Angelman syndrome in adulthood

Abstract

Angelman syndrome (AS) is a neurogenetic disorder. The goal of this study was to investigate the primary health issues affecting adults with AS and to further characterize the natural history and genotype-phenotype correlations. Standardized phone interviews with caregivers for 110 adolescents and adults with AS were conducted. The impact of age, gender, and genotype on specific outcomes in neurology, orthopedics, internal medicine, and psychiatry were investigated. The mean age of individuals with AS was 24 years (range 16–50y). Active seizures were present in 41% of individuals, and 72% had sleep dysfunction. Significant constipation was present in 85%, and 32% were overweight or obese, with obesity disproportionately affecting women. Scoliosis affected 50% with a mean age at diagnosis of 12 years, and 24% of those diagnosed with scoliosis required surgery, an intervention disproportionately affecting men. Sixty-eight percent were able to walk independently, and 13% were able to speak 5 or more words. Self-injurious behavior was exhibited in 52% of individuals. The results of this study indicate that epilepsy severity may assume a bimodal age distribution: seizures are typically most severe in early childhood but may recur in adulthood. While late-adolescent and adult sleep patterns were improved when compared to the degree of sleep dysfunction present during infancy and childhood, the prevalence of poor sleep in adults remained quite high. Primary areas of clinical management identified include the following: seizures, sleep, aspiration risk, GERD, constipation, dental care, vision, obesity, scoliosis, bone density, mobility, communication, behavior, and anxiety.

Persistent neuronal Ube3a expression in the suprachiasmatic nucleus of Angelman syndrome model mice

“…Sleep disturbances in individuals with AS persist throughout childhood and manifest as reduced need for sleep, difficulties falling asleep, and sleep fragmentation111213. Sleep disturbances in AS model mice ( Ube3a m –/ p + ), in which a null allele of Ube3a is maternally inherited, have also been consistently observed1415.…”

Anxiety‐associated and separation distress‐associated behaviours in Angelman syndrome

“…However, to date, only three studies have explicitly described anxiety in AS (Larson et al . ; Wink et al . ; Prasad et al .…”

“…Results of these studies suggest that, when asked in an interview, nearly half of caregivers report high anxiety in their family member with AS (Larson et al . ), with these numbers increasing significantly in individuals over 26 years of age (Prasad et al . ).…”

“…Anxiety is listed as a 'frequent' feature in the consensus reports (Williams et al 2006), and studies of stress and anxiety in the AS mouse model suggest that increased anxiety-like behaviour may be directly associated with loss of UBE3A (Godavarthi et al 2012). However, to date, only three studies have explicitly described anxiety in AS (Larson et al 2015;Wink et al 2015;Prasad et al 2018). Results of these studies suggest that, when asked in an interview, nearly half of caregivers report high anxiety in their family member with AS (Larson et al 2015), with these numbers increasing significantly in individuals over 26 years of age (Prasad et al 2018).…”

“…However, to date, only three studies have explicitly described anxiety in AS (Larson et al 2015;Wink et al 2015;Prasad et al 2018). Results of these studies suggest that, when asked in an interview, nearly half of caregivers report high anxiety in their family member with AS (Larson et al 2015), with these numbers increasing significantly in individuals over 26 years of age (Prasad et al 2018). However, on standardised measures of anxiety, individuals with AS were not rated as having diagnostically elevated social avoidance, generalised anxiety or obsessivecompulsive behaviour (Wink et al 2015).…”