Hypomelanosis of Ito (Incontinentia Pigmenti Achromians)

Medical Definition

Figure X-1 | Photo courtesy of BMJ Journals Opens in new window

Hypomelanos of Ito (HI), (also called incontinentia pigmenti achromians—OMIM 300337) is a neurocutaneous disorder which manifests at birth or in infancy with sharply demarcated, hypopigmented macular lesions, with a distinctive linear or whorled pattern that can occur on any part of the body, particularly around the extremities and trunk. It is associated with neurologic deficits, epilepsy and asymmetrical abnormalities in other organs.

The pattern observed in hypomelanosis of Ito resembles a negative image of the pigmentation seen in incontinentia pigmenti. Researchers believe the condition occurs as a result of various genetic anomalies within the same individual.

Mosaicism Opens in new window, chimerism Opens in new window, post-zygotic mutations, or X chromosome inactivations Opens in new window have all been implicated. The lesions often follow the lines of Blaschko Opens in new window, which are whorled or swirl-like patterns that form around the extremities and trunk (Figure X-1).

Historical Background

Hypomelanosis of Ito (HI) was brought into prominence in 1952 by the Japanese dermatologist Minor Ito, when he described a 21-year-old woman who had a widespread, symmetric pattern of depigmented whorls and streaks that had its onset at the age of 5 years.

Ito interpreted the anomaly as a case of nevus depigmentosus systematicus bilateralis Opens in new window and called it incontinentia pigmenti achromians, because the distribution of the depigmented lesions was similar to that of the hyperpigmented streaks of incontinentia pigmenti of the Bloch-Sulzberger type.

Because the pigmentary lesions are more easily recognizable in darker skin the first cases that were published were of patients of Japanese, African American, and Hispanic origin. Paradoxically, in Europe, HI developed to a more generally recognized “entity” at a time when it became evident, on the basis of cytogenetic studies, that this entity did not exist.

The importance of HI derives from its frequent association with epilepsy Opens in new window and mental retardation Opens in new window. Mosaics for chromosomal abnormalities have been reported for several years in HI patients but are not present in every case.

Some authors have argued that HI is merely a symptom or a descriptive term that occurs in many conditions, all of which are characterized by chromosomal mosaicism.

In support of this argument, skin lesions which conform to Baschko lines represent genetic mosaicism, but are not always an indication of HI.

On the contrary, some authors think that HI is a symptom of mosaicism. Given the high frequency of neurological dysfunction associated with HI, the absence of typical neonatal signs of incontinentia pigmenti (IP) in all cases of HI, and the absence of chromosomal anomalies in many patients with HI, this hypothesis is difficult to prove.

Clinical Manifestations

Hypomelanosis of Ito is a multisystem disorder with possible anomalies in any of the organs, but the skin and the central nervous system (CNS) are the areas most affected.

1. Skin

The abnormal skin consists of hypopigmented zones or spots with irregular borders, whorls, patches or linear white streak lines of the Blaschko type. These lines are associated with mosaicism.

Pigmentary patterns associated with human mosaicism may show several types: lines of Blaschko narrow band type or broad band type, checkerboard pattern, phylloid pattern, and a patchy pattern without mid-line separation.

All these cutaneous changes are associated with mosaicism, but not all have hypopigmented zones and not all correspond to HI. These changes are observed within the first year of age in about 64% to 70% of patients.

The hypopigmented zones can occur in any part of the mentioned zones and in any part of the body: head, face, neck, trunk or extremities. They also have been observed in the iris. It is a necessary prerequisite that hypopigmented skin not be preceded by vesicular or verrucous stages because cutaneous lesions in the IV stage of incontinentia pigmenti (IP) Opens in new window are indistinguishable from those of HI.

Zones of hypomelanosis are more easily detected in dark-skinned individuals. Inspection with a Woods lamp Opens in new window, however, may be necessary to distinguish hypochromic zones Opens in new window, especially in fair-skinned people.

The extent of the hypopigmented cutaneous lesion does not correlate either with severity of neurological disease or with neuroradiological or histological findings. It appears related, however, to the early onset of symptoms.

Segmental nevus depigmentosus Opens in new window and cutaneous hypopigmented zones of HI are indistinguishable in appearance. However, segmental nevi Opens in new window, even when distributed along Baschko lines, are typically benign lesions rarely associated with systemic features, while HI is often associated with neurological disorders.

Other types of cutaneous lesions associated with HI include café-au-lait spots Opens in new window, nevus marmorata, angiomatous nevi, nevus fusceruleous of Ota, and Mongolian blue spot.

Alterations in hair color, diffuse alopecia, tricorrhexia, and white-grayish hair color are common. Some patients have alopecia of some zones of the scalp until 3–5 years of age, when trichorrhexia and gray-white hair appear.

Macrocephaly occurs in 16% of the patients with HI and is usually associated with coarse facial features. Sweat glands and fingernails also may be abnormal. Limb malformations, especially affecting the fingers, occasionally occur.

2. Oral

Oral anomalies consist of defective dental implantation, partial anodontia, dental hypoplasia or dysplasia, conical teeth, and defective enamel.

Hamartomatous cuspids protruding from the dental crowns of permanent teeth might be histologically reminiscent of odontoma. Bifid uvula and submucosal cleft palate are rarer anomalies.

3. Nervous System

The most frequent complications of HI are related to CNS involvement. The incidence of neurological disease is reported to be as high as 94% or 80%, with some estimates as low as 61%.

The most frequent neurological disorder is mental retardation. An intellectual quotient (IQ) below 70, that is to say below borderline, is reported in 57% to 70% of patients. Only 22% of the patients have normal intelligence (IQ more than 85).

Between 8% and 10% of the patients with mental retardation exhibit autistic behavior. And most these patients with autistic behavior previously have had infantile spasms or other severe seizure types. The association of mental retardation with seizures is seen in 65% of cases.

The second most frequent neurological complications of HI is epileptic seizures, which occur in 37% to 53% of the patients with HI.

Seizures Opens in new window commonly appear in the first year of life and usually are often refractory to anticonvulsant drugs. They are mostly associated with mental retardation.

Both seizures and mental retardation Opens in new window may be caused by abnormal cerebral migrational anomalies and may be accompanied by macrocephaly Opens in new window or microcephaly Opens in new window.

4. Tumors

Various benign tumors have been reported with HI, including cystic teratoma, diploic epidermoid cyst, mature sacrococcygeal dysembryonal tumor, choroid plexus papilloma, and dental hamartomatous tumors.

Malignant tumors such as medulloblastoma are rare. Malignant transformation of a hypomelanotic zone of the skin is occasionally reported. Benign tumors are associated with chromosomal abnormalities.

Therapeutics

Presently there is no specific treatment for HI. Camouflage may be employed for cosmetic concerns. Seizures should be treated with anticonvulsant drugs in doses appropriate for the age and weight of the patient.

Phenytoin, carbamazepine, valpronic acid, vigabatrin, lamotrigene, gabapentin, topiramate, and benzodiazepines are the most useful.

Corticosteroids, adrenocorticotropic hormone (ACTH), and vigabatrin have been used for the treatment of infantile spasms. Motor disturbances may be minimized with good physiotherapy and orthopedic care.

Mental retardation is approached educationally rather than medically, and training must be appropriate to the patient’s individual capabilities.

Ocular, oral, urogenital, and other disturbances must receive appropriate individual treatment. No special treatment is indicated for the cutaneous lesions.