanosis of Ito.
• For this reason, some authors believe that hypomelanosis of Ito is a symptom and that it may not be a distinct disease.
• Some believe that hypomelanosis of Ito results in the somatic mosaicism of the incontinentia pigmenti gene, which makes the condition less lethal.
• The common findings in all these patients are the pigmentary changes and the associations with neurologic, skeletal, and other congenital abnormalities.
• However, the authors believe that incontinentia pigmenti and hypomelanosis of Ito are distinct diseases with separate gene loci: Xp28 for incontinentia pigmenti and 9q33-ter, 15q11, Xp11, and Xp21.2 for hypomelanosis of Ito.
• The previously described sporadic incontinentia pigmenti gene at Xp11 is now believed to be related to hypomelanosis of Ito.

• Search for CME/CE on This Topic »

• Hypomelanosis of Ito (Pediatrics: General Medicine)
• Incontinentia Pigmenti (Neurology)