Molecular karyotyping is important in determining the cause of behavioural phenotypes

Abstract

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.