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 SOX10, EDN3, 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.
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 SOX10, EDN3, 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.
