NORD gratefully acknowledges Raymond E. Boissy, PhD, Professor of Dermatology & Cell Biology, Department of Dermatology, University of Cincinnati College of Medicine, for assistance in the preparation of this report.
Hypomelanosis of Ito is a rare condition characterized by distinctive skin changes, in which areas of the body lack skin color (hypopigmentation). These skin changes may present as patches, streaks or spiral-shaped (whorled) areas. In many cases, additional symptoms affecting areas outside of the skin also occur. There are a wide variety of symptoms potentially associated with hypomelanosis of Ito. Neurological findings such as seizures and developmental delays and musculoskeletal symptoms such as abnormal curvature of the spine (scoliosis) are commonly associated with this condition. Because of the neurological and skin symptoms hypomelanosis of Ito may be referred to as a "neurocutaneous" syndrome. However, in many cases the condition arises from genetic irregularities that are present in some cells of the body, but not in others (mosaicism). Some researchers believe that hypomelanosis of Ito does not represent a distinct disorder but rather a symptom common to a group of disorders involving genetic mosaicism.
The most distinctive finding associated with hypomelanosis of Ito is characteristic skin changes. Most affected individuals develop areas that lack skin color (hypopigmentation). Any area of the body may be involved although the scalp, palms and soles are rarely affected. Skin changes may occur as patches, streaks or spiral-shaped (whorled) areas of discoloration and may affect one side of the body (unilateral) or both sides (bilateral). Affected areas of skin are usually normal otherwise. The skin lesions usually appear during the first year of life and remain unchanged through childhood, but may fade or darken in adulthood.
In some cases of hypomelanosis of Ito, additional non-cutaneous features may occur. It is important to note that the specific symptoms that occur vary greatly from case to case and affected children will not have all the symptoms discussed below. Because children with the characteristic skin changes of hypomelanosis of Ito and no associated abnormalities may go unreported, determining the actually frequency of associated findings is difficult. The number of affected individuals with additional symptoms has been estimated to be anywhere from 30-90 percent.
Neurological findings may occur in some cases including seizures that occur during infancy and are often resistant to therapy, some degree of cognitive impairment, and delays in attaining milestones that require the coordination of muscular and mental activity (psychomotor retardation). In some cases, one side of the brain may be larger than the other (hemimegalencephaly).
Less often, some individuals have crossed eyes (strabismus), eyes that a spaced apart wider than normal (hypertelorism), cleft palate, cleft lip, and dental anomalies such as missing teeth (anodontia). Loss of hair usually in a patchy pattern (alopecia) may also occur. Some infants may have microcephaly, a condition that indicates that the head circumference is smaller than would be expected for age and sex; others may have macrocephaly, which indicates that head circumference is larger than would normally be expected.
A variety of skeletal abnormalities have occurred in individuals with hypomelanosis of Ito including abnormal side-to-side curvature of the spine (scoliosis), disproportionate length of the legs (limb length discrepancy), and abnormal fixation or “locking” of the pinky in a bent position (clinodactyly). Diminished muscle tone (hypotonia) may also occur.
Additional symptoms that may affect individuals with hypomelanosis of Ito include additional eye abnormalities, overgrowth of one side of the body (hemihypertrophy), heart (cardiac) abnormalities, kidney (renal) malformations, and abnormalities of the genitourinary tract, which contains the reproductive organs and urinary system.
The exact cause of hypomelanosis of Ito is unknown. Many cases are associated with genetic mosaicism and sporadic gene mutations. Genetic mosaicism is the term for individuals who have two distinct cell lines in the body. The two cell lines have differences involving the chromosomes (chromosomal mosaicism).
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
In many individuals with hypomelanosis of Ito, certain cells have the normal 46 chromosomes (one cell line) while others cells do not have the normal 46 chromosomes (second cell line). This second cell line may contain various abnormalities affecting the chromosomes such as a mutation in a specific gene, or the presence of an extra material on a chromosome (trisomy), loss of a portion of chromosome (monosomy), or a chromosomal translocation. Translocations occur when portions of certain chromosomes break off and are rearranged, resulting in shifting of genetic material and an altered set of chromosomes. Specific chromosomal abnormalities have been identified in certain cases of hypomelanosis of Ito including ones affecting chromosome 9q33, chromosome 15q11-q13, chromosome Xp11 and Xp21.2. Chromosomal abnormalities have been identified in approximately 60 percent of cases of hypomelanosis of Ito.
The chromosomal abnormalities affecting hypomelanosis of Ito occur after fertilization, often for unknown reasons (spontaneously). The disorder is not inherited. The specific gene(s) involved in the development of hypomelanosis of Ito have not been identified.
In earlier reports, hypomelanosis of Ito affected women more often than men by a ratio of 2.5:1. More recent, larger studies suggest that the difference may not be as large. The incidence of hypomelanosis of Ito is estimated to be 1 in 8,000-10,000 people in the general population. The symptoms usually become apparent during the first or second year of life. Hypomelanosis of Ito was first described in the medical literature in 1952.
A diagnosis of hypomelanosis of Ito is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings and a variety of specialized tests such as the finding of chromosomal mosaicism in keratinocytes (the major cell of the outer layer of the skin [epidermis]) obtained from an area of affected (hypopigmented) skin. Computed tomography (CT) scans or magnetic resonance imaging (MRI) may be able to detect structural abnormalities of the brain if neurological abnormalities are present.
During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs, tissues and structures.
The treatment of hypomelanosis of Ito is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, dermatologists, neurologists, specialists who diagnose and treat skeletal disorders (orthopedists), dental specialists, specialists who diagnose and treat eye disorders (ophthalmologists), surgeons and other healthcare providers may need to systematically and comprehensively plan an affect child's treatment.
The characteristic skin abnormality (hypopigmentation) of hypomelanosis of Ito tends to darken or fade without treatment. Some individuals may use cosmetics to hide or darken these areas. Antiseizure medications (anticonvulsants) may be used to treat infants and children with seizures, but are ineffective in some cases. Surgical techniques to treat seizures may be necessary for some affected individuals.
Additional treatment is symptomatic and supportive and consultation with proper specialists may be necessary. For example, consultation with an orthopedist may be necessary to treat scoliosis.
Services that may be beneficial to some children with hypomelanosis of Ito include special remedial education and other medical, social, and/or vocational services. Genetic counseling may be of benefit for affected individuals and their families.
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