Treatment of Schizophrenia by Clozapine in an Adolescent Girl with DiGeorge Syndrome

Introduction

DiGeorge Syndrome (DGS) is a genetic disorder characterized by the 22q11 deletion. Clinical features are aplasia of thymus, hypoparathyroidism, cardiac defects, and dysmorphic face. It is common and seen in 1/4000 of live births. Psychiatric disorders are highly comorbid with a ratio of 40%–80% (Roukas et al. 2006). DGS and schizophrenia share the same genetic locus, which leads to higher prevalence of psychotic disorders particularly schizophrenia (Gothelf et al. 2007). Early onset schizophrenia (EOS) is considered as treatment resistant, in which clozapine is especially recommended (Schneider et al. 2015). Here we present a case with DGS and EOS whose psychotic symptoms were decreased by clozapine.

Case

A 15-year-old girl was brought to the child psychiatry outpatient clinic after she had tried to jump from a balcony to kill herself. She also had insomnia and fear of her grandfather and neighbors, because she believed that they would kidnap and harm her. Her psychiatric complaints had started 2 years ago. Her persecutory delusions that her parents would kill her and auditory halucinations “hearing a man's voice giving orders” were reported. She was diagnosed with a psychotic disorder. Her previous medications were first risperidone 4 mg/day, then paliperidone 6 mg/day, and finally aripiprazole 20 mg/day. From her medical history, it was noticed that she was diagnosed with DGS when she had hypocalcemic convulsions on the 3rd day of her birth. She had aplasia of thymus, hypoparathyroidism, unilateral kidney aplasia, and dysmorphic face. She was moderately mentally retarded (total IQ:48) and she was going to a special education center.

We considered EOS as her diagnosis. Due to the fact that her symptoms were decreased only 30% and she had experienced a suicide attempt, and another reason was the insufficient effects of the risperidone, paliperidone, and aripiprazole use, clozapine was chosen after consent was obtained from her parents. Her baseline ECG, leucocyte and absolute neutrophil count (ANC), and liver enzymes test were obtained. Her baseline Clinic Global Impressions-Severity (CGI-S) score was 6. The dose was started with 12.5 mg and titrated up to 200 mg in 2 weeks, and then up to 200 mg twice a day (400 mg/day) in 2 months. Weekly ANC and leucocyte counts were normal. She experienced a generalized tonic–clonic convulsion once during 500 mg/day clozapine treatment in the eighth month. However, her EEG was normal, clozapine was lowered to 250 mg/day, and valproic acid (500 mg/day) was added as an antiepileptic prophylaxis (Williams and Park 2015). Now she has been on clozapine treatment for 2 years. Her endpoint CGI-S is 2 and her clinical state is “very much improved.” No serious side effects except some sialorrhea and mild sedation were observed. Ipratropium spray was used in case of increase in sialorrhea.

Discussion

Psychotic disorders comorbid with DGS are more resistant to traditional antipsychotics (Gothelf et al. 2007). In case of treatment resistance and accompanying suicidal behaviors in schizophrenia, clozapine is considered as gold standard (Scheider et al. 2015). We showed that in severe cases like EOS in DGS, precautious use of clozapine is effective, which is consistent with the adult data (Butcher et al. 2015). Clinicians must bear in mind that antiepileptics are added to higher doses of clozapine to prevent seizures (Williams and Park 2015).