Phenotypic and behavioral variability within Angelman Syndrome group with UPD

Abstract

The Angelman syndrome (AS) (developmental delay, mental retardation, speech impairment, ataxia, outbursts of laughter, seizures) can result either from a 15q11-q13 deletion, or from paternal uniparental disomy (UPD), imprinting, or UBE3A mutations. We describe here the phenotypic and behavioral variability detected in eight UPD patients out of a group of 58 AS patients studied. All of them presented developmental delay, mental retardation, ataxia, speech impairment, and frequent drooling. Only one had microcephaly, whereas in two of them the OFC (head circumference) was above the 98 th percentile. The weight of all patients was above the 50 th percentile, and in three of them the height was above the 90 th percentile. Three were able to say a few words and to communicate by gestures. Two patients presented hyperphagia, and three presented skin picking, common features in the Prader-Willi syndrome (PWS). Four patients (4/7) had wide-spaced teeth. Five presented seizures, and two others did not manifest frequent laughter. One patient was very different from the others, as he showed a better understanding and abilities to communicate, to play video games and to draw. We suggest here that there seems to be an extreme phenotypic and behavioral variability within the UPD group, and that both typical patients and those with mental retardation, language impairment, happy disposition, and hyperactivity should be tested for AS.

Phenotypic variability in Angelman syndrome: comparison among different deletion classes and between deletion and UPD subjects

“…In AS, most paternal UPD15 seem to be postzygotic events. 24,18 In the present study, in addition to the differences described previously, 13 deletion patients presented a higher incidence of swallowing disorders (73.9 Â 22.2%) and hypotonia (73.3 Â 28.57%) than UPD patients. Other features associated with the clinical diagnosis of AS, such as brachycephaly, occipital groove, macrostomia, wide-spaced teeth, outbursts of laughter, hyperactivity, sleep disturbance and frequent drooling, presented a higher incidence among deletion patients, suggesting that these patients have a more severe and more typical phenotype, although these differences did not reach statistical significance (Table 2).…”

Nutritional Phases in Prader-Willi Syndrome: Evolutionary and Clinical Interpretations

“…Clarification of symptomatic differences between these two descriptors would help further evolutionary understanding. Observations that some individuals with AS develop hyperphagia [29,30,31,32] and that a few males with PWS develop anorexia nervosa [33,34] add further complications. Clearly, there is much still to be learned about the natural history of appetite and food-related behaviors in PWS and AS.…”

Case Report: An Atypical Angelman Syndrome Case With Obesity and Fulfilled Autism Spectrum Disorder Identified by Microarray

“…These UPD children also had significantly higher birth weight than children with deletions or UBE3A mutations ( Mertz et al, 2014 ). AS patients caused by UPD with no ataxia ( Poyatos et al, 2002 ; Saitoh et al, 2005 ; Horváth et al, 2013 ; Luk and Lo, 2016 ) or no happy demeanor ( Fridman et al, 2002 ; Varela et al, 2004 ; Bonati et al, 2007 ; Depienne et al, 2009 ; Luk and Lo, 2016 ) have also been reported. Moreover, it is notable that, despite one earlier study suggesting a decreased risk of ASD in AS in the absence of seizure ( Thompson and Bolton, 2003 ), our case presented with autistic features without any history of seizure.…”