Medscape is available in 5 Language Editions – Choose your Edition here.


Pediatric Hypomelanosis of Ito Workup

  • Author: Camila K Janniger, MD; Chief Editor: Dirk M Elston, MD  more...
Updated: Jun 24, 2016

Laboratory Studies

Chromosomal analysis

Blood karyotyping is indicated, especially when systemic abnormalities are present.

Fibroblast karyotyping (sampling the dark and light skin) can reveal mosaicism but is not mandatory for diagnosis.


Imaging Studies

Neuroradiological abnormalities are reported in at least one third of the patients. Because many of the lesions are dysplastic or neuroblastic migration abnormalities, MRI is more useful than CT scanning.

Increase in the T2 signal of white matter is one of the most common findings. White matter abnormalities are somewhat predictive of a poor neurological outcome.

Neuroblast migration includes heterotopia, pachygyria, and polymicrogyria. Heterotopia may be observed at the level of the basal ganglia or as a periventricular band. Some of the dysplastic lesions may be localized, and hemimegalencephaly is also visualized.

Cerebral atrophy can be unilateral or generalized. Cases of cerebral hemiatrophy and porencephaly are often associated with a history of perinatal hypoxia or low birth weight.

Other rare imaging associations include the following:

  • Noncommunicating hydrocephalus
  • Megacisterna magna
  • Arteriovenous malformation
  • Cerebellar hypoplasia (hemispheres and vermis)
  • Brainstem hypoplasia
  • Brain tumors: MRI rarely reveals brain tumors; thus, patients occasionally have abnormal MRI findings but are neurologically healthy.

Brain imaging in patients with hypomelanosis of Ito (HI) and medically refractory epilepsy: The area that generates seizures (zone of ictal onset) should be found using a prolonged video-EEG, single-photon emission computed tomography (SPECT) or positron emission tomography (PET), and high-resolution MRI. If resective epilepsy surgery is a serious consideration after the preliminary tests are done (video-EEG, SPECT or PET) and the zone of ictal onset could not be determined, the patient may need to undergo invasive EEG monitoring with subdural grids or strips.

Other imaging tests

Musculoskeletal abnormalities often require radiography for proper quantification. A CT scan of the chest may be necessary when mediastinal tumors are investigated.

Abdominal ultrasonography may be required for diagnosis of genitourinary anomalies such as single kidney and urethral duplication.


Other Tests

In patients with seizures, an EEG is indicated to show focal discharges and slowing.

Most patients with cardiac anomalies require an ECG.

Perform a slit-lamp examination in patients with ophthalmologic abnormalities.



Biopsies of affected and nonaffected skin are sometimes indicated.

In select patients with cardiac anomalies, cardiac catheterization is recommended for proper diagnosis.


Histologic Findings

Dihydroxyphenylalanine (DOPA) staining of the skin may reveal decreased size and number of melanosomes in hypopigmented areas. The melanocytes may be smaller and fewer, and their dendrites are short and sparse. Melanin incontinence (ie, melanin is absent in the epidermis but present in the deeper dermis) is not observed in patients with hypomelanosis of Ito. Histopathological alterations are not always typical; normal histology findings have been described in some cases. Neuropathological studies demonstrate polymicrogyria, disarray of cortical lamination, and heterotopic neurons in the white matter and giant cells.

Ultrastructural cutaneous studies may reveal normal-appearing basal and malpighian keratinocytes but a lack of melanosomes in the malpighian cells.[7] Melanosomes are dramatically reduced in the basal keratinocytes and appear small, single, or clustered and surrounded by a membrane. Melanocytic degeneration may be evident, and dendritic melanocytes contain various stages of nonmelanized premelanosome (stage II), partially melanized premelanosome (stage III), and, rarely, stage IV melanosomes. Unmyelinated axons of nerve-containing melanosomes may be seen at the dermoepidermal junction. Abnormal nerve termination has been observed in close relationship with basal keratinocytes, degenerated melanocytes, premelanosomes, and Langerhans cells.

Contributor Information and Disclosures

Camila K Janniger, MD Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, Rutgers New Jersey Medical School

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

Disclosure: Nothing to disclose.


Marcio Sotero de Menezes, MD Clinical Associate Professor, Department of Neurology, Division of Pediatric Neurology, Seattle Children's Hospital, University of Washington School of Medicine; Director, Pediatric Neuroscience Center and Genetic Epilepsy Clinic, Swedish Neuroscience Institute

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

Disclosure: Received salary from Novartis for speaking and teaching; Received salary from Cyberonics for speaking and teaching; Received salary from Athena diagnostics for speaking and teaching.

Specialty Editor Board

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 of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

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

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

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

Disclosure: Nothing to disclose.

Additional Contributors

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, American Osteopathic Association

Disclosure: Nothing to disclose.

  1. Ito M. A singular case of naevus depigmentosus systematicus bilateralis. Jpn J Dermatol. 1951. 61:31-2.

  2. Hamada T, Saito T, Sugai T, Morita Y. "Incontinentia pigmenti achromians (Ito)". Arch Dermatol. 1967 Dec. 96(6):673-6. [Medline].

  3. Pascual-Castroviejo I, Lopez-Rodriguez L, de la Cruz Medina M, Salamanca-Maesso C, Roche Herrero C. Hypomelanosis of Ito. Neurological complications in 34 cases. Can J Neurol Sci. 1988 May. 15(2):124-9. [Medline].

  4. Ruiz-Maldonado R, Toussaint S, Tamayo L, Laterza A, del Castillo V. Hypomelanosis of Ito: diagnostic criteria and report of 41 cases. Pediatr Dermatol. 1992 Mar. 9(1):1-10. [Medline].

  5. Sybert VP. Hypomelanosis of Ito: a description, not a diagnosis. J Invest Dermatol. 1994 Nov. 103(5 Suppl):141S-143S. [Medline].

  6. Ponti G, Pellacani G, Tomasi A, Percesepe A, Guarneri C, Guerra A, et al. Hypomelanosis of Ito with a trisomy 2 mosaicism: a case report. J Med Case Rep. 2014 Oct 9. 8(1):333. [Medline].

  7. Palungwachira P, Palungwachira P. Incontinentia pigmenti achromians of Ito: an ultrastructural study. J Med Assoc Thai. 2006 Feb. 89(2):253-7. [Medline].

  8. Parisi L, Di Filippo T, Roccella M. Hypomelanosis of Ito: neurological and psychiatric pictures in developmental age. Minerva Pediatr. 2012 Feb. 64(1):65-70. [Medline].

  9. Okanari K, Miyahara H, Itoh M, Takahashi A, Aizaki K, Nakagawa E, et al. Hemimegalencephaly in a Patient With Coexisting Trisomy 21 and Hypomelanosis of Ito. J Child Neurol. 2012 Dec 23. [Medline].

  10. Degerliyurt A, Kantar A, Ceylaner S, Aysun S. Hypomelanosis of Ito and Sturge-Weber Syndrome Without Facial Nevus: An Association or a New Syndrome?. Pediatr Neurol. 2009 May. 40(5):395-397. [Medline].

  11. Inoue M, Fukuda M, Ishii E, Sayama K. Linear Leukoplakia and Central Nervous System Lesions: A Clinical Clue to the Diagnosis of Hypomelanosis of Ito. J Pediatr. 2015 Sep. 167 (3):771-771.e1. [Medline].

  12. Souza PV, Pinto WB, Calente FG, Burlin S, Pedroso JL, Oliveira AS, et al. Hypomelanosis of Ito presenting with adult-onset dementia and marked enlarged Virchow-Robin spaces. Arq Neuropsiquiatr. 2015 Apr. 73 (4):366-8. [Medline].

  13. Glover MT, Brett EM, Atherton DJ. Hypomelanosis of Ito: spectrum of the disease. J Pediatr. 1989 Jul. 115(1):75-80. [Medline].

  14. Pascual-Castroviejo I, Roche C, Martinez-Bermejo A, et al. Hypomelanosis of ITO. A study of 76 infantile cases. Brain Dev. 1998 Jan. 20(1):36-43. [Medline].

  15. Park JM, Kim HJ, Kim T, Chae HW, Kim DH, Lee MG. Sexual precocity in hypomelanosis of Ito: mosaicism-associated case report and literature review. Int J Dermatol. 2011 Feb. 50(2):168-74. [Medline].

  16. Pavone V, Signorelli SS, Praticò AD, Corsello G, Savasta S, Falsaperla R, et al. Total Hemi-overgrowth in Pigmentary Mosaicism of the (Hypomelanosis of) Ito Type: Eight Case Reports. Medicine (Baltimore). 2016 Mar. 95 (10):e2705. [Medline].

  17. Gatter N, Hoppe B, Nutzenadel F, Waldherr R, Querfeld U. A cutaneous disease with multisystem involvement: hypomelanosis of Ito may be associated with proteinuria, focal segmental glomerulosclerosis and end-stage renal disease. Nephrol Dial Transplant. 2007 Mar 8. [Medline].

  18. Tragardh M, Thomsen CR, Thorninger R, Moller-Madsen B. Hypomelanosis of Ito presenting with pediatric orthopedic issues: a case report. J Med Case Rep. 2014 May 19. 8:156. [Medline]. [Full Text].

  19. Jozwiak S, Schwartz RA, Janniger CK, Bielicka-Cymerman J. Usefulness of diagnostic criteria of tuberous sclerosis complex in pediatric patients. J Child Neurol. 2000 Oct. 15(10):652-9. [Medline].

  20. Sybert VP, Pagon RA, Donlan M, Bradley CM. Pigmentary abnormalities and mosaicism for chromosomal aberration: association with clinical features similar to hypomelanosis of Ito. J Pediatr. 1990 Apr. 116(4):581-6. [Medline].

  21. Rosman NP. Incontinentia Pigmenti. Gomez MR, ed. Neurocutaneous Diseases: A Practical Approach. Boston: Butterworths; 1987. 294-300.

  22. Huggins RH, Schwartz RA, Janniger CK. Vitiligo. Acta Dermatovenerol Alp Panonica Adriat. 2005 Dec. 14(4):137-42, 144-5. [Medline].

  23. Huggins RH, Janusz CA, Schwartz RA. Vitiligo: a sign of systemic disease. Indian J Dermatol Venereol Leprol. 2006 Jan-Feb. 72(1):68-71. [Medline].

  24. Jadotte YT, Janniger CK. Pityriasis alba revisited: perspectives on an enigmatic disorder of childhood. Cutis. 2011 Feb. 87(2):66-72. [Medline].

  25. Zhu W, Gao J. The use of botanical extracts as topical skin-lightening agents for the improvement of skin pigmentation disorders. J Investig Dermatol Symp Proc. 2008 Apr. 13(1):20-4. [Medline].

  26. Urban J, Toruniowa B, Janniger CK, Czelej D, Schwartz RA. Incontinentia pigmenti (Bloch-Sulzberger syndrome): multisystem disease observed in two generations. Cutis. 1996 Nov. 58(5):329-36. [Medline].

Hypomelanosis of Ito on the torso.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.