The Prader-Willi syndrome (PWS) is a genetically determined developmental disorder caused by abnormalities of the proximal region of chromosome 15q11-13. In a previous study, we reported that psychotic episodes, occurring in 16% of persons with PWS, had an onset in adolescence, never occurred in persons with paternal deletion, and were exclusively associated with maternal uniparental disomy (UPD) or imprinting abnormalities (IM). In order to gain a better understanding of the psychopathology and to further refine the psychiatric diagnosis, we describe in more detail the psychopathological manifestations of six adults with a history of psychotic episodes. All these individuals had a detailed psychiatric examination, including the use of the operational criteria (OPCRIT) checklist. An identifiable subtype of psychotic disorder was associated with PWS. Characteristics include early age of onset, acute onset, polymorphous, and shifting symptomatology and a need for psychiatric hospitalization. The presence of precipitating stress factors and a prodromal phase with physiological symptoms was reported in all patients. Current diagnostic categories do not allow an unequivocal psychiatric diagnosis.

In the present study we investigated the co-morbidity of pervasive developmental disorder (PDD) in 59 Prader-Willi syndrome (PWS) individuals and in 59 non-specific mentally retarded controls, matched for IQ, gender, and age. The 'Pervasive Developmental Disorder Mentally Retardation Scale' (PDD-MRScale), a screening questionnaire based on the DSM-III-R criteria for PDD, has been applied in the PWS group and in the control group. Results of the present study revealed a striking autistic-like behavioral phenotype in the majority of the PWS individuals, particularly deficits in the quality of language and communication and of imagination and interests. This intersection with autistic symptomatology is an important addition to the behavioral phenotype in PWS persons. A first approach to delineate subtypes of autistic symptomalogy among PWS persons was performed. Nineteen percent of the PWS group did meet the full diagnostic DSM-III-R criteria for PDD in comparison with 15% in the control group. Results revealed that a higher IQ in PWS does not protect to develop genuine PDD and that uniparental disomy/imprinting mutation as genetic origin seems to be an additional risk factor for developing genuine PDD. The results of the present study suggest the importance of reconsidering the commonly recognized obsessive-compulsive like behavior in PWS persons within the broader spectrum of autism disorders.

Prader-Willi syndrome (PWS) is a genetic disorder caused by the loss of the paternal contribution of the proximal part (15q11-q13) of the long arm of chromosome 15 (i.e. deletion, disomy and imprinting mutation). The syndrome is associated with distinct physical dysmorphism, as well as with specific behavioural and psychopathological characteristics. Psychiatric symptoms in adolescence and adulthood have been described, including acute cycloid psychosis, and obsessive compulsive, bipolar and pervasive developmental disorders. At the Centre for Human Genetics in Leuven, Belgium, 53 individuals (31 children and adolescents, and 22 adults) have been followed up for 15 years by a special multidisciplinary team. Attention was given to their medical, cognitive, behavioural and emotional development, and the evolution of psychiatric disorders in adolescence and adulthood. This study describes the psychiatric problems in four patients diagnosed with acute cycloid psychosis and traces their development from infancy to adolescence. Four other individuals needed psychiatric evaluation and treatment, and could be diagnosed as having unspecified bipolar disorder, also termed unstable mood disorder. Both groups were compared, and significant differences in early development and later evolution into adulthood were noted. The individuals with PWS who later developed psychotic episodes were described as active and extrovert toddlers, and showed autistic behaviour during their primary school education. Their intellectual functioning was in the moderate to severely retarded range. The individuals with PWS who later developed an unstable mood disorder were described as rather passive and introvert toddlers, and they presented less disturbed behaviour during their primary school education. The intellectual functioning of these subjects was in the normal to borderline range.

Background: The cytogenetic delineation and behavioural phenotype of syndromes has evolved from the chromosome level, through FISH (microdeletions syndromes, such as PWS, VCFS, SMS, del1p36) to molecular karyotyping (array CGH). The new syndromes being outlined in recent years account for rarer microdeletions and microduplications, in which the behavioural phenotype is not always well characterized. Method: We have screened by array CGH more than 2000 patients, of which almost 400 have cytogenetic imbalances. We present a subset of these patients, in which the behaviour was an important component of the motivation for molecular karyotyping. Results: Three case studies: 1) A boy with severe feeding problems, speech delay, stereotypic and autistic behaviour. He is dysmorphic and has an intellectual disability. Molecular karyotyping showed a de novo microdeletion of chromosome 15q13.2. 2) A 3‐year old girl with difficult behaviour, including negative vocalizations, aggression and repetitive rocking. She has poor weight gain, difficulty in falling asleep and wakes early. She is dysmorphic, has a developmental IQ of 67, a paternally inherited microdeletion of chromosome 9p21.3 and a de novo microduplication of chromosome 17p11.2. 3) A 5‐year old girl with intellectual disability who participates in interactive play but remains slow in task execution. Her balance is poor when standing and walking, She does not evidence satiety for food and constantly air‐swallows. Molecular karyotyping revealed a de novo microdeletion of chromosome 9qter. Conclusion: The molecular karyotyping results encourage its use in finding the cause of intellectual disability. With the assistance of international collaboration via common databases, such as Decipher, pinpointing and understanding the underlying genes contributing to the overall clinical picture, especially behaviour, will become a reality.