Pediatric Hypomelanosis of Ito Clinical Presentation

  • Author: Camila K Janniger, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: May 16, 2011
 

History

Hypomelanosis of Ito (HI) syndrome may involve many organs. Several manifestations, such as seizures and mental retardation, can be elicited in the history. For the sake of better understanding the subject, data from the history and physical examination are fused into a discussion of the signs and symptoms of each organ system’s involvement. The dermatological alterations are discussed first, followed by the description of systemic involvement.

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Physical

Skin and neurological examinations are crucial for diagnosis; a thorough examination is extremely important.

Dermatological manifestations

Hypochromic lesions in distinctive patterns (eg, whirls, patches, streaks) characterize this syndrome; they often resemble whirled marble. The lesions may be unilateral (46%) or bilateral, and usually show a midline cutoff.

Patients with hypomelanosis of Ito and hemimegalencephaly often have unilateral skin lesions. They are contralateral to the side of brain malformation and may show a zigzag pattern of lines. The hypochromic lesions are readily visualized in patients with pigmented skin, such as blacks, Asians, Spaniards, and Hispanic persons (eg, Mexicans). In children with fair skin, the use of a Wood lamp (ultraviolet light) is helpful in demonstrating these hypochromic lesions, which develop on the trunk, legs, arms, and face. They are more prominent in the ventral surface of the trunk and flexor surface of the limbs. The lesions are located on both the torso and the extremities in 59% of patients, on just the torso in 23% of patients, and exclusively on the extremities in 6% of patients. Some advocate stricter criteria for diagnosis, requiring cutaneous involvement of 2 or more segments for a diagnosis of hypomelanosis of Ito.

Skin lesions usually appear during the first year of life (70%) and may be noticeable at birth (54%). Lesions are not visible until mid childhood in rare cases.

Hypopigmented or depigmented lesions may appear in swirls or patches with irregular borders. They tend to run parallel to one another, following the lines of Blaschko; however, hypomelanosis of Ito is not the only syndrome associated with pigmentary anomalies along the lines of Blaschko. In 22% of the patients, lesions are patchy (square or rounded) rather than linear.

In linear or whorled nevoid hypermelanosis and nevus depigmentosus, lesions also follow these lines. The lines of Blaschko are relatively consistent and distinct from dermatomal lines. They represent orderly migration of mesodermal and ectodermal precursors during embryogenesis, occurring after X inactivation or activation. Genetic alterations (see Pathophysiology) or other problems that perturb morula cells and their daughter cells generate the swirl pattern of hypopigmentation along the lines of Blaschko. The color changes observed in skin lesions of hypomelanosis of Ito may be present at birth but are frequently more obvious later in infancy or early childhood.

Hypohidrosis of hypopigmented skin can be detected in hypomelanosis of Ito by application of iodine and starch in the skin, followed by a subcutaneous injection of pilocarpine hydrochloride.

Nonspecific skin lesions are reported in 20-40% of individuals with hypomelanosis of Ito. These lesions are most frequently café-au-lait spots, but the following lesions have also been described:

  • Persistent mongolian blue spots
  • Nevus of Ota
  • Nevus marmoratus and angiomatous nevi
  • Soft fibroma
  • Pilomatrixoma
  • Aplasia cutis
  • Atopic dermatitis

Hair abnormalities include the following:

  • Slow growth
  • Diffuse alopecia
  • Trichorrhexis
  • Widow’s peak
  • Generalized hirsutism
  • Facial hypertrichosis
  • Coarse and curly hair
  • Low hairline (7% of patients)
  • Appearance of a zone of alopecia or white hair in the scalp (may precede hypopigmented lesions)

Fingernails may show some alterations, especially ungual hypoplasia.

Abnormal sweat glands are reported.

Hypomelanosis of Ito may rarely been seen in association with the Sturge-Weber syndrome.[7]

Neurological manifestations

Neurological involvement is found in 76% of patients during the first decade of life. Mental retardation and seizures are the most common presenting symptoms.

In one series of 19 patients, 10 displayed neurological symptoms before cutaneous symptoms arose; however, the proportion of patients with neurological involvement is clearly biased.[8] The pattern of referral is as high as 84% in a pediatric neurology clinic–generated series but somewhat lower in a dermatologist-generated series. When systemic involvement was used as a key diagnostic criterion, as many as 90% of the patients were found to have neurological involvement. Approximately 50% of the patients presented with seizures, although a lower frequency (37%) was reported in the pediatric dermatology clinic–based series. Generalized tonic-clonic seizures were most common (25%), whereas partial seizures were noted in 12% of patients, infantile spasms were reported in 8%, and myoclonic seizures were observed in 4%. Patients with Lennox-Gastaut syndrome have been reported.

Seizure control was achieved in 40-70% of patients. Some patients with partial seizures had very localized dysplastic lesions on neuroimaging that showed the typical localized, almost continuous, spike activity using electroencephalography (EEG).

Approximately one half to two thirds of patients have mental retardation (ie, intelligence quotient [IQ] < 70). Chromosomal anomalies do not appear to increase the risk of mental retardation. Approximately 40% of patients with hypomelanosis of Ito have an IQ of less than 50, and fewer than one fourth have an IQ of more than 85.

Autistic behavior has been found in approximately 11% of patients with hypomelanosis of Ito. It may be associated with infantile spasms and other severe seizures. Similarly, the presence of mental retardation is linked with seizures (65%). Although the causal association of seizures and mental retardation or autism is attractive and present outside of HI, a common mechanism for both can be easily demonstrated (eg, patients with neuroblast migration and neuronal dysplasias).

HI is occasionally associated with hemimegalencephaly; however, more focal dysplastic lesions are also observed. Approximately one fourth of patients have a motor development delay. Hypotonia, which is usually accompanied by pes and genu valgus, is also a common finding.

Somatic hemihypertrophy, macrocephaly, and microcephaly may also be present (see below).

Brain tumors, including medulloblastoma and choroid plexus papilloma, are associated with hypomelanosis of Ito.

Other neurological problems include ataxic gait, sensory neuropathy, chronic distal spinal muscular atrophy, torticollis, auditory conduction defect, hyperactivity, and spina bifida occulta.

Patients with occipital lesions may have visual field defects but could represent sporadic associations.

Neuropathological studies demonstrate polymicrogyria, disarray of cortical lamination, heterotopic neurons in the white matter, and giant cells.

Ophthalmologic abnormalities

Approximately one fifth of patients present with ocular abnormalities.

Retinal pigment abnormalities are described as tessellated fundus, radial hypopigmented streaks, or geographic areas of hypopigmentation. Unilateral heterochromic iris with hypopigmentation of the cornea has also been described.

Other ophthalmologic changes include myopia, hyperopia, astigmatism, megalocornea, opaque corneas, scleral melanosis, strabismus, slow pupillary response, pupillary atrophy or irregularity, nonclosure of the upper eyelid, ptosis, symblepharon, optic atrophy, choroidal atrophy, microphthalmia, macrophthalmia, epicanthal folds, dacryostenosis, and nystagmus.

Musculoskeletal abnormalities

Musculoskeletal abnormalities are common. One fifth of patients have hemihypertrophy, usually ipsilateral-to-hypomelanotic lesions.

Arm and leg length discrepancy and scoliosis are reported.

Fingers may be abnormal, showing atrophy, syndactyly, polydactyly, clinodactyly, or bifid thumb.

Other limb anomalies include luxatio coxae (caused by hypoplastic femoral heads) and genu valgus.

Head and face anomalies

Facial malformations include hypertelorism, coarse facies, cleft lip and palate, bifid uvula, and nose and ear anomalies.

Macrocephaly, often associated with coarse facies, develops in 3-23% of patients.

In a study by Pascual-Castroviejo et al, microcephaly was described in 8% of patients.[9]

Delayed fontanelle closure and asymmetry of the head can be present.

Dental problems include imperfect teeth implantation, partial anodontia and dental dysplasia, defective enamel, and hamartomatous cuspids.

Cardiac anomalies

Genital and reproductive organ anomalies

Other types of abnormalities

  • Hepatomegaly
  • Segmental dilation of the colon
  • Diaphragmatic, umbilical, and inguinal hernia

Hypomelanosis of Ito is considered a cutaneous disease with multisystem involvement. It may be associated with the above findings and may also be associated with proteinuria, focal segmental glomerulosclerosis and end-stage renal disease.[11]

Malignant and benign tumors are associated with hypomelanosis of Ito. One patient study reported a mature cystic teratoma in the posterior mediastinum and a diploic epidermoid cyst of the parietal bone. Brain tumors may be present (see above); however, the benign tumors in patients with hypomelanosis of Ito are often associated with chromosomal anomalies.

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Causes

Several chromosomal abnormalities have been reported in hypomelanosis of Ito (see Pathophysiology), but the etiology remains elusive.

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Contributor Information and Disclosures
Author

Camila K Janniger, MD  Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Camila K Janniger, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

Marcio Sotero de Menezes, MD  Associate Professor, Department of Neurology, Division of Pediatric Neurology, Children's Hospital of Seattle, University of Washington School of Medicine

Marcio Sotero de Menezes, MD is a member of the following medical societies: American Academy of Neurology and American Epilepsy Society

Disclosure: Novartis Salary Speaking and teaching; Cyberonics Salary Speaking and teaching; Athena diagnostics Salary Speaking and teaching

Specialty Editor Board

Kevin P Connelly, DO  Clinical Assistant Professor, Department of Pediatrics, Division of General Pediatrics and Emergency Care, Virginia Commonwealth University School of Medicine; Medical Director, Paws for Health Pet Visitation Program of the Richmond SPCA; Pediatric Emergency Physician, Emergency Consultants Inc, Chippenham Medical Center

Kevin P Connelly, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Merrily P M Poth, MD  Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences

Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Department of Dermatology, Geisinger Medical Center

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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