Pallister-Killian syndrome is a rare, multi-system developmental diagnosis typically caused by tetrasomy of chromosome 12p that exhibits tissue-limited mosaicism. The spectrum of clinical manifestations in Pallister-Killian syndrome is wide and includes craniofacial anomalies, clefts, ophthalmologic, audiologic, cardiac, musculoskeletal, diaphragmatic, gastrointestinal, genitourinary, and cutaneous anomalies in association with intellectual disability and seizures. Growth parameters are often normal to elevated at birth with deceleration of growth postnatally. No formal estimate of the prevalence of Pallister-Killian syndrome has been made. Here, we report the clinical findings in 59 individuals with Pallister-Killian syndrome who were ascertained at Pallister-Killian syndrome Foundation family meetings held in the summers of 2006, 2008, 2009, and 2010. In addition, the clinical findings of 152 cases reported in the medical literature were reviewed and compared to the cohort examined here. Several novel clinical characteristics were identified through detailed dysmorphology examinations of this cohort and reassertion of a mild developmental variant is described. This report expands the clinical manifestations of Pallister-Killian syndrome and highlights the variable expressivity of this diagnosis with important implications for diagnosis and counseling.

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.

The Pediatric Symptom Checklist-17 (PSC-17) is a brief form of the Pediatric Symptom Checklist that is designed to screen for behavioral health problems in primary care settings. It has been proposed to have three subscales: externalizing, internalizing, and attention problems. In the context of developing a behavioral health screening program in an inner-city primary care practice, we evaluated the construct validity of the PSC-17. A total of 331 families with children between 4 and 12 years of age who were seen for well-child care during the study were invited to complete the PSC-17 and 320 families (96.5%) did so. A confirmatory factor analysis was performed and the Comparative Fit Index and root mean square error of approximation fit statistics were calculated to determine whether the data fit the proposed three-factor model. We found that although the PSC-17 contained three subscales, several items did not load predominantly on the subscale that they were proposed to measure. Specifically, although the five items on the internalizing subscale loaded only on this subscale, only four of the seven externalizing items loaded exclusively on the externalizing subscale, and only two of the five attention items loaded exclusively on the attention problems subscale. Clinicians using the PSC-17 in urban low-income communities should recognize that the externalizing and attention problems subscales of the PSC-17 may not be valid measures of these dimensions of child behavior in this population.