Piebaldism
True human piebaldism is a rare disorder. Piebaldism involves
distinct patches of skin and hair that contain no pigment. Melanocytes
are completely lacking in these hypopigmented regions. Surrounding
skin and hair show normal pigmentation. Piebaldism often presents
as a white forelock of scalp hair, but patches of depigmented hair
or skin can occur anywhere on the body and there may be more than
one affected area. Piebaldism can look much like poliosis in its
basic presentation. The difference is that piebaldism is a genetic
abnormality that affects a single, specific gene.
In contrast to autosomal recessive albinism, classic piebaldism
is a genetic disease with autosomal dominant inheritance. It involves
mutations of a gene called the kit proto-oncogene that encode a
melanocyte pigment cell surface receptor called tyrosine kinase,
The ligand that binds to this cell receptor is an embryonic stem
cell growth factor. This growth factor has been given various names
in the medical literature including; steel factor (SLF), stem cell
factor, mast cell growth factor, and Kit ligand. There are several
subtly different genetic abnormalities that can occur in the kit
proto-oncogene but regardless of the particular mutation involved
the result is that the tyrosine kinase cell receptor does not function
properly.
When the defective tyrosine kinase receptor is bound by the embryonic
growth factor, it does not correctly transfer a signal to nucleus
of the cell on which it is expressed. Without this signal from the
receptor, the cell nucleus does not know that it should start to
transcribe particular genes in order to make cell proteins involved
in proliferation and differentiation of melanocytes. This results
in reduced melanocyte cell proliferation or reduces cell migration
during embryologic development. The result is that the affected
individual is born with patches of skin in which no melanocyte cells
are present. Melanocye cells are the cells that produce pigment
for skin and hair, so their absence in an area of skin means that
the skin and hair there is not pigmented.
Although piebaldism usually involves symptoms strictly limited
to changes in hair and skin color, there is a suggestion that the
condition can also involve deafness for some people. Several case
reports have identified varying degrees of deafness in association
with a white forelock and/or patches of leukoderma (Reed 1967, Comings
1966, Selmanowitz 1977).
Treatments are mostly experimental in nature. For small white spots
the most simple answer is to cut out the affected skin. However,
with larger areas of affected skin and hair this is not practical.
Some experiments have been conducted in which melanocyte pigment
cells are taken from normally pigmented skin and transplanted to
the unpigmented skin. This approach can be quite successful although
results from patient to patient are variable.
Piebaldism
references
- 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.
- Horikawa
T, Mishima Y, Nishino K, Ichihashi M. Horizontal and vertical
pigment spread into surrounding piebald epidermis and hair follicles
after suction blister epidermal grafting. Pigment Cell Res. 1999
Jun;12(3):175-80.
- Kumagai
N, Uchikoshi T. Treatment of extensive hypomelanosis with autologous
cultured epithelium. Ann Plast Surg. 1997 Jul;39(1):68-73.
- Ezoe K,
Holmes SA, Ho L, Bennett CP, Bolognia JL, Brueton L, Burn J, Falabella
R, Gatto EM, Ishii N, 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.
- Fleischman
RA. Protein Human piebald trait resulting from a dominant negative
mutant allele of the c-kit membrane receptor gene. J Clin Invest.
1992 Jun;89(6):1713-7.
- Spritz
RA, Giebel LB, Holmes SA. Dominant negative and loss of function
mutations of the c-kit (mast/stem cell growth factor receptor)
proto-oncogene in human piebaldism. Am J Hum Genet. 1992 Feb;50(2):261-9.
- Ward KA, Moss C, Sanders DS. Human piebaldism:
relationship between phenotype and site of kit gene mutation.
Br J Dermatol. 1995 Jun;132(6):929-35.
- Spritz RA. Molecular basis of human piebaldism.
J Invest Dermatol. 1994 Nov;103(5 Suppl):137S-140S.
- Spritz RA, Ho L, Strunk KM. Inhibition
of proliferation of human melanocytes by a KIT antisense oligodeoxynucleotide:
implications for human piebaldism and mouse dominant white spotting
(W). J Invest Dermatol. 1994 Aug;103(2):148-50.
- Pavan WJ, Tilghman SM. Piebald lethal (sl)
acts early to disrupt the development of neural crest-derived
melanocytes. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7159-63.
- Fleischman RA, Saltman DL, Stastny V, Zneimer
S. Deletion of the c-kit protooncogene in the human developmental
defect piebald trait. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10885-9.
- Winship I, Young K, Martell R, Ramesar R, Curtis
D, Beighton P. Piebaldism: an autonomous autosomal dominant entity.
Clin Genet. 1991 May;39(5):330-7.
- Giebel LB, Spritz RA. Protein Mutation
of the KIT (mast/stem cell growth factor receptor) protooncogene
in human piebaldism. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8696-9.
- Kuster W. [Piebaldism]. Hautarzt. 1987
Aug;38(8):481-3.
- Selmanowitz VJ, Rabinowitz AD, Orentreich
N, Wenk E. Pigmentary correction of piebaldism by autografts.
I. Procedures and clinical findings. J Dermatol Surg Oncol. 1977
Nov-Dec;3(6):615-22.
- Reed WB, Stone VM, Boder E, Ziprkowski
L. Pigmentary disorders in association with congenital deafness.
Arch Dermatol. 1967 Feb;95(2):176-86.
- Comings DE, Odland GF. Partial albinism.
JAMA. 1966 Feb 14;195(7):519-23.
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