Pilot Study of the Incidence of Constitutional Chromosomal Abnormalities in a Community Clinic Setting

Constitutional chromosomal abnormalities in apparently normal individuals have shown a rise in incidence possibly because of improved banding techniques. Constitutional pericentric inversion of chromosome 9 [inv(9)] occurs in approximately 0.8%–2% of the normal population (Hsu et al. Am J Med Genet 1987, Tawn et al. Mutat Res 1992) and is generally regarded as a normal variant, as is constitutional pericentric inversion of chromosome 2 [inv(2)] (Hysert et al. Prenat Diagn 2006). However, both inversions have been implicated with infertility, recurrent spontaneous abortion, as well as myeloid leukemias (Daya. Curr Opin Obstet Gynecol 1994, Mozziconacci et al. Cancer Genet Cytogenet 1998). Inv(9) has also been implicated in causing delayed engraftment after autologous and allogeneic transplantation from donors with inv(9), though not without controversy (Keung et al. Br J Haematol 2003, Lee et al. Ann Clin Lab Sci 2010). Most of these studies were conducted among patients with leukemia and/or transplantation. To investigate the constitutional chromosomal abnormalities in a more community-like setting, we conducted a pilot study of the incidence of constitutional chromosomal abnormalities in our clinic.

Between January 2010 and June 2011, 248 consecutive patients, 132 males and 116 females, median age of 68.6 (range 20.5–89.5) underwent bone marrow examination for various indications at our clinic. Of these patients, 181 underwent one or more cytogenetic analysis. We then reviewed clinical charts.

A total of 274 bone marrow examinations were performed. Of the 274 bone marrow examinations, 199 conventional karyotypes were also obtained. Three patients (1.7%) with constitutional chromosomal abnormalities were found: two had pericentric inversion of chromosome 9, inv(9)(p12q13)_c, and one had pericentric inversion of chromosome 2, inv(2)(p11.2q13)_c.

Case 1. A 48-year old male presented with cryptococcal meningitis, absolute CD4 count of 3/μL and CD8 count 4/μL. He was treated successfully with high dose fluconazole. Subsequent workup suggested a diagnosis of idiopathic non-HIV CD4 lymphocytopenia (Smith et al N Engl J Med 1993). Bone marrow examination showed normal finding and no evidence of lymphoma, with 46,XY,inv(9)(p12q13)_c[20].

Case 2. A 66-year old female presented with asymptomatic leukocytopenia for 6 years, WBC 3,100-3,900/μL with normal hemoglobin and platelet. Bone marrow examination showed normal finding, with 46,XX,inv(9)(p12q13)_c[20].

Case 3. A 69-year old male presented with asymptomatic lymphocytosis, WBC 17,800/μL, Hgb 13.5 g/dL, platelet 227,000/μL, with neutrophils 27%, lymphocytes 68%, and monocytes 4%. Bone marrow examination diagnosed chronic lymphocytic leukemia, CD5+, CD19+ and CD23+, with 49,XY,inv(2)(p11.2q13), +12,+18,+19[2]/46,XY, inv(2)(p11.2q13)_c[18].

The incidence of constitutional chromosomal abnormalities is estimated to be 1.7% in this pilot study, which is similar to the reported literature. The occurrence of constitutional abnormalities in our patients may simply be coincidental. However, due to small sample size, a larger study is required to confirm this finding.

No relevant conflicts of interest to declare.