Commentary on Treatment Resistant Psychosis in an adolescent with scoliosis and a history of early feeding difficulties

This case highlights the importance of recognizing 22q11 Deletion syndrome (22q11DS) in clinical psychiatric practice. Psychotic disorders are highly prevalent (25–30%) in patients with 22q11DS (Pulver et al. 1994; Murphy et al. 1999), and psychotic symptoms are even more common (26–48%) (Baker and Skuse 2005; Debbane et al. 2006; Vorstman et al. 2006). Among randomly selected patients with schizophrenia there is evidence of an increased prevalence of 22q11 deletions compared with the general population (2% versus 0.025 %, respectively) (Karayiorgou et al. 1995). Prevalence is higher (5–6%) among patients with childhood onset schizophrenia (Usiskin et al. 1999; Sporn et al. 2004). However, when individuals with schizophrenia are screened for the presence of clinical features consistent with 22q11DS, like in the current report, a much higher prevalence (14–53%) is found (Gothelf et al. 1997; Bassett et al. 1998). It is important to recognize that the phenotypic features of 22q11DS are highly variable and a diagnosis may be elusive during infancy, this is especially true for cases of the syndrome in which there is later onset of findings such as speech abnormalities, thrombocytopenia, osteopenia, and behavioral problems. In this regard there are three previously published cases in addition to the current report of psychotic symptoms leading to cytogenetic diagnosis of 22q11 microdeletion (Sieberer et al. 2005; Sieberer et al. 2006).

Clozapine in the treatment of psychosis in patients with 22q11DS has been previously suggested (Gothelf et al. 1999) in spite of the risk of agranulocytosis; however, it is not known whether there is a greater risk for this adverse event in 22q11DS. Poor response to conventional anti-psychotic medications - such as haloperidol used in the current report after the development of agranulocytosis - has been previously reported (Gothelf et al. 1999); yet others (Murphy et al. 1999; Bassett et al. 2003) published that response to anti-psychotics is similar in 22q11 deleted and non-deleted psychotic individuals. There is a need for systematic evaluation of the efficacy of anti-psychotics in large cohorts of 22q11DS.

Clinicians must have a high index of suspicion for 22q11DS among psychotic patients, especially when at least one of the following is present: learning disabilities, facial dysmorphology, palate anomalies, congenital heart disease, or hypocalcaemia.

Diagnosing this chromosomal abnormality has important implications for patient management, early recognition of conditions associated with 22q11DS, such as hypocalcaemia or hyperparathyroidism, allowing for improved treatment. In addition, it is an important consideration for family members who may be at risk given the 50% risk of transmitting the deletion to the next generation.