Case Reports and Small Case Series
December 1999

Retinal Pigment Mosaicism in Pallister-Killian Syndrome (Mosaic Tetrasomy 12p)

Author Affiliations

Copyright 1999 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.1999

Arch Ophthalmol. 1999;117(12):1648-1649. doi:

Pallister-Killian syndrome (PKS) was first reported by Pallister in 19771 and later by Teschler-Nicola and Killian in 1981.2 This condition is caused by a mosaic tetrasomy of chromosome 12p, which is detectable in cultured fibroblastoid cells but generally not in peripheral lymphocytes. Systemic features in childhood are numerous and variable, and include most frequently "coarse" facial features, midface malformations, psychomotor delay, hypotonia, scalp hair sparsity, and variegated lightly and darkly pigmented skin.19 We describe a patient with the novel ocular manifestation of retinal pigmentary mosaicism, and confirm for the first time that the fibroblast cell line from the darkly pigmented skin contains the chromosomal tetrasomy.

Report of a Case

A 4½-month-old Hispanic boy was referred for evaluation of an irregular pupil. He was born at 35 weeks to nonconsanguineous parents; the pregnancy was complicated by maternal amphetamine use. The child was noted at birth to have bilateral inguinal hernias and dislocated hips, a cleft palate, a patent ductus arteriosus, and dysmorphic features. Whorled and streaky dark and light pigmentation was present on the skin of the trunk (Figure 1).

Figure 1.
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External color photograph of the patient's back taken at age 4½ months showing stripes of whorled and streaky light and dark pigmentation.

On examination, reasonable visual following (or fixation) behavior for age was demonstrated. There was hypertelorism and a low hairline. The right iris had an inferonasal coloboma; the anterior segments were otherwise normal. The fundus examination showed asymmetric patches and streaks of darkly and lightly pigmented retina (Figure 2), radiating outward from the optic discs in a petalloid fashion. There was concern about right optic nerve hypoplasia; the left optic nerve looked normal. The cycloplegic refraction was −6.25+1.00 × 90 OD and +4.25S OS. A subsequent visit showed a 40–prism diopter right esotropia.

Figure 2.
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Posterior (left) and peripheral (right) color fundus photographs (28-diopter lens) taken at age 2 years showing streaks and patches of alternating dark and light retinal pigmentation. The demarcation between regions is sharp.

The child was lost to ophthalmologic follow-up until age 2 years, by which time a diagnosis of PKS had been suggested although not confirmed by cytogenetic testing. An examination under anesthesia was performed, and punch biopsies of both lightly and darkly pigmented skin were obtained. Chromosome studies performed on fibroblasts cultured from the darkly pigmented skin revealed a mos 47,XY,+i(12)(q10)/46,XY karyotype in 27 of 41 metaphase spreads; 14 of 41 metaphase spreads showed a 46,XY karyotype. Fibroblasts cultured from the lightly pigmented skin biopsy specimen revealed a normal 46,XY karyotype in all 50 metaphase spreads. The karyotype derived from the dark (hyperpigmented) skin is consistent with PKS.


To our knowledge, we are the first to describe retinal pigment mosaicism in PKS. This finding is similar to the characteristic variegated skin color. If we assume that the retinal pigment mosaicism is caused by karyotype mosaicism, this suggests that the short arm of chromosome 12 contains a gene that affects retinal pigment epithelium (RPE) pigment production. We cannot explain why this striking fundus feature was not noted in previous case reports, except to postulate that the level of mosaicism in the RPE was sufficiently low (whether the karyotype was predominantly normal or abnormal) that sharp demarcations between affected and unaffected RPE could not be seen.

An extensive review of the literature revealed only one other diagnosis with similar cutaneous and fundus findings: hypomelanosis of Ito. This rare neurocutaneous disorder consists of skin pigmentary mosaicism, patchy retinal hypopigmentation, and seizures. Other ocular abnormalities overlap with those of PKS (Table 1), and include strabismus, hypertelorism, epicanthal folds, scleralization of the cornea, iris heterochromia, and microphthalmia. The karyotype in hypomelanosis of Ito is normal.

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Reported Ocular Manifestations of Pallister-Killian Syndrome

Our case suggests that infants with dysmorphic facial features, other congenital abnormalities, and variegated skin pigmentation would benefit from a fundus examination. The presence of patchy variability in RPE pigmentation may be consistent with PKS. In this case, standard karyotyping of peripheral blood lymphocytes is inadequate to rule out the diagnosis. Fibroblasts cultured from a biopsy of the abnormally hyperpigmented skin would reveal the mosaic tetrasomy 12p.

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Article Information

Reprints: Sandra M. Brown, MD, Department of Ophthalmology and Visual Sciences, Texas Tech University Health Sciences Center, Sixth and Flint, Lubbock, TX 79430 (

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