#172800
ICD+
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| PIEBALD TRAIT; PBT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| PIEBALDISM | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Phenotype Gene Relationships | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinical Synopsis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| A number sign (#) is used with this entry because of evidence that piebaldism can be caused by mutation in the KIT protooncogene (164920). The previous mapping of the KIT locus to 4q11-q12 is consistent with the location of piebald trait to 4q12 on the basis of chromosomal aberrations and homology with the mouse. Some cases of piebaldism are caused by mutation in the gene encoding the zinc finger transcription factor SNAI2 (602150), located on chromosome 8q11. The features of piebaldism are white forelock and absence of pigmentation of the medial portion of the forehead, eyebrows, and chin and of the ventral chest, abdomen, and extremities. The borders of unpigmented areas are hyperpigmented. Heterochromia iridis occurs in some. Keeler (1934) described a Louisiana black family in which the disorder could be traced back to a woman born in 1853. Sundfor (1939) described a family in which many persons had a white forelock, often with unpigmented patches on the forehead, limbs, body, etc. Comings and Odland (1966) found the trait in 6 generations. A genetic defect in melanoblast differentiation was postulated. Loewenthal (1959) assigned the name albinoidism to a dominantly inherited condition characterized by a white 'blaze' in the scalp hair, usually the forelock, and/or patches of leukoderma. Epitheliomas occurred with increased frequency. The designation albinoidism is better reserved for the recessive condition simulating true albinism. The statement that deafness does not occur in persons with the piebald trait as a pleiotropic effect of the gene may not be true. Reed et al. (1967) noted profound deafness with piebaldism in 2 patients. Some of the patients of Comings and Odland (1966) were deaf. Selmanowitz et al. (1977) published a pedigree with at least 10 affected persons in 4 generations. Winship et al. (1991) described 7 affected persons in 3 generations. Two other affected individuals were deceased. The disorder seemed distinct from Waardenburg syndrome (193500). White forelock and patches of leukoderma occur also in Waardenburg syndrome and in Fanconi anemia (227650). Farag et al. (1992) described a Bedouin kindred with 19 affected persons in 5 generations. In mice, aganglionic megacolon is associated with the piebald trait (Bielschowsky and Schofield, 1962), inherited probably as an autosomal recessive. Dennis (1978) observed a black newborn with Hirschsprung disease (142623) (diagnosed by rectal biopsy), white forelock, V-shaped extension of the anterior fontanel into the metopic suture, and canthal distances of 2.5 cm (inner) and 6 cm (outer). From India, Mahakrishnan and Srinivasan (1980) reported Hirschsprung disease in 2 brothers who had piebaldness (white forelock, patches of depigmentation over the upper third of the forearms and the lower part of the arms, diffuse hypopigmentation of the abdomen and chest, and heterochromia iridis); their father had a white forelock also. The piebald character, which is widely distributed in the animal kingdom, is an intriguing problem in developmental genetics. Does the skin have pigmented and unpigmented clones of melanocytes? Is there a deficient number of melanocytes in unpigmented areas? Is there a patchy peculiarity of tissues that is inimical to normal melanocyte development or function? There are probably other possibilities. As in spotting mutations in all species, the details of the gene-determined abnormality in development is not clear. Presumably it is a peculiarity of neural crest migration. Funderburk and Crandall (1974) reported a 3-year-old boy with moderate mental retardation, short stature, and integumentary pigment changes typical of the autosomal dominant piebald syndrome. The patient's chromosomes showed a reciprocal translocation and an intercalary deletion of one chromosome 4. Lacassie et al. (1977) found a similar case that illustrated the association of piebald trait with interstitial deletion of the long arm of chromosome 4 (4q13). The deleted segment was adjacent to centromeric heterochromatin, raising the question of position effect. Hoo et al. (1986) described a case of de novo deletion in 4q and pointed out that several of the patients with comparable deletions have had abnormal skin pigmentation compatible with the piebald trait. Further analysis suggested that the piebald trait locus may be situated in band 4q12. Yamamoto et al. (1989) reported piebald trait in a child with de novo interstitial deletion of 4q, specifically 4q12-q21.1. Other features included mental and motor retardation despite normal somatic growth, aplasia cutis of the scalp, flat nasal root and tip, micrognathia, widely spaced nipples, and agenesis of the right kidney. Hulten et al. (1987) reported a presumed homozygote; the severely affected child was born to heterozygous parents. He had complete absence of hair and pigmentation and had blue irides. Lyon (1988) pointed out that the location of the W locus on mouse chromosome 5 supports the location of a piebald trait gene on chromosome 4 of man since there is a large, conserved synteny group on those chromosomes of the 2 species. Geissler et al. (1988) identified cloned DNA markers near the W locus and determined the genetic distance from a number of other loci. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Molecular Genetics | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Giebel and Spritz (1991) identified a mutation in the KIT protooncogene as the cause of piebaldism; see 164920.0001. Spritz and Beighton (1998) described a South African girl of Xhosa stock with severe piebaldism and profound congenital sensorineural deafness. In this patient they identified a novel missense substitution, arg796 to gly, at a highly conserved residue in the intracellular kinase domain of the KIT protooncogene (164920.0016). In 3 of 17 unrelated patients with piebaldism who had no mutations in the KIT protooncogene, Sanchez-Martin et al. (2003) identified a heterozygous deletion of the SNAI2 gene (602150.0002). Two of the patients were sporadic cases and the other had 2 affected sibs and an affected daughter; all parents were nonconsanguineous and unaffected. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| History | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| George Catlin (1796-1872), painter of the American Indians, painted an affected Mandan Indian. Multiple members of the group were said to have been affected. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| See Also: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Comings and Odland (1965); Cooke (1952); Cromwell (1940); Fitch (1937); Froggatt (1951); Jahr and McIntyre (1954) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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