Achandira M. Udayakumar

Complex t(8;13;21)(q22;q14;q22)–A Novel Variant of t(8;21) in a Patient with Acute Myeloid Leukemia (AML–M2)

Variants of the t(8;21)(q22;q22) involving chromosome 8, 21, and other chromosomes account for about 3% of all t(8;21)(q22;q22) in acute myeloid leukemia (AML) patients. We report a case of AML-M2 with t(8;13;21)(q22;q14;q22), not reported earlier. Using a dual-color fluorescence in situ hybridization (FISH) analysis with ETO and AML1 probes, we demonstrate an ETO/AML1 fusion signal on the derivative chromosome 8. Whole chromosome painting probes were used for chromosomes 8 and 13, to demonstrate the three-way translocation t(8;13;21)(q22;q14;q22). Involvement of chromosome region 13q14 has never been reported earlier, although region 13q12 as a variant in AML with t(8;21) has been reported earlier. The possible role of genes in this region in leukemogenesis, its response to the treatment and its clinical implications are discussed.

Acquired pericentric inversion of chromosome 9 in acute myeloid leukemia

Pericentric inversion of chromosome 9 involving the qh region is relatively common as a constitutional genetic aberration without any apparent phenotypic consequences. However, it has not been established as an acquired abnormality in cancer. Among the three patients reported so far in the literature with acquired inv(9), only one had acute myeloid leukemia (AML). Here we describe an unique case where both chromosomes 9 presented with an acquired pericentric inversion with breakpoints at 9p13 and 9q12 respectively, in a AML patient with aberrant CD7 and CD9 positivity. Additionally, one der(9) also showed short arm deletion at 9p21 to the centromeric region and including the p16 gene. The constitutional karyotype was normal. This is probably the first report describing an acquired inv(9) involving both chromosomes 9 in AML. The possible significance of this inversion is discussed.

Constitutional trisomy 8 mosaicism syndrome: case report and review.

Trisomy 8 mosaicism (Warkany syndrome) is a rare viable condition with variable phenotypes, ranging from mild dysmorphic features to severe malformations. Karyotyping and fluorescence in-situ hybridization potentially help detecting this low mosaic clone to confirm the diagnosis of patients with classical and unusual clinical presentations. This report reviews few previous cases to describe our case - a boy who had trisomy 8 mosaicism with severe dysmorphic features, born to a consanguineous Arabic couple. This study concludes that careful cytogenetic diagnoses of trisomy 8 mosaicism is essential for appropriate management and follow up of this rare disorder.

Cytogenetic, clinical, and hematological features of pediatric myelodysplastic syndrome in Oman

Childhood myelodysplastic syndrome (MDS) is uncommon and its incidence is 1.8–4 cases per million with a frequency of 6–9% [1,2]. Karyotype abnormalities are present in 30–50% with monosomy 7 as a common marker [3]. We are presenting data on 11 Omani children with MDS (excluding Downs) who presented to our hospital between 2003 and 2013. Patient demographics, clinical characteristics, and cytogenetic findings are shown in Table I. A minimum of 20 metaphases were analyzed from unstimulated bone marrow (BM) cultures. Monosomy 5 and 5qare uncommon in children [4]. The frequency ofmonosomy 7 and trisomy 8 in our patients were similar to those reported previously [3–5]. Cytogenetics is an important predictor of prognosis [6]. Abnormal karyotypes observed in 54% of our patients are in agreement with previous publications [3]. The age range was slightly higher compared to other reports but the male/female distribution was similar [1,2,5,7]. Blast percentage is a critical morphological parameter for classifying MDS [6]. The proportion of patients with low BM blast counts was higher in our group as compared to 40% reported elsewhere [7]. Five patients (45%) showed multilineage dysplasia, for which the significance is unknown [4]. Increases in levels of HbF [4] and ferritin were as reported previously. White blood counts were low to normal, and absolute neutrophil and platelets counts were on at lower end of the normal range (Table I). Previous studies showed half of affected children with similar results [7]. Mild to moderate hepatomegaly in seven patients and multilineage dysplasia in five patients were observed. Survival of>5 years was observed in five (45%) patients. The longest survival observed was 95 months (Supplementary Table SI). Patients with normal karyotype (NK) andmonosomy 7were less frequent than the 59% reported from Japan [8]. Of the 61% cytogenetic abnormalities reported in a review of 610 patients, 60% had only single abnormality [5,7–9]. Our patients showed 54% cytogenetic abnormality and all were single abnormalities. Among our patients who underwent hematopoietic stem cell transplantation (HSCT), four (36.4%) showed survival of 52, 60, 69, and 63months. Patients with monosomy 7 have a significantly higher probability of progression to advancedMDS than patients with other chromosome abnormality or NK [7]. Three of our patients who had monosomy 7 (27%) transformed to leukemia, but among those who had NK, two are alive, with an overall survival of >5 years (95 and 60 months) and those patients have not gone into leukemia. The longest survival in our group with NK is nearly’8 years (95months). A patient who had þ8/NK is still surviving after 69 months. In our group, compared to reports from other populations, we found more variation in frequency of abnormalities, differences in the median age of presentation, more patients with low blast percentage, and fewer patients with NK. HSCT was associated with good survival.

Myelodysplasia progressing to acute myeloid leukemia in monozygotic twins with monosomy 7 as sole abnormality

1 Cytogenetics Unit, Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Sultanate of Oman, 2 Pediatric Hematology Unit, Department of Child Health, Sultan Qaboos University Hospital, Muscat, Sultanate of Oman and 3 Pediatric Hematology Unit, Department of Child Health, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Sultanate of Oman

A rare case of de novo mosaicism: Deletion 18p and isochromosome 18q syndrome

Monosomy 18p syndrome is a rare chromosomal disorder with varying phenotypic and clinical manifestations. Dysmorphism, growth delay, delayed speech and mental retardation are a few of the commonest features observed. The cytogenetic findings also vary and may comprise a pure deletion of the entire 18p arm or a deletion of a part of the 18p arm, if involved in a translocation with other chromosomes. Monosomy 18p may either occur by itself or with a structural alteration of the remaining chromosome 18, as a ring or as an isochromosome. The clinical presentation of this syndrome often overlaps with other syndromes. Establishing a cytogenetic diagnosis and understanding the location of the breakpoints is crucial for precise management and follow-up. We present here a rare case with mosaicism for a de novo deletion of 18p with isochromosome 18q in a boy born to a consanguineous Omani couple.