Dear Editor

Developmental mosaicism in the eye may follow the “lines of Blaschko” Ruggieri M et al. nicely described the ophthalmological manifestations in segmental neurofibromatosis type 1 [1]. They postulated that segmental NF1 is a somatic mosaicism for the NF1-gene expressing two different embryological tissues in the eye.

Previously we described a patient with unilateral sectorial hyperpigmented skin lesions on his left shoulder and additional grouped CHRPE in the left eye. These sectorial pigmentations were also noticed during the first months of life and did not correspond to the distribution of cutaneous nerves (dermatomes) [2]. Pigmentary mosaicism of the human skin follow well-established segmental archetypes and were published by the dermatologist Alfred Blaschko in 1901. He emphasized that these “nevus lines” could neither be related to the distribution of the nerves nor to vascular or lymphatic structures of the skin [3]. These “lines of Blaschko” therefore reflect the dorso- ventral outgrowth of precursor of the skin and may manifest the stream, distribution, migration and proliferation of embryonic tissue. They possibly originate during early embryogenesis by various genetic mechanisms including postzygotic mutations, functional X-chromosomal mosaicism, gametic halfchromatid mutations or loss of a heterozygosity (LOH). If one of these events occurs, both homozygosity or heterozygosity may predispose to sectorial pigmentation of these somatic cells. The distinct stem-cell clones may give rise to the observed sectorial mosaicism [4-5].

The precise pattern of the cutaneous lines of Blaschko on the face, neck and trunk of the body were reported by Happle et al. after observing numerous clinical examples of segmental skin disorders [6]. Analogous patterns for the “lines of Blaschko” in the eye [7] were described for heterozygous women with one randomly inactivated X-chromosome (Lyonization) for X-linked Lowe-Syndrome exhibiting segmental cataracts [8] or X-linked ocular albinism with stria- like patchy fundus hypopigmentations with orientation toward the optic nerve [9]. Recently we reviewed the literature over a period of 130 years and identidied 41 publications with grouped congenital hypertrophy of the retinal pigment epithelium (CHRPE). The sectorial pigmentations radiated in a crescent shape from the optic nerve towards the periphery, providing evidence, that there was no causal relationship to the retinal nerve fiber system. We suggested that these lesions may follow developmental lines in the eye analogous to the cutaneous lines of Blaschko. The sectorial pattern of the neuroepithelial pigment epithelial in grouped CHRPE may therefore reflect the outgrowth and migration of RPE-cells during embryogenesis [10].

The important findings by Ruggieri M et al. give further evidence, that two different embryological cellular clones may present sectorial mosaicism in the eye following the lines of Blaschko.

References

(1) Ruggieri M, Pavone P, Polizzi A, Di Pietro M, Scuderi A, Gabriele A, Spalice A, Iannetti P. Ophthalmological manifestations in segmental neurofibromatosis type 1. Br J Ophthalmol 2004;88:1429-1433

(2) Meyer CH, Freyschmidt-Paul P, Happle R, Kroll P. Unilateral linear hyperpigmentation of the skin with ipsilateral sectorial hyperpigmentation of the retina. Am J Med Gen 2004;126A:89-92.

(3) Blaschko A. Die Nervenverteilung in der Haut in ihrer Beziehung zu den Erkrankungen der Haut. 1901; Wien-Leipzig, W. Braumüller

(4) Happle R. Transposable elements and the lines of Blaschko: A new perspective. Dermatology 2002;204;4-7.

(5) Happle R. Loss of heterozygosity in human skin. J Am Acad Dermantol 1999;41:143-61.

(6) Happle R, Assim A. The lines of Blaschko on the head and neck. J Am Acad Dermatol 2001;44:612-5.

(7) Rott HD. Extracutaneous analogies of Blaschko lines. Am J Med Gen 1999;85:338-341.

(8) Happle R, Küchle HJ. Sectorial cataract: a possible explanation Lyonisation. Lancet 1983;2:919-20.

(9) Rott HD, Rix R. Fundus changes in a carrier women for X-linked ocular albinism: a proof of Lyon’s hypothesis in man. Klin Monatsbl Augenheilkd 1984;184:128-9.

(10) Meyer CH, Rodrigues EB, Mennel S, Schmidt JC, Kroll P. Grouped congenital hypertrophy of the retinal pigment epithelium follows developmental patterns of pigmentary mosaicism. Ophthalmology (accepted)