Differential Diagnosis
Vineet Relhan, Vijay Kumar Garg, Sneha Ghunawat, Khushbu Mahajan in Comprehensive Textbook on Vitiligo, 2020
Piebaldism is a rare autosomal dominant disorder with an underlying defect of the tyrosine kinase transmembrane receptor on melanocytes, leading to impaired embryonic migration and survival of melanocytes in the skin. It results from a mutation in the c-kit proto-oncogene, mapped to the proximal long arm of chromosome 4 (4q12) or from deletions in the SLUG gene, which is a zinc finger neural crest transcription factor. Recently reported cases of piebaldism, which are milder or more severe than genetically expected, indicate that other factors (e.g., a modifier gene of MC1R) influence skin and hair color [5]. Piebaldism is clinically characterized by congenital extensive, symmetrically distributed depigmentation mainly on the forehead, front of the thorax, and extremities [5]. The extent of the lesions is variable, ranging from only a midfrontal poliosis or white forelock (present in 80%–90% of patients) and minimal areas of depigmentation to depigmentation of almost the entire body and hair (Figure 16.1b). Sometimes in the early age group and in initial stages it is hard to differentiate between piebaldism and segmental vitiligo having leukotrichia. However, a normal area of skin in between depigmented skin is the hallmark sign of piebaldism.
The White Spotting and Steel Hereditary Anemias of the Mouse
Stephen A. Feig, Melvin H. Freedman in Clinical Disorders and Experimental Models of Erythropoietic Failure, 2019
The high mutation rate at the W locus,29 together with the easily discernible and dominant coat color defects associated with mutations at this locus, suggests that mutations within c-kit should exist in other species. Tsujimura and colleagues30 have recently shown that the Ws rat, which exhibits coat color defects, anemia, and mast cell depletion in the homozygous state,31 results from a 12-bp in-frame deletion in the c-kit gene. In humans piebaldism is a rare autosomal dominant disorder characterized by hypopigmentation defects and occasionally karyotypic abnormalities involving chromosome 4. Several groups have shown that at least some patients with piebaldism are heterozygous for either deletions, point mutations, or frameshift mutations within the cytoplasmic kinase domain of the c-kit gene, arguing that this disorder is the human homolog of the dominant W locus in the mouse.32–34 Interestingly, humans with piebaldism do not typically exhibit the erythropoietic abnormalities often apparent in W mutant mice.35
Piebaldism
Electra Nicolaidou, Clio Dessinioti, Andreas D. Katsambas in Hypopigmentation, 2019
Piebaldism is an uncommon autosomal dominant disorder characterized by congenital white skin (leukoderma) and white hair (poliosis) on the frontal scalp, forehead, ventral trunk, and extremities. This condition has been documented throughout history, from the ancient Egyptians to the slave plantations of South America. The term piebald stems from the Latin word for magpie and is used to describe animals whose bodies are covered in black and white patches.1
Outcomes of autologous non-cultured melanocyte keratinocyte transplantation in vitiligo and nevus depigmentosus
Published in Journal of Dermatological Treatment, 2022
Thanyanan Sritanyarat, Chanisada Wongpraparut, Natchaya Jansuwan, Punyanut Yothachai, Nuttaporn Nuntawisuttiwong, Narumol Silpa-archa
MKTP was also shown to be efficacious for the treatment of other leukodermas, such as nevus depigmentosus and piebaldism. For nevus depigmentosus, Mulekar, et al. (9) demonstrated good repigmentation ranging from 80–100% in 3 cases, while 2 other cases had a poor response. However, color mismatch was observed in 2 of the 3 cases that responded to the treatment. van Geel N, et al. (25) reported a single case that had 78% improvement, while Olsson, et al. (26) reported a poor response to treatment in one case. Our study found a good response in three cases of nevus depigmentosus at both the short- and long-term follow-ups.
Novel retinal finding in a patient with 4q12 deletion
Published in Ophthalmic Genetics, 2022
Mario Fruschelli, Nicola Lorusso, Theodora Hadjistilianou, Maria Antonietta Mencarelli, Mirella Bruttini, Alessandra Renieri, Marco Mandalà, Alessandro Di Maggio
Although rare, several ocular findings have been described in patients affected by proximal 4q deletions. Structural ocular anomalies, such as microphthalmia, coloboma and high myopia, have been related to haploinsufficiency for BMP3 and BMP2K genes, codifying a group of pivotal morphogenetic growth factors (1). The deletion reported in our patient however resulted in smaller than previously reported and did not include these genes. Pigmentary changes, such as blue sclerae or pigment retinal clumps, may be related to c-Kit mutations (2,3). Mutations in the c-kit proto-oncogene are responsible for piebaldism, a rare autosomal dominant genodermatosis characterized by the presence of symmetrically distributed, persistent, patches of skin hypo- or depigmentation, caused by congenital absence of melanocytes, usually associated with congenital white forelock (4,5). Piebaldism is part of a wide spectrum of diseases known as auditory-pigmentary disorders (APDs), also including Waardenburg syndrome, oculocutaneous albinism, and Tietz syndrome. All APDs share common clinical features, such as skin and hair pigmentary anomalies, which can be associated with a broad spectrum of ocular, auditory, and neurological disorders. Considering that the association between heterozygous loss-of-function KIT mutations and piebaldism is well established and intellectual disability or developmental delay is frequently observed in individuals with a proximal 4q deletion, skin, and neurological features of our patient can be explained by haploinsufficiency for this genomic region. Although the retinal findings herein reported have never been described before in patients affected by 4q12 deletion, we do not exclude that they could represent a manifestation of the peculiar genetic asset of the patient, related to dysfunction in pigment epithelium/neuroretinal metabolic activity.
Related Knowledge Centers
- Mendelian Inheritance
- Melanocyte
- Skin Condition
- Waardenburg Syndrome
- Hirschsprung'S Disease
- Vitiligo
- Poliosis
- Albinism
- Neurocristopathy
- Kit