Co-Occurrence of Pallister-Killian Syndrome and Burkitt Lymphoma in a Patient with Near-Normal Neurocognitive Development

Abstract

Background: Pallister-Killian syndrome (PKS) is typically recognized by its features that include developmental delay, seizures, sparse temporal hair, and facial dysmorphisms. PKS is most frequently caused by mosaic supernumerary isochromosome 12p.

Case presentation: Here, we report a patient with PKS who was subsequently diagnosed with Burkitt lymphoma. Following the successful treatment of lymphoma, this patient demonstrated very mild intellectual disability despite the diagnosis of PKS, which is usually associated with severe developmental delay.

Discussion: This is the first reported patient with PKS and a hematologic malignancy. Although there is no significant reported association of tetrasomy 12p with cancer, the co-occurrence of two rare findings in this patient suggests a potential relationship. The localization of AICDA, a gene for which overexpression has been implicated in promoting t(8;14) noted in our patient's lymphoma, raises a potential mechanism of pathogenesis. In addition, this case indicates that children with PKS can demonstrate near-normal cognitive development.

Keywords: Burkitt lymphoma; Dysmorphia; Hyperpigmentation; Mosaic; Pallister-Killian syndrome; Teschler-Nicola-Killian syndrome; Tetrasomy 12p.

Fig. 1.

Facial features of the proband with PKS. a Facial features at 29 months include epicanthal folds, a short upturned nose, and downturned corners of the mouth. b Facial features at a recent evaluation demonstrate mild coarse facial features, sparse anterior scalp hair, mild bilateral ptosis, infraorbital ceases, mild anteversion of the nares, and smooth philtrum with thin upper lip. Written consent was obtained for the use of the clinical pictures of the proband.

Fig. 2.

SNP array results of blood and skin tissue samples. a Hypopigmented skin tissue result. b Hyperpigmented skin tissue result. c Blood sample result. a, b Array results of the skin biopsy samples showing the presence of mosaicism for four copies of 12p, with three haplotypes at the distal end of the chromosome. c On the contrary, copy number alteration was not seen in the blood sample.

Fig. 3.

Cytological findings of lymphoma tissue sample. a Histology of lymphoma in ileum, ×100 magnification. Diffuse infiltrate of medium-sized cells with nonoverlapping nuclei. Vague starry sky appearance was observed. There are frequent mitoses (arrow), apoptotic nuclei (arrowhead), and tingible body macrophages (dashed arrow). Tumor cells are positive for CD79a (B-cell marker). bIGH::MYC FISH demonstrated a fusion of IGH::MYC loci in the lymphoma tissue sample. Interphase FISH with a dual fusion probe set for the 8 centromere; MYC and IGH revealed a small clone with a reciprocal fusion between 8 and 14, fusing MYC and IGH. Vysis LSI IGH/MYC/CEP 8 Tri-Color Dual Fusion FISH Probe Kit was used. 8p11.1-q11.1 CEP8 alpha satellite SpectrumAqua probe, 8q24 LSI MYC SpectrumOrange, and 14q32 LSI IGH SpectrumGreen probes were used. Arrows indicate the fusion signals of IGH::MYC fusion.