Bone health in children with Angelman Syndrome at the ENCORE Expertise Center

Abstract

Abstract Purpose Angelman Syndrome (AS) is a rare genetic disorder due to lack of UBE3A function on chromosome 15q11.2q13 caused by a deletion, uniparental paternal disomy (UPD), imprinting center disorder (ICD) or pathological variant of the UBE3A gene. AS is characterized by developmental delay, epilepsy, and lack of speech. Although fractures are reported frequently in clinical practice, there are few studies on bone health in AS. The aim of this study is to investigate bone health in children with AS. Methods Prospective cohort study of 91 children with AS visiting the ENCORE Expertise Center for AS between April 2010 and December 2021. Bone health was assessed with the Bone Health Index (BHI) in standard deviation score (SDS) measured by digital radiogrammetry of the left hand using BoneXpert software. Risk factors analyzed were age, sex, genetic subtype, epilepsy, anti-seizure medication (ASM) use, mobility, BMI, and onset of puberty. Results Children with AS had a mean BHI of -1.77 SDS (SD 1.4). A significantly lower BHI was found in children with a deletion (-2.24 SDS) versus non-deletion (-1.02 SDS). Other factors associated with reduced BHI-SDS were inability to walk and late onset of puberty. Children with a history of one or more fractures (22%) had a significantly lower BHI than children without fractures (-2.60 vs -1.56 SDS). Longitudinal analysis showed a significant decrease in BHI-SDS with age in all genetic subtypes. Conclusions Children with AS have a reduced bone health. Risk factors are deletion genotype, no independent walking, and late onset of puberty. Bone health decreased significantly with age.