Hypomelanosis of Ito 

Updated: May 07, 2018
Author: Manuel Valdebran, MD; Chief Editor: Dirk M Elston, MD 

Overview

Background

Hypomelanosis of Ito is a pigmentary mosaicism characterized by a clone of skin cells with decreased ability to produce pigment. The clinical pattern is characterized by hypopigmented streaks and whorls running along the lines of Blaschko, characteristically involving more than two body segments. Around one fifth of patients have a patchy presentation without a specific distribution pattern.[1] Various terms have been used to describe this mosaicism, including Blaschkoid dyspigmentation, pigmentary mosaicism of the hypopigmented type, and incontinentia pigmenti achromians.[2]

Ruiz-Maldonado et al established criteria for hypomelanosis of Ito that include nervous system or musculoskeletal anomalies[1] ; however, the strength of these associations has been questioned in other studies.[2] Currently, hypomelanosis of Ito is considered an umbrella term. Some cases may present with isolated cutaneous findings, while a portion have associated systemic anomalies, most commonly of the nervous system.[3] Larger studies are required to provide further evidence to support possible associations with different anomalies.

See the image below.

Hypomelanosis of Ito on the torso. Hypomelanosis of Ito on the torso.

 

Pathophysiology

The affected areas seen in hypomelanosis of Ito result from postzygotic mutations in a variety of pigmentation-associated genes, resulting in a clone of skin cells with reduced capacity to produce pigment. Structural or numerical chromosomal aberrations present in these clones of cells have been linked with this entity. Around 90% of these chromosomal aberrations are present in the locations of genes involved in pigmentation.[4] Associations of different numerical chromosomal disorders can be found in the literature, such as trisomy of chromosome 2, 13,14, 18, or 20 mosaicisms.[5, 6]

Extracutaneous manifestations might be due to the presence of different genetic defects.

Etiology

Chromosomal mosaicism and sporadic mutations are the causes of hypomelanosis of Ito.

Epidemiology

Frequency

Epidemiological studies in Catania, Italy have estimated a prevalence of 1 case per 7,540 births and 1 in 82,000 within the total population.[7]

Race

No clear racial predilection has been reported for hypomelanosis of Ito.

Sex

Hypomelanosis of Ito is 0.7-2.5 times more common in women than in men.[8]

Age

Hypomelanosis of Ito is present at birth, and patients usually undergo examination in their first or second year 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 between ages 2 and 5 years. Skin lesions may become more pigmented over time and blend well with normally pigmented skin.

Prognosis

The prognosis is determined by any associated abnormalities. The prognosis is excellent for the cutaneous findings. Death is rare. Morbidity depends on severity of the associated abnormalities, such as seizures.

Patient Education

Genetic counseling may be recommended. However, the risk of hypomelanosis of Ito transmission is considered low, except when X-linked mutations are present in female patients.

 

Presentation

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 that are usually seen in incontinentia pigmenti.

A family history of hypomelanosis of Ito is rare.

The patient or parents should be asked about the following:

  • Seizures

  • Mental retardation

  • Developmental delay

  • Deafness

  • Visual problems

  • Headache

  • Tooth or mouth problems

The most common reported associations are congenital abnormalities, mental retardation, and seizures.[9] Cerebral malformations may occur, and visual impairment may be cortical in nature.[10, 11] Glomerulocystic kidney disease has also been reported.[12]

Physical Examination

Small 0.5- to 1-cm hypopigmented macules coalesce to form reticulated patches along the lines of Blaschko, usually stopping at the midline. They are most often seen on the trunk and limbs. The macules/patches cover more than two dermatomes and are often on both sides of the body. A Wood lamp enhances the pattern, especially in white patients.[8] See the images below.

Hypomelanosis of Ito on the arm. Hypomelanosis of Ito on the arm.
Hypomelanosis of Ito highlighted with a Wood lamp. Hypomelanosis of Ito highlighted with a Wood lamp.
Hypomelanosis of Ito on the torso. Hypomelanosis of Ito on the torso.

Careful full body examination is needed to detect dysmorphism, including 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.

Complications

Complications may occur as a result of associated abnormalities.

 

DDx

Differential Diagnoses

  • Fourth stage of incontinentia pigmenti

  • Linear and whorled nevoid hypermelanosis

  • Linear leukoderma

  • Nevus depigmentus

 

Workup

Laboratory Studies

Only history taking and physical examination with special attention to the neurologic and ophthalmologic findings are necessary to detect abnormalities associated with hypomelanosis of Ito.

If genetic and/or chromosomal testing are considered, these should be coordinated with someone who is conducting research on this disease.

Imaging Studies

Perform imaging only as indicated by the features of the history and physical examination.

CT and/or MRI of the brain should only be performed in those with neurologic symptoms.

Skeletal radiography should be performed in hypomelanosis of Ito patients with apparent bony abnormalities.

Other Tests

Perform EEG in hypomelanosis of Ito patients with seizure disorders.

Perform electromyelography (EMG) in those with hypotonia.

Histologic Findings

Histological findings include a decreased amount of melanin present in keratinocytes and melanocytes along the basal layer of the epidermis. Special stains such as Fontana-Masson and/or immunostains such as SOX 10, MITF, or Melan A may be used to evaluate these changes. Ultrastructurally, there is a reduction in melanosomes, both in melanocytes and keratinocytes.[13, 14]

 

Treatment

Medical Care

No treatment is administered for the cutaneous findings of hypomelanosis of Ito. Cover-up makeup can be used for cosmesis if desired.

Associated diseases, including the following, require appropriate specialty care:

  • Seizures

  • Mental retardation

  • Hearing abnormalities

  • Tooth deformities

  • Visual problems

  • Orthopedic problems

Diagnosis is important to guide genetic counseling.

Surgical Care

No surgical treatment is required for the cutaneous problems. Consult a surgeon as needed for possible associated abnormalities.

Consultations

Consult a genetic counselor. Consult a neurologist, psychiatrist, orthopedic specialist, dentist, or ophthalmologist, as indicated per medical history and physical examination findings.

Activity

No limitations on activity are required.

Prevention

Genetics counseling may aid in the prevention of hypomelanosis of Ito.

Long-Term Monitoring

Routine outpatient care is sufficient, except when associated abnormalities require additional care.