American Journal of Medical Genetics 128A:110–113 (2004) Cognitive and Adaptive Behavior Profiles of Children With Angelman Syndrome Sarika U. Peters, 1 * Jan Goddard-Finegold, 1 Arthur L. Beaudet, 2 Niru Madduri, 1 Marie Turcich, 1 and Carlos A. Bacino 2 1 Department of Pediatrics, Division of Developmental Pediatrics, Baylor College of Medicine & Texas Children’s Hospital, Houston, Texas 2 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas Angelman syndrome (AS) is a neurodevelopmen- tal disorder caused by maternal deficiency of the UBE3A gene that encodes E6-AP ubiquitin- protein ligase. Expression of the UBE3A gene from the maternal chromosome is essential to prevent AS. AS is characterized by severe mental retarda- tion, ataxia, and a defined behavioral pattern characterized mainly by happy/sociable disposi- tion. This study used the Bayley Scales of Infant Development and the Vineland Adaptive Beha- vior Scales to examine the cognitive abilities and adaptive behavior of children (n ¼ 20) with the four known molecular classes of AS, including patterns of strengths and weaknesses across adaptive behavior domains, and the relationship between adaptive behavior and overall cognitive abilities. Cognitive skills fell within the severe to profound range of mental deficiency. Differences in cognitive skills according to genetic subtype only partially supported previous research and suggest that there is overlap in abilities across genetic subtypes of AS. Adaptive behavior skills were also significantly delayed, with participants demonstrating a significant strength in socia- lization, and a weakness in motor skills. Strong, positive correlations emerge between cognitive ability scores and adaptive behaviors scores. These results provide further delineation of a cognitive/behavioral phenotype in AS. ß 2004 Wiley-Liss, Inc. KEY WORDS: Angelman syndrome; chromo- some 15; intelligence; adaptive behavior INTRODUCTION Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe mental retardation, ataxia, and a happy/sociable disposition. It is now known that expression of the UBE3A gene from the maternal chromosome is essential to prevent AS [Kishino et al., 1997; Matsuura et al., 1997]. Some descriptive studies have demonstrated slight differ- ences in the functioning of children with AS according to genetic subtype [Lossie et al., 2001]. Specifically, they find that children with the typical deletion have severe to profound mental retardation, are nonverbal, and walk later than children with other genetic subtypes of AS [Lossie et al., 2001]. In addition, some studies have suggested that children with UPD have higher cognitive skills, have a delayed onset of seizures, and have fewer motor difficulties [Bottani et al., 1994; Gillessen-Kaesbach et al., 1995; Fridman et al., 2000]. Other case reports, however, have not found that children with UPD have a ‘‘milder’’ phenotype, and the researchers hypothesize that differences in functioning may be attributable to differ- ences in UBE3A expression from the paternal allele [Smith et al., 1994; Prasad and Wagstaff, 1997]. Despite descriptive data documenting the cognitive and behavioral profiles of children with AS, very few studies have utilized standardized instruments to examine these profiles. One study utilized the Griffiths’ Mental Development Scale (birth–2-year-old version) [Association for Research in Infant and Child Development, 1996], and found that the cognitive abilities of AS children fell between the ages of birth – 2 years, regardless of a child’s chronological age [Andersen et al., 2001]. Adaptive behavior profiles were not explored as part of this study. Virtually no studies have utilized standardized instruments to explore adaptive behavior profiles of children with AS. One formal study evaluating the adaptive behavior profiles of children and adults with AS (age range ¼ 3–52) found that mean adaptive behavior composite scores fell at a 16-month level [Duker et al., 2002]. Relative adaptive strengths and weaknesses were not reported. Reports from case studies and questionnaires note that children with AS can learn to make choices/express preferences, can help with dressing and bathing, and can feed themselves using basic utensils [Clayton-Smith and Laan, 2003]. This study attempts to validate phenotypic descriptions of behavior in AS by using standardized tools to examine the cognitive skills and adaptive behavior of children with AS, patterns of strengths and weaknesses across adaptive behavior domains, and the relationship between adaptive behavior and overall cognitive abilities. It was hypothesized, based on case studies of the cognitive and behavioral profiles of children with AS, that the domain of socialization would be a relative strength, while the domains of motor skills (for children under 6) and communication would be relative weaknesses. METHODS Participants Twenty clinical subjects were brought to the General Clinical Research Center at Texas Children’s Hospital to Grant sponsor: The General Clinical Research Center (to ALB); Grant number: MO1RR00188; Grant sponsor: The Angelman Syndrome Foundation (to ALB); Grant sponsor: The March of Dimes (to CAB); Grant number: 6FY03-73. *Correspondence to: Sarika U. Peters, Department of Pedia- trics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030. E-mail: sarikap@bcm.tmc.edu Received 20 August 2003; Accepted 20 November 2003 DOI 10.1002/ajmg.a.30065 ß 2004 Wiley-Liss, Inc.