eMedicine Specialties > Dermatology > Pediatric Diseases

Waardenburg Syndrome: Differential Diagnoses & Workup

Author: Lyubomir A Dourmishev, MD, PhD, Assistant Professor, Department of Dermatology, Medical University, Alexander's University Hospital, Bulgaria
Coauthor(s): Camila K Janniger, MD, Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, New Jersey Medical School
Contributor Information and Disclosures

Updated: Jun 2, 2009

Differential Diagnoses

Albinism
Piebaldism
Vitiligo
Vogt-Koyanagi-Harada Syndrome

Other Problems to Be Considered

  • Woolf syndrome (the association of albinismus circumscriptus and deafmutism without other features of Waardenburg syndrome): This entity consists of separated genetic defects with autosomal dominant inheritance; however, the distinguishing structural ophthalmologic abnormalities of dystopia canthorum, broad nasal root, and synophrys are not found in either piebaldism or Woolf syndrome.
  • Fisch syndrome (a distinct entity with early graying of the hair and congenital deafness)
  • Rozycki syndrome (autosomal recessive deafness associated with vitiligo)

Workup

Laboratory Studies

Waardenburg syndrome types 1 and 3 are most commonly associated with point mutations in PAX3, and type 2 is associated with MITF point mutations. Multiplex ligation-dependent probe amplification can be used to detect changes in targeted genes.18

Other Tests

  • Partington used the 3 interocular distances for determining the presence of dystopia cantorum. (The referent value between distance of the medial canthi of the eyelids and the length between the pupils was 0.6 mm.)
    • Between the inner canthal angles
    • The near papillary distance
    • Between the other canthal angles
  • Arias and Mota developed the W index for the diagnosis of lateral displacement of the inner canthi. (A W index of more than 2.07 shows dystopy, while an index of less than 1.87 is normal.)
    • W index = X + Y + alb
    • Where X = [a - {0.21119c + 3.909}]/c and Y = [2a - {0.2497b + 3.909}]/b in mm
    • Distance a is between inner canthi; distance b, between pupils; and distance c, between outer canthi.

Histologic Findings

Histochemical studies in the achromic skin of persons with Waardenburg syndrome show that the melanocytes are absent, or that only a few dihydroxyphenylalanine-positive cells are present.

Ultrastructural observations do not reveal melanocytes, indeterminate dendritic cells, or melanosomes in the keratinocytes of depigmented skin; however, the number of Langerhans cells in the epidermis is normal. The number of melanocytes on the edge of the leukodermas is reduced, and numerous cytoplasmic nuclear abnormalities are noted. Some melanosomes surrounded by a clear halo are found inside of vacuoles. The number of melanocytes in the hypopigmented patches of Waardenburg syndrome is dramatically reduced. These dendritic cells contained poorly melanized melanosomes.

Histopathologic examination of the inner ears of persons with Waardenburg syndrome shows absent organs of Corti, atrophy of the spinal ganglion, and reduced numbers of nerve fibers.

More on Waardenburg Syndrome

Overview: Waardenburg Syndrome
Differential Diagnoses & Workup: Waardenburg Syndrome
Treatment & Medication: Waardenburg Syndrome
Follow-up: Waardenburg Syndrome
Multimedia: Waardenburg Syndrome
References
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References

  1. Waardenburg PJ. A new syndrome combining developmental anomalies of the eyelids, eyebrows and nose root with pigmentary defects of the iris and head hair and with congenital deafness. Am J Hum Genet. Sep 1951;3(3):195-253. [Medline].

  2. Tachibana M. Evidence to suggest that expression of MITF induces melanocyte differentiation and haploinsufficiency of MITF causes Waardenburg syndrome type 2A. Pigment Cell Res. Feb-Apr 1997;10(1-2):25-33. [Medline].

  3. Bondurand N, Pingault V, Goerich DE, et al. Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome. Hum Mol Genet. Aug 12 2000;9(13):1907-17. [Medline].

  4. Chan KK, Wong CK, Lui VC, Tam PK, Sham MH. Analysis of SOX10 mutations identified in Waardenburg-Hirschsprung patients: Differential effects on target gene regulation. J Cell Biochem. Oct 15 2003;90(3):573-85. [Medline].

  5. DeStefano AL, Cupples LA, Arnos KS, et al. Correlation between Waardenburg syndrome phenotype and genotype in a population of individuals with identified PAX3 mutations. Hum Genet. May 1998;102(5):499-506. [Medline].

  6. Dundar M, Lowther G, Colgan J, et al. A case with Waardenburg syndrome presenting with two separate translocations--one reciprocal and one complex. Clin Dysmorphol. Jan 2001;10(1):65-6. [Medline].

  7. Morell R, Carey ML, Lalwani AK, Friedman TB, Asher JH Jr. Three mutations in the paired homeodomain of PAX3 that cause Waardenburg syndrome type 1. Hum Hered. Jan-Feb 1997;47(1):38-41. [Medline].

  8. Sznajer Y, Coldea C, Meire F, Delpierre I, Sekhara T, Touraine RL. A de novo SOX10 mutation causing severe type 4 Waardenburg syndrome without Hirschsprung disease. Am J Med Genet A. Apr 15 2008;146A(8):1038-41. [Medline].

  9. Oysu C, Baserer N, Tinaz M. Audiometric manifestations of Waardenburg's syndrome. Ear Nose Throat J. Sep 2000;79(9):704-9. [Medline].

  10. Tagra S, Talwar AK, Walia RL, Sidhu P. Waardenburg syndrome. Indian J Dermatol Venereol Leprol. Jul-Aug 2006;72(4):326. [Medline].

  11. Shim WK, Derieg M, Powell BR, Hsia YE. Near-total intestinal aganglionosis in the Waardenburg-Shah syndrome. J Pediatr Surg. Dec 1999;34(12):1853-5. [Medline].

  12. Moore SW, Johnson AG. Hirschsprung's disease: genetic and functional associations of Down's and Waardenburg syndromes. Semin Pediatr Surg. Aug 1998;7(3):156-61. [Medline].

  13. Verheij JB, Sival DA, van der Hoeven JH, et al. Shah-Waardenburg syndrome and PCWH associated with SOX10 mutations: a case report and review of the literature. Eur J Paediatr Neurol. Jan 2006;10(1):11-7. [Medline].

  14. Madden C, Halsted MJ, Hopkin RJ, Choo DI, Benton C, Greinwald JH Jr. Temporal bone abnormalities associated with hearing loss in Waardenburg syndrome. Laryngoscope. Nov 2003;113(11):2035-41. [Medline].

  15. Chang T, Hashimoto K, Bawle EV. Spontaneous contraction of leukodermic patches in Waardenburg syndrome. J Dermatol. Nov 1993;20(11):707-11. [Medline].

  16. Dourmishev AL, Dourmishev LA, Schwartz RA, Janniger CK. Waardenburg's syndrome with facial palsy and lingua plicata: is that a new type of disease?. Cutis. Mar 1999;63(3):139-41. [Medline].

  17. Galasso C, Bombardieri R, Cerminara C, Stranci G, Curatolo P. Anophthalmia-Waardenburg syndrome with expanding phenotype: does neural crest play a role?. J Child Neurol. Nov 2007;22(11):1252-5. [Medline].

  18. Milunsky JM, Maher TA, Ito M, Milunsky A. The value of MLPA in Waardenburg syndrome. Genet Test. Summer 2007;11(2):179-82. [Medline].

  19. Dourmishev AL, Dourmishev LA, Schwartz RA, Janniger CK. Waardenburg syndrome. Int J Dermatol. Sep 1999;38(9):656-63. [Medline].

  20. Konno P, Silm H. Waardenburg syndrome. J Eur Acad Dermatol Venereol. Jul 2001;15(4):330-3. [Medline].

  21. Read AP. Waardenburg syndrome. Adv Otorhinolaryngol. 2000;56:32-8. [Medline].

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Further Reading

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Keywords

Waardenburg syndrome, Klein-Waardenburg syndrome, Shah-Waardenburg syndrome, Hirschsprung disease, Hirschsprung's disease, deafness, deafmutism, pigmentary anomalies, white forelock, heterochromia iridis, partial albinism, congenital aganglionic megacolon, dystopia canthorum,

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Contributor Information and Disclosures

Author

Lyubomir A Dourmishev, MD, PhD, Assistant Professor, Department of Dermatology, Medical University, Alexander's University Hospital, Bulgaria
Lyubomir A Dourmishev, MD, PhD is a member of the following medical societies: European Academy of Dermatology and Venereology
Disclosure: Nothing to disclose.

Coauthor(s)

Camila K Janniger, MD, Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, New Jersey Medical School
Camila K Janniger, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Albert C Yan, MD, Section Chief, Associate Professor, Department of Pediatrics, Section of Dermatology, Children's Hospital of Philadelphia and University of Pennsylvania
Albert C Yan, MD is a member of the following medical societies: American Academy of Dermatology, American Academy of Pediatrics, Society for Investigative Dermatology, and Society for Pediatric Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University 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, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital
Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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