Patients with chromosome 22q11. 2 deletion syndrome (CH2211. 2qD) have multiple reasons to be at risk for malignancy, yet there are little data on the subject. CH22q11. 2D syndrome is an increasingly common haploinsufficiency syndrome. Current estimates are that the spontaneous deletion rate approximates 1: 4,000, however, many more patients are reaching adulthood than was previously possible and increasing familial transmission accounts for the rising incidence [Devriendt et al., 1998; McDonald-McGinn et al., 2001]. Given the high frequency of this syndrome in the population, it is extremely important to define the risk of malignancy. Previous reports of malignancy arising in patients with CH22q11. 2D syndrome have suggested that malignancy may be increased in patients with severe T-cell compromise or in older literature, with the phenotype known as DiGeorge syndrome [Asamoto and Furuta, 1977; Tewfik et al., 1977; Ramos et al., 1999; Sato et al., 1999a; Hong et al., 2001]. Patients with serious T-cell defects regardless of the specific immunodeficiency have an increased risk of lymphoma. It also appears to be the case that chronic inflammation which could occur as a consequence of infection predisposes to malignancy in some populations [O’Byrne and Dalgleish, 2001]. Finally, the hemizygous deletion generally includes the catechol-O-methyltransferase gene (COMT). Alterations in COMT function have been associated with an impaired ability to detoxify certain environmental carcinogens [Dawling et al., 2001; Hung et al., 2004]. Thus, there are at least three possible reasons for patients to have an increased risk of malignancy. The immunodeficiency in patients with CH22q11. 2D ranges from profound with an absent thymus and no circulating T cells to completely normal [Barrett et al., 1981; Bastian et al., 1989; Ryan et al., 1997; Jawad et al., 2001]. With age, patient T-cell numbers typically approach normal, although the repertoire is not as robust and there is some decline in proliferative responses with increasing age [Jawad et al., 2001; Piliero et al., 2004]. This fairly subtle immunodeficiency would not be expected to predispose to malignancy in a significant fashion. Nevertheless, the broad range of immunodeficiency suggests that there may be a contribution in some cases.

Few case reports of patients with CH22q11. 2D syndrome and malignancy have been published. This may reflect under-ascertainment or a true lack of relationship between the two processes. As described above, patients with either CH22q11. 2D syndrome and severe immunocompromise, or in older studies, DiGeorge syndrome, had a clearly increased risk of lymphoma, particularly B-cell lymphoma [Ramos et al., 1999; Sato et al., 1999b; Hong et al., 2001]. This is a general phenomenon in patients with severe immunodeficiency. There have also been reports of myelodysplasia, squamous cell carcinoma, glioma, neuroblastoma, hepatoblastoma, and renal cell carcinoma [Asamoto and Furuta, 1977; Tewfik et al., 1977; Patrone et al., 1990; Scattone et al., 2003; Ozbek et al., 2004]. In an effort to obtain better