A Phenotypically Normal Patient with Constitutional Trisomy 8 Mosaicism and AML
Some chromosomal abnormalities can be observed as both acquired or constitutional, one such example is trisomy 8. As an acquired abnormality, +8 is one of the most common found in myeloid disorders. As a constitutional one, it is a rare abnormality, almost always seen in mosaic form, and may be confined to certain tissue types. Patients with constitutional trisomy 8 mosaicism (CT8M) exhibit a wide range of phenotypic features and also appear to be at increased risk of developing certain solid tumours and haematopoietic malignancies. A 27 year-old woman, previously diagnosed with AML (presentation karyotype unknown), presented to us to ascertain her remission status post chemotherapy. Cytogenetic analysis revealed the presence of trisomy 8 in all 20 bone marrow cells examined, however, all other tests indicated complete remission. An extra chromosome 8 was also detected in 87% of cells by fluorescence in situ hybridisation (FISH). Cytogenetic examination of TPA and PHA stimulated peripheral blood revealed that in both cultures, the majority of cells had trisomy 8, however, FISH and chromosome analysis of skin did not yield any cells with +8. The patient was referred to a clinical geneticist, who confirmed she was of normal intelligence and showed none of the physical stigmata of CT8M, though she has had 3 miscarriages. She remains in remission 28 months post diagnosis. Examination of genetic markers on chromosome 8 indicated that a postzygotic nondisjunction event had resulted in the gain, which is the most common mechanism for CT8M. Although cases of phenotypically normal CT8M are rare, the phenotype of some affected individuals can still be quite subtle. This, together with their apparently increased risk of myeloid neoplasms, emphasize the need for all potentially involved medical professionals to be aware that these cases exist, as the distinction between constitutional and acquired trisomy 8 can be critical.