ESPE Abstracts

Objectives: Angelman syndrome (AS) is a rare, genetic, neurodevelopmental disorder characterized by developmental delay with severe impairments in speech, motor and coordination dysfunction and unique behaviors, accompanied with distinct facial features and high prevalence of epilepsy and sleep problems. Despite few reports regarding short stature among AS patients, this feature has not been extensively studied and is not included in the clinical criteria defined in 2005. We investigated growth patterns among AS patients with respect to mutation type, growth periods, family history and endocrine abnormalities.

Methods: Data regarding growth and puberty of patients and their parents were collected from medical files of AS patients in the national AS clinic. The cohort was divided into two subgroups – deletion and non-deletion. Growth data was divided to four main periods – preschool, childhood, peak height velocity and final height.

Results: The cohort included 88 individuals (46 males), out of which 54 (61.4%) had the deletion subtype. There was a median of 3 observations per individual (range 1-10), which produced 280 data points distributed from birth to final height. Mean final height-SDS of the cohort was significantly lower compared to the general population (-1.23 ±1.26, P<0.001), and among the deletion subgroup it was significantly lower compared to the non-deletion subgroup (-1.67±1.3 vs -0.65±0.96, P=0.03). Final height-SDS was significantly lower compared to height SDS in preschool period (-1.32 vs -0.47, P=0.007). Patient's final-height-SDS was significantly lower than the parents' (∆final-height-SDS=0.94±0.99, P=0.002). IGF1-SDS was significantly decreased compared to the general population (-0.55±1.61, P=0.04), with lower values among the deletion group (-0.70±1.44, P=0.01). IGF1 was positively correlated with height-SDS (r=0.65, P=0.007). No significant changes were seen in timing of puberty.

Conclusions: AS patients demonstrate a unique growth pattern, with deceleration throughout life up to a significantly decrease in final height compared to the normal population, and even lower among the deletion subgroup, which could be attributed to decreased IGF1 levels. We propose to add short stature to the clinical criteria and develop adjusted growth curves for the AS population.

Key word: Angelman syndrome, growth curves, short stature, height, weight, deletion, non-deletion, IGF1.