Line Granild Bie Mertz1, Rikke Christensen2, Ida Vogel2, Jens Michael Hertz3, John R Østergaard4. 1. Centre for Rare Diseases, Department of Pediatrics, Aarhus University Hospital, Denmark. Electronic address: linebiemertz@dadlnet.dk. 2. Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark. 3. Department of Clinical Genetics, Odense University Hospital, Odense, Denmark. 4. Centre for Rare Diseases, Department of Pediatrics, Aarhus University Hospital, Denmark.
Abstract
BACKGROUND: Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability, epilepsy, and low threshold for laughter. AIMS: We investigated the occurrence and severity of epilepsy and laughter-induced loss of postural muscle tone determined by the different genetic subtypes. METHODS: This study included 39 children with AS. Deletion breakpoints were determined by high resolution CGH microarray (1×1M Agilent). Clinical data were based on a parent interview and medical record review. RESULTS: All patients with AS based on a deletion had epilepsy. Epilepsy was present in 3/4 children with UBE3A mutation, and 4/5 with pUPD. Onset of epilepsy occurred earlier in deletion cases compared to pUPD or UBE3A mutations cases. Laughter-induced postural muscle tone loss occurred only among deletion cases. We found no differences in severity of epilepsy between children with a larger Class I or a smaller Class II deletions, or between the total group with a deletion compared to children with pUPD or a UBE3A mutation. The drugs most frequently prescribed were benzodiazepines in monotherapy, or a combination of benzodiazepines and valproic acid. CONCLUSION: Epilepsy is very common in patients with AS, especially in patients with a deletion. Postural muscle tone loss and collapsing during outbursts of laughter were seen in patients with a deletion only.
BACKGROUND:Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability, epilepsy, and low threshold for laughter. AIMS: We investigated the occurrence and severity of epilepsy and laughter-induced loss of postural muscle tone determined by the different genetic subtypes. METHODS: This study included 39 children with AS. Deletion breakpoints were determined by high resolution CGH microarray (1×1M Agilent). Clinical data were based on a parent interview and medical record review. RESULTS: All patients with AS based on a deletion had epilepsy. Epilepsy was present in 3/4 children with UBE3A mutation, and 4/5 with pUPD. Onset of epilepsy occurred earlier in deletion cases compared to pUPD or UBE3A mutations cases. Laughter-induced postural muscle tone loss occurred only among deletion cases. We found no differences in severity of epilepsy between children with a larger Class I or a smaller Class II deletions, or between the total group with a deletion compared to children with pUPD or a UBE3A mutation. The drugs most frequently prescribed were benzodiazepines in monotherapy, or a combination of benzodiazepines and valproic acid. CONCLUSION:Epilepsy is very common in patients with AS, especially in patients with a deletion. Postural muscle tone loss and collapsing during outbursts of laughter were seen in patients with a deletion only.
Authors: Karen G C B Bindels-de Heus; Sabine E Mous; Maartje Ten Hooven-Radstaake; Bianca M van Iperen-Kolk; Cindy Navis; André B Rietman; Leontine W Ten Hoopen; Alice S Brooks; Ype Elgersma; Henriëtte A Moll; Marie-Claire Y de Wit Journal: Am J Med Genet A Date: 2019-11-15 Impact factor: 2.802