Unexplained Pancytopenia in a Patient with 5q35.2-q35.3 Microduplication Encompassing NSD1: A Case Report

  • Sungwoo Park Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
  • Gyeong-Won Lee Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
  • Eun-Ha Koh Department of Laboratory Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
  • Hyun-Young Kim Department of Laboratory Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
Keywords: Pancytopenia, Chromosomal abnormality, Microarray

Abstract

The 5q35.2-q35.3 duplication phenotype is characterized by growth delay, microcephaly, mental retardation and delayed bone aging. However, there has been no reports on the occurrence of pancytopenia as a consequence of 5q35.2-q35.3 duplication. A 42-year-old male visited the emergency room due to multiple trauma. He had been diagnosed with mental retardation in the past. No previous history of severe bleeding symptom was also reported . Complete blood cell counts were leukocyte 3.51×109/L, neutrophil 0.19×109/L, hemoglobin 8.3 g/dL, hematocrit 25.0%, and platelet 4.0×109/L. There was no relevant history of any medication intake and there were no other haematological parameters leading to the persistent pancytopenia. A bone marrow biopsy revealed hypercellular marrow with increased trilineage hematopoiesis. The uptake of fluorodeoxyglucose was increased in multiple lymph nodes, bone and spleen in positron emission tomography–computed tomography. A biopsy of the right axillary lymph node was performed and histologic findings were unremarkable. The chromosomal microarray revealed a 3.46 Mb microduplication at the 5q35.2-q35.3 site including NSD1. The patient had distinctive features related to atypical pancytopenia. Various managements for pancytopenia had no effect on the patient. However, there were no complications such as massive bleeding or serious infection compared to the severity of pancytopenia during a follow-up of 3 months. In addition, periodic patterns of deterioration and improvement in pancytopenia appeared spontaneously. Since it is rare for these distinctive features of pancytopenia and chromosomal abnormality to coexist, it is important to investigate the association. In the current study, we describe the first case of 5q35.2-q35.3 microduplication encompassing NSD1 with unexplained pancytopenia.

References

Weinzierl EP, Arber DA. The differential diagnosis and bone marrow evaluation of new-onset pancytopenia. Am J Clin Pathol 2013;139:9-29.

Jha A, Sayami G, Adhikari RC, Panta AD, Jha R. Bone marrow examination in cases of pancytopenia. JNMA J Nepal Med Assoc 2008;47:12-7.

Tatton-Brown K, Douglas J, Coleman K, Baujat G, Cole TR, Das S, et al. Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations. Am J Hum Genet 2005;77:193-204.

Chen CP, Lin SP, Lin CC, Chen YJ, Chern SR, Li YC, et al. Molecular cytogenetic analysis of de novo dup(5)(q35.2q35.3) and review of the literature of pure partial trisomy 5q. Am J Med Genet A 2006;140:1594-600.

Weinreb NJ, Rosenbloom BE. Splenomegaly , hypersplenism , and hereditary disorders with splenomegaly. Open Journal of Genetics 2013;3:24-43.

Hollak CE, Belmatoug N, Cole JA, Vom Dahl S, Deegan PB, Goldblatt J, et al. Characteristics of type I Gaucher disease associated with persistent thrombocytopenia after treatment with imiglucerase for 4-5 years. Br J Haematol 2012;158:528-38.

Zhu A, Lee D, Shim H. Metabolic positron emission tomography imaging in cancer detection and therapy response. Semin Oncol 2011;38:55-69.

Dikow N, Maas B, Gaspar H, Kreiss-Nachtsheim M, Engels H, Kuechler A, et al. The phenotypic spectrum of duplication 5q35.2-q35.3 encompassing NSD1: Is it really a reversed sotos syndrome? American Journal of Medical Genetics, Part A 2013;161:2158-2166.

Rosenfeld JA, Kim KH, Angle B, Troxell R, Gorski JL, Westemeyer M, et al. Further evidence of contrasting phenotypes caused by reciprocal deletions and duplications: Duplication of NSD1 causes growth retardation and microcephaly. Molecular Syndromology 2012;3:247-254.

Kenny J, Lees MM, Drury S, Barnicoat A, Van't Hoff W, Palmer R, et al. Sotos syndrome, infantile hypercalcemia, and nephrocalcinosis: a contiguous gene syndrome. Pediatr Nephrol 2011;26:1331-4.

Published
2018-10-03
How to Cite
1.
Park S, Lee G-W, Koh E-H, Kim H-Y. Unexplained Pancytopenia in a Patient with 5q35.2-q35.3 Microduplication Encompassing NSD1: A Case Report. ijhoscr. 12(4):259-63.
Section
Case Report(s)