Malignant catatonia represents a severe and life-threatening neuropsychiatric syndrome that demands prompt recognition and intervention. This condition poses particular diagnostic and management challenges in adolescents, especially when genetic predispositions and neurodevelopmental vulnerabilities complicate the clinical picture.

This report examines a complex case of malignant catatonia in a 17-year-old female with developmental delay but no prior psychiatric diagnoses, who developed severe cognitive and behavioural deterioration. We explore the diagnostic complexities, therapeutic challenges and potential genetic contributions to her presentation.

We present a comprehensive case analysis documenting clinical progression, treatment responses and genetic findings through whole-exome sequencing. The patient’s journey spans from initial presentation to long-term follow-up, with systematic assessment using standardised catatonia rating scales.

The patient’s condition manifested as severe psychomotor impairment, mutism and autonomic instability, showing minimal response to initial treatment. Electroconvulsive therapy yielded significant but temporary amelioration of symptoms. Genetic analysis revealed a heterozygous mutation in the pogo transposable element derived with zinc finger domain (POGZ) gene – a gene implicated in neurodevelopmental disorders – suggesting this variant contributed to her neurobiological vulnerability. Concurrent features of functional neurological disorder further compounded the diagnostic complexity, illustrating the intricate interplay between genetic susceptibility and clinical presentation.

This case illuminates the challenges clinicians face when diagnosing and treating complex neuropsychiatric presentations in adolescents, particularly when genetic predispositions intersect with functional neurological symptoms. The findings emphasise how comprehensive, multidisciplinary approaches remain essential for optimal patient care. Moreover, this case highlights the selective utility of genetic investigation in elucidating potential underpinnings of complex, treatment-resistant malignant catatonia, whilst demonstrating that genetic variants may confer vulnerability rather than direct causation.

Evidence indicates that classical antipsychotics may aggravate non-malignant and malignant catatonia (MC). Atypical antipsychotics are less likely to cause movement disorders than classical antipsychotics and they are being frequently prescribed in disorders that can be associated with catatonia. Therefore, the important question that arises is whether atypical antipsychotics have a role to play in the treatment of catatonia.

A Medline search was performed to locate papers on the use of atypical antipsychotics in catatonia published between 1970 and 31st December 2004.

The literature on the use of atypical antipsychotics in catatonia consists of case reports and retrospective studies. In most cases of non-MC a reduction of the catatonic symptoms is reported upon treatment with atypical antipsychotics. Cases of MC relate mainly to the neuroleptic malignant syndrome (NMS), which is considered as an iatrogenic stuporous variant of MC caused by antipsychotics.

There are indications that atypical antipsychotics may be useful in non-MC. As a consequence, one should not only focus on the possible extrapyramidal and autonomic side effects of these drugs, but also on the possible beneficial effects on certain brain functions and on the catatonic symptomatology. However, randomized controlled trials are needed to evaluate the effect of these drugs, and caution is advisable, since cases of NMS have been linked to treatment with atypical antipsychotics. There is no evidence to prescribe atypical antipsychotics in MC.