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Dermatology > DISEASES OF PIGMENTATION
Hypomelanosis of Ito
Article Last Updated: Jan 25, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: John Ratz, MD, MBA, Staff Dermatologist, Mohs Surgeon, Center for Dermatology and Skin Surgery, Inc
John Ratz is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Micrographic Surgery and Cutaneous Oncology, American College of Physicians, American Society for Dermatologic Surgery, American Society for Laser Medicine and Surgery, International Society for Dermatologic Surgery, and Southern Medical Association
Coauthor(s):
Ned Gross, MD, President, Central Piedmont Dermatology
Editors: Sungnack Lee, MD, Vice President of Medical Affairs, Professor, Department of Dermatology, Ajou University School of Medicine, Korea; Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center; Christen M Mowad, MD, Assistant Professor, Department of Dermatology, Geisinger Medical Center; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Author and Editor Disclosure
Synonyms and related keywords:
HI, incontinentia pigmenti achromians, hypopigmented whorls of skin along Blaschko lines
Background
Hypomelanosis of Ito (HI) is a syndrome with hypopigmented whorls of skin along the Blaschko lines. The old name, incontinentia pigmenti achromians, implies an association with incontinentia pigmenti (IP) and was probably used because HI 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 HI; however, no consensus exists about the identity of the HI gene. The human genome project investigators report the HI locus is a balanced translocation of Xp21.2, the location of the COL5A1 gene in a patient with Ehlers-Danlos syndrome. One report of HI involves a pair of monozygotic twins in which only one twin is affected. The Xp11 locus had been previously described in sporadic IP, but recent authors believe that this mosaic mutation is truly HI. See the Online Mendelian Inheritance of Man Web site for full details.
Frequency
International
HI is rare.
Mortality/Morbidity
Death is rare; this disease has only cutaneous involvement. Morbidity depends on severity of the associated abnormality such as seizures.
Race
No clear racial predilection is reported.
Sex
HI is 1.5-2.5 times more common in women than in men.
Age
HI 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.
History
- Patients 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 HI 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.
- The literature contains reviews, mostly from neurology departments, that report rates of HI-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 Images 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 HI.
Causes
Chromosomal mosaicism and sporadic mutations are the causes, but the identity of a specific gene has not been confirmed.
- Probably, several gene abnormalities cause the phenotype that is recognized as HI.
- For this reason, some authors believe that HI is a symptom and that it may not be a distinct disease.
- Some believe that HI results in the somatic mosaicism of the IP 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 IP and HI are distinct diseases with separate gene loci: Xp28 for IP and 9q33-ter, 15q11, Xp11, and Xp21.2 for HI.
- The previously described sporadic IP gene at Xp11 is now believed to be related to HI.
Other Problems to be Considered
Fourth stage of incontinentia pigmenti
Linear and whorled nevoid hypermelanosis
Nevus depigmentus
Lab Studies
- Only history taking and physical examination with special attention to the neurologic and ophthalmologic findings are necessary to detect associated abnormalities.
- Consider genetic and/or chromosomal testing; these tests 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 head should be performed in those with neurologic symptoms.
- Skeletal radiography should be performed in those with apparent bony abnormalities.
Other Tests
- Perform EEG in those with seizure disorders.
- Perform electromyelography (EMG) in those with hypotonia.
Histologic Findings
The number of melanocytes is decreased, and the amount of melanin in hypopigmented areas is decreased.
Medical Care
- No treatment is administered for the cutaneous findings.
- Cover-up makeup can be used if the patient desires it.
- 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 in regard to the associated surgical problems, as the physical examination findings indicate.
Consultations
- Consult a genetic counselor.
- Consult a neurologist, psychiatrist, orthopedic specialist, dentist, or ophthalmologist, as the features of the history and physical examination indicate.
Activity
No limitations on activity are required.
Further Inpatient Care
- No further inpatient care is needed, except that indicated for the associated abnormalities.
Further Outpatient Care
- Routine outpatient care is sufficient, except when associated abnormalities require additional care.
Deterrence/Prevention
- Genetics counseling may aid in the prevention of HI.
Complications
- Complications may occur as a result of associated abnormalities.
Prognosis
- The prognosis is determined by the associated abnormalities.
- The prognosis is excellent for the cutaneous findings.
Patient Education
- Genetic counseling may be recommended.
- However, the risk of HI transmission is considered low, except when X-linked mutations are present in female patients.
Medical/Legal Pitfalls
- Patients should undergo a thorough examination to identify any associated abnormalities and possible treatments.
- Although the risk of having more affected children is low, genetic counseling may be useful.
| Media file 2:
Hypomelanosis of Ito highlighted with a Wood lamp. |
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Media type: Photo
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- Donnai D, Read AP, McKeown C, Andrews T. Hypomelanosis of Ito: a manifestation of mosaicism or chimerism. J Med Genet. Dec 1988;25(12):809-18. [Medline].
- Fritz B, Kuster W, Orstavik KH, et al. Pigmentary mosaicism in hypomelanosis of Ito. Further evidence for functional disomy of Xp. Hum Genet. Oct 1998;103(4):441-9. [Medline].
- Glover MT, Brett EM, Atherton DJ. Hypomelanosis of Ito: spectrum of the disease. J Pediatr. Jul 1989;115(1):75-80. [Medline].
- Hatchwell E. Hypomelanosis of Ito and X;autosome translocations: a unifying hypothesis. J Med Genet. Mar 1996;33(3):177-83. [Medline].
- McKusic VA. Online Mendelian Inheritance in Man (OMIM) [serial online]. 2000;Available at: http://w3.ncbi.nlm.nih.gov/Omim/. [Full Text].
- Nehal KS, PeBenito R, Orlow SJ. Analysis of 54 cases of hypopigmentation and hyperpigmentation along the lines of Blaschko. Arch Dermatol. Oct 1996;132(10):1167-70. [Medline].
- Pascual-Castroviejo I, Roche C, Martinez-Bermejo A, et al. Hypomelanosis of ITO. A study of 76 infantile cases. Brain Dev. Jan 1998;20(1):36-43. [Medline].
Hypomelanosis of Ito excerpt Article Last Updated: Jan 25, 2007
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