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Association of lentiginous mosaicism and congenital cataract in a girl

European Journal of Dermatology. Volume 16, Number 4, 360-2, July-August 2006, Genes and skin

Summary

Author(s) : Sandra P Toelle, Eugen Boltshauser, M Gabriela Wirth, Peter Itin , University Children’s Hospital, Department of Neurology, Steinwiesstrasse 75, 8032 Zurich, SwitzerlandFax: (+41) 44 2667163, University Hospital, Department of Ophthalmology, Zurich, Switzerland, Cantonal Hospital, Department of Dermatology, Aarau, Switzerland.

Summary : Partial unilateral lentiginosis (PUL) is a rare pigmentary disorder characterized by multiple lentigines on otherwise normal skin affecting one side of the body. We report on a girl with an extensive form of bilateral lentiginosis with systematized segmental distribution and a unilateral congenital cataract. The arrangement of the lentigines is reminiscent of a checkerboard pattern. The benign condition is discussed in the context of systemic diseases with lentigines.

Keywords : cataract, lentiginosis, mosaicism

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ARTICLE

Auteur(s) : Sandra P Toelle¹, Eugen Boltshauser¹, M Gabriela Wirth², Peter Itin³

¹University Children’s Hospital, Department of Neurology, Steinwiesstrasse 75, 8032 Zurich, SwitzerlandFax: (+41) 44 2667163
²University Hospital, Department of Ophthalmology, Zurich, Switzerland
³Cantonal Hospital, Department of Dermatology, Aarau, Switzerland

accepté le 12 Avril 2006

Partial unilateral lentiginosis (PUL) is characterized by small, discrete pigmented macules, which develop on normal appearing skin, arranged in clusters in a checker-board pattern, usually unilaterally over limited areas of the body. It is a rare disorder of cutaneous pigmentation, first described by McKelway [1] in 1904 in a patient with unilateral distribution. Since then, papers on several patients have been published with different descriptive terms such as segmental lentiginosis, lentiginous mosaicism, zosteriform lentiginous nevus or agminated lentiginosis used synonymously. Although most cases reported had no associated disorder, some of them showed neurological, endocrinological or hematological abnormalities.We report on a girl with a unilateral congenital cataract and an extensive form of bilateral lentiginosis, a combination not published so far. Because of the peculiar and bilateral distribution of the lentigines the term lentiginous mosaicism (LM) rather than PUL was considered more appropriate and used in this report.

Case report

This 10-year-old girl was born after an uneventful pregnancy. She has two healthy younger brothers and the family history is non-contributory apart from three relatives (grandmother, great-aunt and great-grandmother) with carcinoma. A minor anterior polar cataract in her left eye was noticed during the first days of life. Mild amblyopia therapy was successfully administered between the ages of two and four. As a baby an area of hyperpigmentation on her left hand was noted by the parents. Over the years multiple areas of sharply limited, brownish macules were noted. At the age of four years a sonography of the abdomen, MRI of the brain and radiographs of the skeleton were performed in another hospital, all with normal results. The diagnosis of possible neurofibromatosis type 1 was made.

The girl presented to our institution at the age of 10 years because of progressive skin manifestations and the question of neurofibromatosis type 1. Her weight, length and head circumference were within the normal percentiles. General and neurological examination was completely normal with the exception of a small anterior polar cataract in her left eye. Lisch nodules were not present. She is an excellent scholar and dances in a ballet ensemble. Skin (figures 1-3): multiple sharply demarcated and irregularly shaped areas with clustering of pigmented macules on a normal-appearing skin. The distribution of the lentigines is over the left frontal region, left cheek, left pectoral and shoulder region with sharp demarcation at the midline, the right shoulder, arm and abdomen, the lumbar region bilaterally and the left inguinal region. The arrangement is segmental and reminiscent of a checkerboard pattern on the trunk and flag-like on the arm. Within these areas a few café-au-lait spots of 1 cm diameter or less were observed. There were no axillary freckles and no cutaneous neurofibromas. The parents reliably reported that the number of macules and the extent of the areas had gradually increased and that even new areas with lentigines had appeared over the years.

Discussion

There are some syndromes combining multiple lesions of simple lentigo with other conditions; these are (with corresponding MIM numbers) summarized in table 1( Table 1 ). In patients with multiple widespread lentigines a thorough physical evaluation with particular emphasis on the cardiovascular system is mandatory. The distribution of the lentigines in the LEOPARD, NAME, LAMB or Carney syndromes is typically not segmental but disseminated, in patients with Peutz-Jeghers syndrome limited to the lips, buccal mucosa and digits, and in patients with centrofacial lentiginosis limited to the face, therefore clearly differing from our patient with the peculiar distribution pattern and sharp demarcation of the patchy areas of lentigines. The familial lentiginosis syndromes were reviewed by Bauer and Strarakis recently [2].

PUL typically has unilateral distribution of the lentigines. Bilateral cases are extremely rare: a mosaic-like distribution similar to our patient was reported by Davis and Shaw [3] in a woman. Micali [4] described a woman with bilateral involvement of the neck, chin and cheeks, and parts of the left trunk. Parslew and Verbov [5] described a girl with PUL affecting the left side of the neck, left shoulder, left upper arm and right side of the face. Both women and the girl were otherwise healthy.

PUL has been associated with different cutaneous and systemic abnormalities, although several of them might be coincidental. Patients with PUL and ipsilateral [6, 7], contralateral [8], as well as bilateral [9] segmental neurofibromatosis have been reported. Several authors have supported the hypothesis that PUL is a part of segmental neurofibromatosis [10], representing a mosaic manifestation [7] or a forme fruste [11] of neurofibromatosis type 1. Postzygotic somatic mutations could be an explanation for the presence of both segmental neurofibromatosis and PUL in the same patient [6, 8, 9].

The pathogenesis of PUL has been hypothesized as involving somatic mosaicism [3]. The distribution of lentigines in the checker-board pattern in our patient supports the idea of postzygotic mutation in patients with PUL. Ocular involvement was reported by Schaffer et al. [12]. This patient had an area of brown pigmentation on the bulbar conjunctiva. A congenital cataract as in our patient or any other ocular involvement in a patient with LM has never been reported so far. Anterior polar cataract usually occurs unilaterally and sporadically, and seldom as an autosomal dominant disease, which was not the case in our patient.

PUL should be distinguished from speckled lentiginous nevus (nevus spilus) as it occurs on normal skin and not within an area of macular hyperpigmentation [13, 14]. Speckled lentiginous nevus syndrome has been recognized as a neurocutaneous phenotype characterized by a speckled lentiginous nevus and ipsilateral neurological abnormalities such as hyperhidrosis, muscular weakness and dysesthesia [15].

After the initial appearance of pigmented macules during childhood, patients with PUL usually have a gradual extension of lesions over months to years. This is in contrast to the background hyperpigmentation of a speckled lentiginous nevus, in which the shape remains stable and the size increases only in proportion to the growth of the individual [5].
Table 1 Syndromes with lentigines

LEOPARD syndrome MIM #151100	acronym for: multiple lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness.
Carney complex MIM #160980	multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumors, and psammomatous melanotic schwannomas
including • NAME syndrome • LAMB syndrome	acronym for: nevi, atrial myxoma, mucinosis of the skin and endocrine overactivity
	acronym for: lentigines, atrial myxoma, mucocutaneous myxomas and blue nevi
Peutz-Jeghers syndrome MIM #175200	melanocytic macules of the lips, buccal mucosa, and digits; multiple gastrointestinal hamartomatous polyposis, increased risk of various neoplasms
Centrofacial lentiginosis	lentigines in the face and mental retardation

Conclusion

LM with bilateral involvement is a rare benign disorder and not related to any other disabling genetic disorders associated with lentiginosis. The distribution of the lentigines makes it possible to rule out clinically the syndromes with multiple widespread lentigines. The extensive bilateral segmental distribution in our patient in combination with the absence of any other clinical signs of neurofibromatosis type 1, especially the absence of Lisch nodules and axillary frecklings although the patient shows unilateral lentiginosis on the left front and both deltoids is an important argument against segmental neurofibromatosis type 1. One author (EB) has seen 12 patients with segmental neurofibromatosis type 1 (i.e. multiple café-au-lait spots and freckling confined to a body part, some with Lisch nodules), two males were fathers of children with generalized neurofibromatosis type 1 [16]. In all cases the skin changes were seen since early childhood, they were unilateral, the maximal area covered was one (upper) body quadrant and freckling was not the predominant manifestation. This is in contrast to our girl with impressive, extensive and bilateral lentiginosis.

The exclusion of neurofibromatosis type 1 is very important, both for the avoidance of unnecessary investigations and for the psychological and genetic consequences to the patient himself. The extent of LM seems to be progressive during childhood; the long term prognosis is unknown, but neither malignant transformation nor familial occurrence has been reported.

References

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