Find information on thousands of medical conditions and prescription drugs.

Incontinentia pigmenti

Incontinentia Pigmenti (IP) is a genetic disorder that affects the skin, hair, teeth, and nails. It is also known as Bloch Sulzberger syndrome, Bloch Siemens syndrome, melanoblastosis cutis and naevus pigmentosus systematicus. more...

ICF syndrome
Ichthyosis vulgaris
Imperforate anus
Inborn error of metabolism
Incontinentia pigmenti
Infant respiratory...
Infantile spinal muscular...
Infective endocarditis
Inflammatory breast cancer
Inguinal hernia
Interstitial cystitis
Iodine deficiency
Irritable bowel syndrome

The skin lesions evolve through characteristic stages:

  1. blistering (from birth to about four months of age),
  2. a wart-like rash (for several months),
  3. swirling macular hyperpigmentation (from about six months of age into adulthood), followed by
  4. linear hypopigmentation.

Alopecia, hypodontia, abnormal tooth shape, and dystrophic nails are observed. Some patients have retinal vascular abnormalities predisposing to retinal detachment in early childhood. Cognitive delays/mental retardation are occasionally seen.

The diagnosis of IP is established by clinical findings and occasionally by corroborative skin biopsy. Molecular genetic testing of the IKBKG gene (chromosomal locus Xq28) reveals disease-causing mutations in about 80% of probands. Such testing is available clinically. In addition, females with IP have skewed X-chromosome inactivation; testing for this can be used to support the diagnosis.

IP is inherited in an X-linked dominant manner. IP is lethal in most, but not all, males. A female with IP may have inherited the IKBKG mutation from either parent or have a new gene mutation. Parents may either be clinically affected or have germline mosaicism. Affected women have a 50% risk of transmitting the mutant IKBKG allele at conception; however, most affected male conceptuses miscarry. Thus, the expected ratio for liveborn children is 33% unaffected females, 33% affected females, and 33% unaffected males. Genetic counseling and prenatal testing is available.

This disorder was first reported by Bruno Bloch, a German dermatologist in 1926 and Marion Sulzberger, an American dermatologist in 1928.


[List your site here Free!]

Tumors and hypomelanosis of ito
From Archives of Pathology & Laboratory Medicine, 5/1/01 by Ruggieri, Martino

To the Editor.-We read with interest the article by Xu et al1 reporting on the occurrence of a primary meningeal rhabdomyosarcoma in a 15month-old boy with hypomelanosis of Ito (HI). The report is intriguing because of the rarity of the tumor per se and its association to HI. However, in light of the most recent clinical and genetic studies on HI, we would like to add some comments on (1) the incidence of associated systemic features and current diagnostic criteria, (2) recent cytogenetic findings, and (3) its association with tumors.

The term hypomelanosis of Ito is applied to individuals with skin hypopigmentation along the lines of Blaschko.2,3 However, because of conflicting reports about the frequency of associated extracutaneous abnormalities (mostly of the central nervous, musculoskeletal, and ocular systems) and disagreement over terminology, HI still represents a controversial issue in the medical literature.2,3

One explanation for the discrepancy in figures for associated abnormalities could be that earlier studies were based on limited and biased cases. These reports tended to describe the most severely affected patients with multiple abnormal systemic features who were referred to tertiary care centers for diagnosis and management. Lower incidences (33% to 66%) of associated extracutaneous findings were demonstrated by dermatology and pediatric dermatology groups,4 while higher frequencies (80% to 94%) have been reported by neurology and pediatric neurology groups.5

Things are further complicated by current diagnostic criteria which are not sufficiently restricted, as highlighted by recent studies.2-4 In fact, according to the sine qua non criterion ("presence of skin hypopigmentation in linear streaks or patches involving more than two body segments"6) a significant number of individuals can be diagnosed as having HI because of the presence of diffuse or patchy, generalized or limited, linear or spotty skin depigmentation or hypopigmentation distributed along the lines of Blaschko, but also in many other configurations. In addition, 2 other criteria,6 precisely, involvement of the nervous or musculoskeletal systems (major criterion) or presence of other (unspecified) congenital malformations or chromosomal anomalies (minor criterion), are considered as additional features for making a diagnosis of HI. However, the association of nervous system or musculoskeletal abnormalities with linear or patchy pigmentary skin anomalies is encountered in many clinical conditions other than HI.7 These are probably some of the causes that contributed to generating confusion and to expanding the phenotype of HI by lumping together patients previously thought to have different conditions and combining under the same rubric several disorders of different etiologies. Notably, in the London Dysmorphology Database7 (a computerized catalog of dysmorphic-neurogenetic disorders), 65 different syndromes (including HI) are listed under the same entry "patchy depigmentation of skin."

A number of reports have claimed familial occurrence, supporting single-gene inheritance for HI, but none has been proved.2,3,8 Miscellaneous chromosomal abnormalities have been demonstrated in some but not all affected individuals and are currently classified into 2 groups3,9: (1) various mosaicism for almost any autosome or sex chromosomes and (2) nonmosaic balanced X;autosome translocations with breakpoints in the juxtacentromeric region of the X chromosome at Xp11 found so far in a limited group of girls with HI.9 Such mosaicism is generally not transmissible from one generation to the next, and this could explain the sporadic occurrence of the disorder. There could be some reasons for lack of demonstration of chromosomal mosaicism in all individuals with HI10: (1) most cytogenetic studies have been directed so far at peripheral lymphocytes or at cultured fibroblasts obtained from skin biopsies rather than at cultured keratinocytes or melanocytes (lines of Blaschko are epidermal not dermal), and (2) some genetic mosaicisms are too subtle to be detected by current techniques. Thus, despite current lack of a definitive genetic explanation, it has been suggested that HI is not a single condition, but a rather nonspecific manifestation (ie, a phenotype) of different chromosomal mosaicism and that the term hypomelanosis of Ito should now be dropped.2,3,9,10 Proposed changes to terminology, so far, include the terms pigmentary dysplasia, mosaic dyspigmentation, pigmentary mosaicism of the Ito type, or hypopigmentation along the lines of Blaschko to reflect the disease pathogenesis or recall the cutaneous patterns.9,10

A limited number of HI cases are associated with benign11-16 and malignant1,17-19 tumors (Table). When peripheral blood lymphocytes and tumor specimens have been searched for chromosomal abnormalities (as in 4 of the 9 reported cases), they were found (Table). We did not observe tumors in any of the 41 patients with HI (aged 2 to 40 years) seen at our institution, of whom 45% harbored chromosomal anomalies (unpublished data).20 Similar findings were recorded in the largest series reported to date.4-6,18 Notably, almost all reported tumors in HI (Table) share a common embryonal origin,1,11-13,15-17,19 in accordance to what was postulated by Xu et al.1 In addition, these tumors present during the first years of life, confirming that parents should be reassured that serious complications in HI, if present, are typically evident early in infancy.4

1. Xu F, De Las Casas LE, Dobbs LJ. Primary meningeal rhabdomyosarcoma in a child with hypomelanosis of Ito. Arch Pathol Lab Med. 2000;124:762-- 765.

2. Sybert V. Hypomelanosis of Ito: a description, not a diagnosis. J Invest Dermatol. 1994;103:1415-- 1435.

3. Kuster W, Konig A. Hypomelanosis of Ito: no

entity, but a cutaneous sign of mosaicism. Am J Med Genet. 1999;85:346-350.

4. Nehal KS, PeBenito R, Orlow SJ. Analysis of 54 cases of hypopigmentation and hyperpigmentation along the lines of Blaschko. Arch DermatoL 1996;132:1167-1170.

5. Pascual-Castroviejo I, Roche C, Martinez-Bermejo A, et al. Hypomelanosis of Ito: a study of 76 infantile cases. Brain Dev. 1998;20:36-43.

6. Ruiz-Maldonado R, Toussaint S, Tamayo L, Laterza A, Castillo VD. Hypomelanosis of Ito: diagnostic criteria and report of 41 cases. Pediatr Dermatol. 1992;9:1-10.

7. Winter RM, Baraitser M. The London Dysmorphology Database. Oxford, England: Oxford University Press; 2000.

8. Ruggieri M. Familial hypomelanosis of Ito: implications for genetic counselling. Am J Med Genet. 2000;95:82-84.

9. Hatchwell E. Hypomelanosis of Ito and X;autosome translocations: a unifying hypothesis. J Med Genet. 1996;33:177-183.

10. Moss C, Savin J. Dermatology and the New Genetics. Oxford, England: Blackwell Science; 1995: 3-35.

11. Browne RM, Byrne JPH. Dental dysplasia in incontinentia pigmenti achromians (Ito): an unusual form. Br Dent J. 1976;140:211-214.

12. Happle R, Vakilzadeh F Hamartomatous dental cusps in hypomelanosis of Ito. Clin Genet. 1982;21:65-68.

13. Ishikawa T, Kanayama M, Sugiyama K, et al. Hypomelanosis of Ito associated with benign tumours and chromosomal abnormalities: a neurocutaneous syndrome. Brain Dev. 1985;7:45-49.

14. Turleau C, Taillard F, Doussau de Bazignan M, et al. Hypomelanosis of Ito (incontinentia pigmenti achromians) and mosaicism for a microdeletion of 15q1. Hum Genet. 1986;74:165-187.

15. Steichen-Gersdorf E, Trawoger R, Duba HC, et al. Hypomelanosis of Ito in a girl with plexus papil(oma and translocation (X;17). Hum Genet. 1993; 90:611-613.

16. Zajac V, Kirchhoff T, Levy ER, et al. Characterisation of X;17(ql3) translocation breakpoints in a female patient with hypomelanosis of Ito and choroid plexus papilloma. Eur J Hum Genet. 1997; 5:61-68.

17. Tateno A, Sasaki S, Tsukimoto I, Mizuno K. A case of incontinentia pigmenti achromians with acute lymphatic leukemia. Shonika Rinsho. 1981; 34:831-835.

18. Steiner J, Adamsbaum C, Desguerres I, et al. Hypomelanosis of [to and brain abnormalities: MRI findings and literature review. Pediatr RadioL 1996; 26:763-768.

19. Oguma E, Aihara T, Shimanuki Y, et al. Hypomelanosis of Ito associated with neuroblastoma. Pediatr Radiol. 1996;26:273-275.

20. Ruggieri M, Pavone L. Hypomelanosis of Ito: clinical syndrome or just phenotype? J Child Neurol. 2000;15:635-644.


Institute of Bioimaging and

Pathophysiology of the Central Nervous System

National Research Council

Catania, Italy


Institute of Anatomic Pathology

University of Catania

Catania, Italy



Department of Paediatrics

University of Catania

Catania, Italy

Copyright College of American Pathologists May 2001
Provided by ProQuest Information and Learning Company. All rights Reserved

Return to Incontinentia pigmenti
Home Contact Resources Exchange Links ebay