Congenital Patterned Leukodermas 

  • Author: Raymond E Boissy, PhD; Chief Editor: William D James, MD   more...
 
Updated: Jan 13, 2012
 

Background

The following congenital hypopigmentary diseases result from a failure of pigment cells (melanocytes) in the skin, eyes, and/or ears to become completely or partially established in their target sites during embryogenesis:

Patients with these congenital patterned leukodermas may also present with extrapigmentary findings consisting of megacolon and musculoskeletal defects of the face and upper trunk.

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Pathophysiology

The unifying abnormality of these congenital patterned leukodermas is a complete or partial absence of melanocytes in the skin and hair. Mutations in genes that regulate the multistep process of commitment of neural crest cells to a differentiated cell type (primarily the melanocyte) are the basis for these diseases. These mutations result in a failure of melanocytes to reach their normal destinations in developing skin, hair, eyes, and ears during embryogenesis.[1, 2, 3, 4]

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Epidemiology

Frequency

International

The approximate prevalences of the listed congenital patterned leukodermas are as follows:

  • Waardenburg syndrome (types I, II, and III) - 1 case per 15,000 population
  • Apert syndrome - 1 case per 65,000 population
  • Pfeiffer syndrome - Unknown (rare)
  • Jackson-Weiss syndrome - Unknown (rare)
  • Crouzon syndrome - 1 case per 25,000 population
  • Waardenburg syndrome type IV (Hirschsprung syndrome) - 1 case per 5000 population
  • Piebaldism – Unknown (rare)

Mortality/Morbidity

In the congenital patterned leukodermas, an absence of protective pigment in the skin results in increased sensitivity to solar irradiation. Affected individuals may be at increased risk of developing skin cancers. Sensorineural deafness can be extensive in patients with Waardenburg syndromes and Hirschsprung syndrome but is usually minimal or absent in those with Apert, Pfeiffer, Jackson-Weiss, or Crouzon syndromes. Persons with piebaldism only rarely have sensorineural deafness. Visual acuity does not appear to be impaired in any of the syndromes.

Race

All races appear to be equally affected by the associated mutations in congenital patterned leukodermas.

Sex

The prevalence of these congenital patterned leukodermas is equal for males and females.

Age

All of these congenital patterned leukodermas are present at birth.

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Contributor Information and Disclosures
Author

Raymond E Boissy, PhD  Director of Basic Science Research, Professor, Departments of Dermatology and Cell Biology, University of Cincinnati College of Medicine

Raymond E Boissy, PhD is a member of the following medical societies: Sigma Xi

Disclosure: University of Cincinnati None None

Coauthor(s)

Steven Hoath, MD  Director of Skin Sciences Institute, Professor of Pediatrics, Department of Pediatrics, University of Cincinnati College of Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Kathryn Schwarzenberger, MD  Associate Professor of Medicine, Division of Dermatology, University of Vermont College of Medicine; Consulting Staff, Division of Dermatology, Fletcher Allen Health Care

Kathryn Schwarzenberger, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Contact Dermatitis Society, American Dermatological Association, Dermatology Foundation, Medical Dermatology Society, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Van Perry, MD  Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery

Disclosure: Nothing to disclose.

Joel M Gelfand, MD, MSCE  Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania

Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology

Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

William D James, MD  Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: Elsevier Royalty Other

References

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  14. Park WJ, Meyers GA, Li X, et al. Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic heterogeneity and phenotypic variability. Hum Mol Genet. Jul 1995;4(7):1229-33. [Medline].

  15. Park WJ, Theda C, Maestri NE, et al. Analysis of phenotypic features and FGFR2 mutations in Apert syndrome. Am J Hum Genet. Aug 1995;57(2):321-8. [Medline].

  16. Giebel LB, Spritz RA. Mutation of the KIT (mast/stem cell growth factor receptor) protooncogene in human piebaldism. Proc Natl Acad Sci U S A. Oct 1 1991;88(19):8696-9. [Medline].

  17. Thomas I, Kihiczak GG, Fox MD, Janniger CK, Schwartz RA. Piebaldism: an update. Int J Dermatol. Oct 2004;43(10):716-9. [Medline].

  18. Mollet I, Ongenae K, Naeyaert JM. Origin, clinical presentation, and diagnosis of hypomelanotic skin disorders. Dermatol Clin. Jul 2007;25(3):363-71, ix. [Medline].

  19. Puffenberger EG, Kauffman ER, Bolk S, et al. Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22. Hum Mol Genet. Aug 1994;3(8):1217-25. [Medline].

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