Angelman and Prader‐Willi syndrome: A magnetic resonance imaging study of differences in cerebral structure

Abstract

Recent improvements in magnetic resonance imaging techniques now allow the developing brain to be visualized in sufficient detail to perform "in vivo neuropathology." In this study we compared the cortical morphology in six children with Angelman and four with Prader-Willi syndrome. These two syndromes are of special interest because, although they are both caused by deletions in the same region of chromosome 15, Angelman children are far more severely affected, and do not speak. We measured the length of the banks of the Sylvian fissure in a gapless series of thin sagittal images. Angelman children had a significantly larger proportion (75%) of anomalous fissures than the Prader-Willi children (12%). Anomalous cortical growth could result from mistimed expression and recognition of macromolecules involved in axonal guidance, target recognition, and pruning. We hypothesize that misrouting of long projection axons may be related to the Sylvian fissure anomalies and the language disorder in Angelman syndrome.

Sylvian fissure morphology in Prader-Willi syndrome and early-onset morbid obesity

“…34 In light of the prevalence of speech and language disorders in individuals with PWS, 9,35 as well as an indication of decreased asymmetry reported earlier, 10 we expected to find decreased asymmetry again. In contrast, the larger group of PWS-D had a normal pattern of planum temporale asymmetry.…”

“…One study, using magnetic resonance imaging (MRI), reported a lack of normal sylvian fissure asymmetry in four individuals with PWS. 10 A previous qualitative study from our group identified multiple brain abnormalities in individuals with PWS, including ventriculomegaly, sylvian fissure polymicrogyria, and incomplete sylvian fissure/ insula closure. 11 Although no abnormalities were seen in a comparison group of individuals with early-onset morbid obesity (EMO) of unknown etiology, we did note similarities between individuals with PWS and those with EMO on cognitive and achievement testing using the Woodcock-Johnson Tests of Cognitive Abilities and Achievement, Third Edition (WJ-III).…”

“…22,23 Although the clinical significance of these asymmetries is controversial, 24 a previous study found a lack of this asymmetry in four individuals with PWS, suggesting that some of the speech and language abnormalities in this syndrome may be associated with structural brain differences. 10 Sylvian fissure morphology has been classified by a system developed by Steinmetz et al 25 Long fissures (type 2/3), associated with multiple gyri in the operculum, are more common on the left, whereas short fissures (type 4), associated with missing gyri, are more common on the right. 25 Given the indications of sylvian fissure/insula abnormalities in PWS, we aimed to characterize fissure morphology within our sample of individuals with PWS and EMO and compare the prevalence of various fissure types with a previously recorded distribution in a normal population.…”

“…25 The primary aims of the current study were to (1) establish whether quantitative measurements of insula closure verified our qualitative findings that individuals with PWS have incomplete insula closure 12 ; (2) investigate whether the proportion of nontypical sylvian fissure types differ in PWS, EMO, and controls as would be predicted by the speech and language problems exhibited in individuals with PWS and EMO; and (3) determine whether individuals with PWS have diminished planar asymmetry, confirming findings from the small sample studied previously. 10 …”

Epigenetics of Complex Diseases: From General Theory to Laboratory Experiments

“…Such epigenetic events result in known aberrations of brain development. For example, Angelman syndrome-which presents with paroxysms of laughter, seizures, attention deficit, hyperactivity and aggressive behaviour-frequently shows anomalous cortical growth, resulting in cortical atrophy, microencephaly and ventricular dilation (Leonard et al 1993;Schumacher 2001;Williams et al 1989). …”