Piebaldism E70.35

Congenital, autosomal-dominantly inherited, circumscribed white spotting of the skin, caused by (mostly) complete absence of melanocytes in lesional skin. Mutations in the KIT (see kit below) and SLUG (SNAI2 - Snail homologue 2 transcription factor) genes have been detected (Saleem MD et al. 2019).

The "classical" Piebaldism is a pure skin anomaly.

Poliosis as a congenital or acquired, heart-shaped white discoloration of the hair (white curl of hair in the forehead area) can occur as a partial symptom of various other syndromes (see below).

Prevalence: 3-5/100,000 inhabitants/year.

In most cases, inactivating mutations are present in the c-Kit receptor gene, which is located on chromosome 4q12.

The c-Kit receptor is responsible for the migration of melanoblasts from the neural crest, for their survival as well as for their proliferation.

Furthermore, deletions in the SNAI2 gene encoding a transcription factor have been described.

Mostly coin-sized, sharply defined, amelanotic, isolated, symmetrical or systematized spots, white forelock. More rarely also café-au-lait stains.

Six field complex: Poliosis circumscripta and pigment deficiency in the chin, neck, middle of the trunk and distal extremities.

Partial symptoms of the following syndromes:

• Klein-Waardenburg Syndrome
• Tietz Syndrome
• Chédiak Higashi Syndrome
• optional for Stargardt's Syndrome.

In the lesional areas the melanin is missing. Melanocytes are missing completely.

Clinical:

Vitiligo: Rarely isolated focus. Not congenital but acquired.

Albinism: Congenital disorder of melanin synthesis with normal intraepidermal melanocyte count (!). Never localized but generalized hypomelanosis of skin, hair and eyes (oculocutaneous albinism) or only of the eyes (ocular albinism).

Nevus depigmentosus. So far, an actually existing difference of both anomalies has not been clarified. Systematized"(cutaneous mosaics) depigmentations have been described for both syndromes.

In nevus depigmentosus, melanocytes are typically detectable in the epidermis. There is a disturbance of melanosome transfer.

Nevus anaemicus: Evidence is provided by the friction test, which is negative in nevus anaemicus.

The c-kit receptor is a protein of the tyrosine kinase family of transmembrane receptors. c-Kit is expressed on the surface of melanocytes and acts as a receptor for growth factors. A reduction or even the absence of c-Kit-dependent signal transduction then leads to a reduced proliferation and migration of embryonic melanoblasts from the neural crest. This usually results in a complete absence or a significant reduction of melanocytes in the corresponding skin areas. A clinical picture analogous to the piebaldism of humans is frequently observed in horses (pinto) and cows (black and white cows) and is called leucism. The gene mutation described above can also be detected in these mammals.

3 year old boy who had a stripe-like white spot since birth and later developed a white curl(poliosis) in this area. Since early infancy the mother observed further whitish spots on the belly and later on the left arm and right knee. In the last few weeks, after repeated exposure to the sun, single pigmented spots appeared within the depigmented area on the abdomen. The boy was mentally completely normal and showed no other physical retardations. Medium exposure to sunlight leads to premature dermatitis solaris in the lesional areas.

1. Böhm M (2015) Differential diagnosis of hypomelanosis. dermatologist 66: 945-958
2. Fistarol SK et al (2010) Pigment disorders. SDDG 8:187-203
3. Garg T et al (2003) Autologous punch grafting for repigmentation in piebaldism. J Dermatol 30: 849-7850
4. Olsson MJ et al (2002) Long-term follow-up of leucoderma patients treated with transplants of autologous cultured melanocytes, ultrathin epidermal sheets and basal cell layer suspension. Br J Dermatol 147: 893-904
5. Saleem MD et al (2019) Biology of human melanocyte development, Piebaldism, and Waardenburg syndrome. Pediatric Dermatol 36:72-84.
6. Sleiman R et al (2013) Poliosis circumscripta: overview andunderlying
   causes. J Am Acad Dermatol 69:625-633