Developmental and behavioral characteristics of individuals with Pallister–Killian syndrome

Abstract

Pallister-Killian syndrome is a sporadic disorder caused by the presence of mosaic tetrasomy of the short arms of chromosome 12. Case reports of children with Pallister-Killian syndrome have described a range of developmental and behavioral outcomes, but no systematic studies of these outcomes exist. The objective of this study was to describe developmental and behavioral characteristics of individuals with Pallister-Killian syndrome participating in a national meeting of families and their affected children. Sixteen individuals with Pallister-Killian syndrome, ages 16 months to 19 years, were studied using questionnaires and direct interview. Among the 16 patients enrolled in the study, 3 probands were between 16 and 19 months, and had severe developmental delay. Among the rest of the 13 probands older than 24 months, 11 children had a developmental level of less than 8 months age equivalent. They were non-ambulatory, non-verbal, and passive, requiring extensive assistance in daily living. There were two higher functioning children who were ambulatory, and verbal. One of these children met criteria for Autism on the Autism Diagnostic Interview-Revised. Thus, although most individuals with Pallister-Killian syndrome studied showed profound intellectual disability and sensory impairments, individuals with Pallister-Killian syndrome can have mild to moderate intellectual disability. Therefore, in individuals with physical examination findings of Pallister-Killian syndrome, formal diagnostic testing should be considered, even in individuals with mild to moderate intellectual disability. Further studies will be needed to determine if these higher functioning children with Pallister-Killian syndrome are at increased risk for autism.

Pallister-Killian syndrome: a study of 22 British patients

“…No group report24 36 37 42–44 mentions the presence of hexasomic cell lines and these have only been recorded in 31 – 3 of 117 individually reported cases (2.6%). This may partly be explained by laboratories not actively seeking further low-level mosaicism once Pallister-Killian syndrome has been diagnosed.…”

“…A further six reported patients were able to walk and had some speech 1 23–26. One had an IQ of 811 and another of 69 24. One functioned at 24 month level at 6.5 years24 and one was in special needs education at the age of 7 years 25.…”

“…One had an IQ of 811 and another of 69 24. One functioned at 24 month level at 6.5 years24 and one was in special needs education at the age of 7 years 25. Few details are given on level of function in the other two cases 23 26.…”

“…Although the recent report from Wilkens et al 36 covers 59 affected individuals, each section covers only part of their cohort. Data on development and seizures is published in companion papers24 37 including 16 and 51 patients from their cohort, respectively. This study is the first to provide comprehensive data on a population based sample.…”

Mosaic chromosomal aneuploidy detection by sequencing (MAD-seq)

“…In those studies in which mosaic chromosomal aneuploidy was specifically sought, it was found to be associated with certain phenotypes, including several reports of mosaicism for chromosomal aneuploidy in peripheral blood in children with autism spectrum disorder (ASD). [16][17][18] Given the limitations of using blood to detect aneuploid cells, it is likely that mosaic chromosomal aneuploidy in ASD is not limited to these specific reported individuals but is more prevalent.…”