How to diagnose the 22q11.2 deletion syndrome in patients with schizophrenia: a case report

Abstract

The 22q11.2 deletion syndrome is caused by a microdeletion of chromosome 22. One third of all patients with 22q11.2 deletion develop schizophrenia-like symptoms. In general, the prevalence of 22q11.2 deletion in patients with schizophrenia is 1%-2%. The 22q11.2 deletion is one of the major known genetic risk factors for schizophrenia. However, clinical differences in the phenotypes between patients with schizophrenia who are 22q11.2 deletion carriers and those who are not are still unknown. Therefore, it may be difficult to diagnose 22q11.2 deletion in patients with schizophrenia on the basis of clinical symptoms. To date, only two Japanese patients with the deletion have been identified through microdeletion studies of patients with schizophrenia in the Japanese population. Herein, we report the case study of a 48-year-old Japanese woman with 22q11.2 deletion who had a 30-year history of schizophrenia. Based on craniofacial anomalies, unpredictable agitation, hypocalcemia, and brain imaging finding, we suspected the 22q11.2 deletion in clinical populations and diagnosed the deletion using fluorescence in situ hybridization analysis. To find common phenotypes in Japanese patients with the deletion who have schizophrenia-like symptoms, we compared phenotypes among three Japanese cases. The common phenotypes were an absence of congenital cardiovascular anomalies and the presence of current findings of low intellectual ability, agitation, and hypocalcemia. We propose that hypocalcemia and agitation in patients with schizophrenia may derive from the 22q11.2 deletion, particularly when these phenotypes are coupled with schizophrenia-like symptoms.

Figure 1

Features of a 48-year-old woman with the 22q11.2 deletion. (a) Past history of an operation for cleft palate. (b) Mild dysmorphic facial features, including a low anterior hairline, swollen eyelids, malar flatness, nose with a bulbous nasal tip, hypoplastic nasal alae and a square and flat nasal root, small mouth, and a thin upper lip. (c) Basal ganglia calcification due to hypocalcemia. (d) Fluorescence in situ hybridization; red and green regions were detected by TUPLE1 (22q11.2) and ARSA (22q13.3) probes, respectively. The arrow and arrowhead indicate expected red and green regions, respectively. One chromosome 22 with the deletion of TUPLE1 (22q11.2) was detected.