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Psychotic illness in people with Prader-Willi syndrome: a systematic review of clinical presentation, course and phenomenology.

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Lester, Suzannah D 
Holland, Anthony J 
Fletcher, Paul C 


BACKGROUND: Prader-Willi syndrome (PWS) is a rare and complex neurodevelopmental disorder resulting from absent paternal expression of maternally imprinted genes at chromosomal locus 15q11-13. This absence of expression occurs as a consequence of a deletion on the chromosome 15 of paternal origin (ca. 70%), a chromosome 15 maternal uniparental disomy (mUPD; ca. 25%), or an imprinting centre defect (IC; ca. 1-3%). At birth, individuals with PWS are severely hypotonic and fail to thrive. Hyperphagia and characteristic physical and neuropsychiatric phenotypes become apparent during childhood. The risk for the development of a co-morbid psychotic illness increases during the teenage years, specifically in those with PWS due to the presence of an mUPD. The primary aim of this literature review is to inform clinical practice. To achieve this, we have undertaken a systematic analysis of the clinical research literature on prevalence, presentation, course, characteristics, diagnosis and treatment of psychotic illness in people with PWS. The secondary aim is to identify clinical aspects of psychotic illness in PWS in need of further investigation. METHODS AND FINDINGS: A systematic literature review on psychosis in PWS was conducted on the databases Web of Knowledge, PubMed and Scopus, using the terms "((Prader-Willi syndrome) OR (Prader Willi Syndrome)) AND ((psychosis) OR (psychotic illness))". All articles written in English and reporting original human research were reviewed. In all but three of the 16 cohort studies in which the genetic types were known, the authors reported higher rates of psychosis in people with PWS resulting from an mUPD, compared to those with the deletion subtype of PWS. When psychosis was present the presentation was psychosis similar regardless of genetic type and was usually characterised by an acute onset of hallucinations and delusions accompanied by confusion, anxiety and motor symptoms. CONCLUSIONS: The onset of confusion, an affective cyclical pattern with the presence of abnormal mental beliefs and experiences, usually of rapid onset is suggestive of the development of psychotic illness. Phenomenologically, this psychosis in people with PWS is atypical in comparison to schizophrenia and bipolar disorder in the general population. The relationship to psychosis in the general population and the optimum treatments remain uncertain.


Acknowledgements: We would like to thank Dr Katherine Manning for her input, and our funder Sam’s research foundation.

Funder: the Bernard Wolfe Health Neuroscience Fund

Funder: the NIHR Applied Research Collaboration East of England


Atypical psychosis, Cycloid psychosis, Delusion, Early onset psychosis, Genetic origin of psychosis, Hallucination, Prader–Willi syndrome, Psychosis, Adolescent, Infant, Newborn, Humans, Prader-Willi Syndrome, Psychotic Disorders, Comorbidity, Family, Anxiety, Chromosomes, Human, Pair 15

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Orphanet J Rare Dis

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Springer Science and Business Media LLC
Wellcome Trust (206368/Z/17/Z)