Wednesday, 25 February 2015

Waardenburg syndrome

Piebaldism (Latin and Middle English magpie and Middle English bald, early meaning of white) is a rare, usually autosomal-dominant syndrome with variable phenotype, presenting at birth. Patches of skin totally devoid of pigment are present at birth and usually remain unchanged throughout life. A white forelock can be the only manifestation of the disease. The depigmented lesions may repigment spontaneously, or especially after injury. Regression of the white forelock has also been reported. Photoprotective preparations should be prescribed to protect the amelanotic areas from burning with sun exposure. Other measures include e.g. cosmetic camouflage and grafts of autologous cultured melanocytes.

Waardenburg syndrome (WS) was first described by a Dutch ophthalmologist in 1951. Patients with WS often have characteristic brilliant blue irides as shown in this patient or different coloured irides, such as one blue iris and one brown iris. Sometimes one iris has segments of two different colours. It is one of the syndromes in which extracutaneous manifestations accompany the piebaldism. The symptom most likely to be of practical importance is deafness. Typically piebaldism is not associated with deafness, although piebaldism associated deafness is referred to as Woolf syndrome

There are four classical clinical variants of WS as shown in the table but recent molecular genetics findings have demonstrated at least nine distinct genetic subtypes of WS syndrome, several of which correspond to distinct clinical subtypes not included in these four classical subtypes. WS affects an estimated 1 in 40,000 people. It accounts for 2 to 5 percent of all cases of congenital hearing loss. Types I and II are the most common forms of WS.

WS is usually inherited in an autosomal dominant pattern but sometimes has an autosomal recessive pattern of inheritance as in this patient - figure 1 (her cousin is affected too but with congenital deafness in addition - figure 2).

Although most patients with WS have normal hearing, moderate to profound hearing loss can occur in one or both ears. Hearing loss occurs more often in people with type II than in those with type I but this higher incidence may be due to the difficulty of diagnosing WS2 in patients without hearing loss. Sensorineural deafness results from failure of melanoblasts to migrate to or survive in the stria vascularis in the lateral wall of the cochlea. As shown in the table, mutations in the SOX10EDN3, or EDNRB genes cause type IV Waardenburg syndrome. In addition to melanocyte development, these genes are important for the development of nerve cells in the large intestine. Mutations in any of these genes result in hearing loss, changes in pigmentation, and intestinal problems related to Hirschsprung disease. In Tietz syndrome there are sensorineural deafness, eyebrow hypoplasia, generalized hypopigmentation rather than the localized pigment loss of WS.

All WS forms show marked variability, even within families, and at present it is not possible to predict the severity, even when a mutation is detected. Variable expression and penetrance explain milder or incomplete phenotypes.

Cochlear implantation should be considered a rehabilitative option for WS children with profound deafness, enabling the development and improvement of speech perception and production abilities. 

Figure 1
Note the blue irides and piebaldism (left hand). Poliosis (white forelock) is not shown in the photo (but the patient has it). Poliosis itself is defined as congenital (as in this syndrome) or acquired presence of a localized patch of white hair resulting from the absence or deficiency of melanin in a group of neighbouring follicles. The white forelock can be absent. Premature greying may develop with or without the white forelock.

Figure 2

MITF = microphthalmia associated transcription factor. MITF controls the expression of various genes that are essential for normal melanin synthesis in melanocytes.

This page was last updated in March 2015

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Main Works of Reference List (The first eight are my top favourites)

  • British National Formulary
  • British National Formulary for Children
  • Guidelines (BAD - BASHH - BHIVA - Uroweb)
  • Oxford Handbook of Genitourinary Medicine, HIV, and Sexual Health
  • Oxford Handbook of Medical Dermatology
  • Rook's Textbook of Dermatology
  • Simple Skin Surgery
  • Weedon's Skin Pathology
  • A Concise Atlas of Dermatopathology (P Mckee)
  • Andrews' Diseases of the Skin
  • Andrology (Nieschlag E FRCP, Behre M and Nieschlag S)
  • Bailey and Love's Short Practice of Surgery
  • Davidson's Essentials of Medicine
  • Davidson's Principles and Practice of Medicine
  • Fitzpatrick's Colour Atlas and Synopsis of Clinical Dermatology (Klaus Wolff FRCP and Richard Allen Johnson)
  • Fitzpatrick’s Dermatology in General Medicine
  • Ganong's Review of Medical Physiology
  • Gray's Anatomy
  • Hamilton Bailey's Demonstrations of Physical Signs in Clinical Surgery
  • Hutchison's Clinical Methods
  • Lever's Histopathology of the Skin
  • Lever's Histopathology of the Skin (Atlas and Synopsis)
  • Macleod's Clinical Examination
  • Martindale: The Complete Drug Reference
  • Oxford Handbook of Clinical Examination and Practical Skills
  • Oxford Textbook of Medicine
  • Practical Dermatopathology (R Rapini)
  • Sexually Transmitted Diseases (Holmes K et al)
  • Statistics in Clinical Practice (D Coggon FRCP)
  • Stockley's Drug Interactions
  • Treatment of Skin Disease: Comprehensive Therapeutic Strategies
  • Yen & Jaffe's Reproductive Endocrinology