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Piebaldism

  • Author: Camila K Janniger, MD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Jun 21, 2016
 

Background

Piebaldism is a rare autosomal dominant disorder of melanocyte development characterized by a congenital white forelock and multiple symmetrical hypopigmented or depigmented macules. This striking phenotype of depigmented patches of skin and hair has been observed throughout history, with the first descriptions dating to early Egyptian, Greek, and Roman writings. Generation after generation demonstrated a distinctive predictable familial mark—a white forelock. Families have sometimes been known for this mark of distinction, carrying such surnames as Whitlock, Horlick, and Blaylock. Note the image below.

Distinguished physician with mark of distinction, Distinguished physician with mark of distinction, a white forelock that his father and grandfather also shared.

The word piebald itself has been attributed to a combination of the "pie" in the magpie (a bird of black and white plumage) and the "bald" of the bald eagle (the United States' national bird, which has a white feathered head).

Piebaldism is due to an absence of melanocytes in affected skin and hair follicles as a result of mutations of the KIT proto-oncogene.[1] As of a 2001 review by Richards et al, 14 point mutations, 9 deletions, 2 nucleotide splice mutations, and 3 insertions of the KIT gene were believed to be mutations causing piebaldism.[2] The severity of phenotypic expression in piebaldism correlates with the site of the mutation within the KIT gene. The most severe mutations seem to be dominant negative missense mutations of the intracellular tyrosine kinase domain, whereas mild piebaldism appears related to mutations occurring in the amino terminal extracellular ligand-binding domain with resultant haplo insufficiency.

Most piebald patients have the above-described mutation of the KIT gene encoding a tyrosine kinase receptor involved in pigment cell development.[3] The white hair and patches of such patients are completely formed at birth and do not usually expand thereafter. However, 2 novel cases of piebaldism were described in which both mother and daughter had a novel Val620Ala mutation in their KIT gene and showed progressive depigmentation. These findings are consistent with the hypothesis that progressive piebaldism might result from digenic inheritance of the KIT (V620A) mutation that causes piebaldism and a second, unknown locus that causes progressive depigmentation.[4]

Piebaldism is one of the cutaneous signs of Waardenburg syndrome, along with heterochromia of the irides, lateral displacement of inner canthi, and deafness.[5]

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Pathophysiology

Piebaldism is an autosomal dominant genetic disorder of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. Piebaldism results from mutations of the KIT proto-oncogene, which encodes the cell surface receptor transmembrane tyrosine kinase for an embryonic growth factor, steel factor.[6] Several pathologic mutations of the KIT gene now have been identified in different patients with piebaldism.[7] Correlation of these mutations with the associated piebald phenotypes has led to the recognition of a hierarchy of 3 classes of mutations that result in a graded series of piebald phenotypes. KIT mutations in the vicinity of codon 620 lead to the usual phenotype of static piebaldism. Mutations of the KIT proto-oncogene produce variations in phenotype in relation to the site of the KIT gene mutation.

In an analysis of 26 unrelated patients with piebaldismlike hypopigmentation (ie, 17 typical patients, 5 patients with atypical clinical features or family histories, and 4 patients with other disorders that involve white spotting), novel pathologic mutations or deletions of the KIT gene were observed in 10 (59%) of the typical patients and in 2 (40%) of the atypical patients. Overall, pathologic KIT gene mutations were identified in 21 (75%) of 28 unrelated patients with typical piebaldism. Patients without apparent KIT mutations had no apparent abnormalities of the gene encoding steel factor itself; however, genetic linkage analyses in 2 of these families implied linkage of the piebald phenotype to KIT. Thus, most patients with typical piebaldism seem to have abnormalities of the KIT gene. A complex network of interacting genes regulates embryonic melanocyte development.

Piebaldism almost always has a static course. Genetic analysis of a mother and daughter with progressive piebaldism revealed a novel Val620Ala (1859T>C) mutation in the KIT gene. This KIT mutation and others of the tyrosine kinase domain affect the intracellular tyrosine kinase domain and may imply a severe phenotype.[8] This is a newly described phenotype with melanocyte instability leading to advancing loss of pigmentation and the progressive appearance of the hyperpigmented macules.

A South African girl of Xhosa ancestry with severe piebaldism and profound congenital sensorineural deafness had a novel missense substitution at a highly conserved residue in the intracellular kinase domain of the KIT proto-oncogene, R796G. Although auditory anomalies in mice with dominant white spotting due to KIT mutations may occur, deafness is not typical in human piebaldism. Thus, sensorineural deafness extends considerably the phenotypic range of piebaldism due to KIT gene mutation in humans and strengthens the clinical similarity between piebaldism and the various forms of Waardenburg syndrome. A novel mutation of the KIT gene was described in a Chinese family with piebaldism.[9]

Manipulation of the mouse genome may be an important approach for studying gene function and establishing human disease models.[10] Mouse mutants generated and screened for dominant mutations yielded several mice with fur color abnormalities. One causes a phenotype similar to dominant-white spotting (W) allele mutants. This strain may serve as a new disease model of human piebaldism.

Genetic factors determining piebaldism in Italian Holstein and Italian Simmental cattle breeds were studied.[11] Variability in the microphthalmia-associated transcription factor gene explained the differences between spotted and nonspotted phenotypes, although other genetic factors were also important.

A splicing mutation, producing the deletion of exon 17 of KIT, and co-segregated it with 2 phenotypes of the severe form of piebaldism and auburn hair color was documented in a Chinese Han family.[12]

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Prognosis

Piebaldism is a benign disorder. However, patients are at risk for actinic complications related to absence of cutaneous melanocytes. Although spontaneous repigmentation in an infant with piebaldism has been described, it is most unusual.[13]

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Patient Education

Educate patients about the genetic transmission of the disorder.

Educate patients about use of sunscreens, sunprotective measures (eg, wide-brimmed hat, long-sleeved shirts, long pants), sun avoidance during peak hours of ultraviolet exposure during the day, and self-examinations because recurrent sun damage may result in an increased risk of cutaneous malignancy.

Patients who are self-conscious about the appearance of their skin may benefit from use of a camouflage cover-up, such as Dermablend or other similar camouflage measures.

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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, 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.

Coauthor(s)

Michael D Fox, MD Attending Physician, Department of Emergency Medicine, Marin General Hospital

Michael D Fox, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Geriatrics Society, American Academy of Family Physicians, California Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

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

Albert C Yan, MD Section Chief, Associate Professor, Department of Pediatrics, Section of Dermatology, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine

Albert C Yan, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology, Society for Pediatric Dermatology, American Academy of Pediatrics

Disclosure: Nothing to disclose.

References
  1. Ezoe K, Holmes SA, Ho L, et al. Novel mutations and deletions of the KIT (steel factor receptor) gene in human piebaldism. Am J Hum Genet. 1995 Jan. 56(1):58-66. [Medline].

  2. Richards KA, Fukai K, Oiso N, Paller AS. A novel KIT mutation results in piebaldism with progressive depigmentation. J Am Acad Dermatol. 2001 Feb. 44(2):288-92. [Medline].

  3. Tosaki H, Kunisada T, Motohashi T, Aoki H, Yoshida H, Kitajima Y. Mice transgenic for Kit(V620A): recapitulation of piebaldism but not progressive depigmentation seen in humans with this mutation. J Invest Dermatol. 2006 May. 126(5):1111-8. [Medline].

  4. Spritz RA. "Out, damned spot!". J Invest Dermatol. 2006 May. 126(5):949-51. [Medline].

  5. Jan IA, Stroedter L, Haq AU, Din ZU. Association of Shah-Waardenburgh syndrome: a review of 6 cases. J Pediatr Surg. 2008 Apr. 43(4):744-7. [Medline].

  6. Nomura K, Hatayama I, Narita T, Kaneko T, Shiraishi M. A novel KIT gene missense mutation in a Japanese family with piebaldism. J Invest Dermatol. 1998 Aug. 111(2):337-8. [Medline].

  7. Murakami T, Fukai K, Oiso N. New KIT mutations in patients with piebaldism. J Dermatol Sci. 2004 Jun. 35(1):29-33. [Medline].

  8. Kerkeni E, Boubaker S, Sfar S, Bizid M, Besbes H, Bouaziz S, et al. Molecular characterization of piebaldism in a Tunisian family. Pathol Biol (Paris). 2015 Jun. 63 (3):113-6. [Medline].

  9. Xu XH, Ma L, Weng L, Xing H. A novel mutation of KIT gene results in piebaldism in a Chinese family. J Eur Acad Dermatol Venereol. 2014 Sep 8. [Medline].

  10. Ruan HB, Zhang N, Gao X. Identification of a novel point mutation of mouse proto-oncogene c-kit through N-ethyl-N-nitrosourea mutagenesis. Genetics. 2005 Feb. 169(2):819-31. [Medline].

  11. Fontanesi L, Scotti E, Russo V. Haplotype variability in the bovine MITF gene and association with piebaldism in Holstein and Simmental cattle breeds. Anim Genet. 2012 Jun. 43(3):250-6. [Medline].

  12. Yang YJ, Zhao R, He XY, Li LP, Wang KW, Zhao L, et al. A Novel Splicing Mutation of KIT Results in Piebaldism and Auburn Hair Color in a Chinese Family. Biomed Res Int. 2013. 2013:689756. [Medline]. [Full Text].

  13. Frances L, Betlloch I, Leiva-Salinas M, Silvestre JF. Spontaneous repigmentation in an infant with piebaldism. Int J Dermatol. 2015 Jun. 54 (6):e244-6. [Medline].

  14. Chow RK, Stewart WD, Ho VC. Graft-versus-host reaction affecting lesional skin but not normal skin in a patient with piebaldism. Br J Dermatol. 1996 Jan. 134(1):134-7. [Medline].

  15. Matsunaga H, Tanioka M, Utani A, Miyachi Y. Familial case of piebaldism with regression of white forelock. Clin Exp Dermatol. 2008 Jul. 33(4):511-2. [Medline].

  16. Grob A, Grekin S. Piebaldism in children. Cutis. 2016 Feb. 97 (2):90-2. [Medline].

  17. Desch LW. White forelock could be early sign of tuberous sclerosis. Arch Pediatr Adolesc Med. 1996 Jun. 150(6):651-2. [Medline].

  18. Tamayo ML, Gelvez N, Rodriguez M, Florez S, Varon C, Medina D, et al. Screening program for Waardenburg syndrome in Colombia: clinical definition and phenotypic variability. Am J Med Genet A. 2008 Apr 15. 146A(8):1026-31. [Medline].

  19. Tammaro A, Parisella FR, Colapietra D, Romano I, Persechino S. A case of piebaldism in a two-year-old female infant. G Ital Dermatol Venereol. 2016 Apr. 107 (2):208-9. [Medline].

  20. Duarte AF, Mota A, Baudrier T, Morais P, Santos A, Cerqueira R, et al. Piebaldism and neurofibromatosis type 1: family report. Dermatol Online J. 2010 Jan 15. 16(1):11. [Medline].

  21. Spritz R. Letter: Misdiagnosis of "neurofibromatosis" in patients with piebaldism. Dermatol Online J. 2011 Nov 15. 17(11):13. [Medline].

  22. Stevens CA, Chiang PW, Messiaen LM. Café-au-lait macules and intertriginous freckling in piebaldism: Clinical overlap with neurofibromatosis type 1 and Legius syndrome. Am J Med Genet A. 2012 May. 158A(5):1195-9. [Medline].

  23. Sleiman R, Kurban M, Succaria F, Abbas O. Poliosis circumscripta: Overview and underlying causes. J Am Acad Dermatol. 2013 Jul 12. [Medline].

  24. Park SY, Kim HJ, Ahn SK. Piebaldism with neurofibromatosis type I: a familial case. Ann Dermatol. 2014 Apr. 26(2):264-6. [Medline]. [Full Text].

  25. Njoo MD, Nieuweboer-Krobotova L, Westerhof W. Repigmentation of leucodermic defects in piebaldism by dermabrasion and thin split-thickness skin grafting in combination with minigrafting. Br J Dermatol. 1998 Nov. 139(5):829-33. [Medline].

  26. Garg T, Khaitan BK, Manchanda Y. Autologous punch grafting for repigmentation in piebaldism. J Dermatol. 2003 Nov. 30(11):849-50. [Medline].

  27. Komen L, Vrijman C, Tjin EP, Krebbers G, de Rie MA, Luiten RM, et al. Autologous cell suspension transplantation using a cell extraction device in segmental vitiligo and piebaldism patients: A randomized controlled pilot study. J Am Acad Dermatol. 2015 Jul. 73 (1):170-2. [Medline].

  28. Goh BK, Chua XM, Chong KL, de Mil M, van Geel NA. Simplified cellular grafting for treatment of vitiligo and piebaldism: the "6-well plate" technique. Dermatol Surg. 2010 Feb. 36(2):203-7. [Medline].

  29. Falabella R, Barona M, Escobar C, Borrero I, Arrunategui A. Surgical combination therapy for vitiligo and piebaldism. Dermatol Surg. 1995 Oct. 21(10):852-7. [Medline].

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

 
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Distinguished physician with mark of distinction, a white forelock that his father and grandfather also shared.
 
 
 
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