(056) A case of catatonia in White-Sutton syndrome

Abstract: A case of catatonia in White-Sutton syndrome

Background:
White-Sutton Syndrome is a neurodevelopmental disorder caused by a pathogenic variant of the pogo transposable element with zinc finger domains (POGZ). While the clinical phenotype has been well described, little is known about the psychiatric comorbidities of this disorder.

Case:
Patient is a 58-year-old female with a history of intellectual disability who was brought to the emergency department for a gradual decline in cognitive function, withdrawn behaviors, and incontinence. She had no psychiatric history until several months prior when she developed depressive symptoms and was started on citalopram and paliperidone. Soon after starting these medications, she became disheveled and began responding to unseen others, so she was admitted to a psychiatric hospital where oral paliperidone was transitioned to paliperidone LAI. Cognitive function worsened after discharge, prompting her presentation to the emergency department. Examination revealed a patient with short stature, hypertelorism, retrognathia, and microcephaly and she exhibited numerous signs of catatonia. She was admitted to the hospital where she was started on lorazepam and both citalopram and paliperidone were stopped. Catatonic symptoms improved and she was discharged with outpatient follow-up. Over the course of several months, patient began to exhibit a recurrence of catatonic symptoms requiring reinitiation of benzodiazepines. Given the patient’s atypical presentation, whole genome sequencing was conducted that identified patient was heterozygous for a pathogenic variant in the POGZ gene, consistent with White-Sutton syndrome. To date, patient has regular psychiatric follow-ups to monitor for signs of catatonia and is managed on clonazepam and amantadine.

Discussion:
POGZ is located on chromosome 1q21.3 and is involved in kinetochore assembly, mitotic sister chromatid cohesion, and mitotic chromosome segregation (Nozawa, 2010). Mutations in the POGZ gene correlate with cognitive dysfunction, developmental delays, autism spectrum disorder, hypotonia, and craniofacial abnormalities (White, 2016). Since this patient's catatonia followed the introduction of an antipsychotic, it is possible that POGZ may play a role in dopamine regulation and catatonia. Further research may elucidate the role of POGZ in the metabolism of psychotropic medications and therefore help to guide treatment.

Conclusions:
The presence of catatonia in the described patient with White-Sutton syndrome adds to our understanding of this syndrome’s psychiatric comorbidities and potentially implicates the role of POGZ in the pathogenesis of catatonia.

References:
POGZ truncating alleles cause syndromic intellectual disability. White et al. Genome Medicine 2016.
Human POGZ modulates dissociation of HP1alpha from mitotic chromosome arms through Aurora B activation. Nozawa et al. Nature Cell Biology 2010.