Short Stature and Distinct Growth Characteristics in Angelman Syndrome

Angelman syndrome (AS) is a rare, genetic, neurodevelopmental disorder characterized by severe impairments in speech, cognition, and motor skills accompanied by unique behaviors, distinct facial features, and high prevalence of epilepsy and sleep problems. Despite some reports of short stature among AS patients, this feature 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.

Data were collected from patients' medical files in AS National Clinic. Mutation subtypes were divided to deletion and non-deletion. Four growth periods were defined: preschool, childhood, peak height velocity, and final height.

The cohort included 88 individuals (46 males), with 54 (61.4%) carrying deletion subtype. A median of 3 observations per individual produced 280 data points. Final height SDS was significantly lower compared to general population (-1.23 ± 1.26, p < 0.001), and in deletion group versus non-deletion (-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 general population (-0.55 ± 1.61, p = 0.04), with lower values among deletion group (-0.70 ± 1.44, p = 0.01).

AS patients demonstrate specific growth pattern with deceleration during childhood and adolescence, resulting in significantly decreased final height compared to normal population, and even lower among deletion subgroup, which could be attributed to reduced IGF1 levels. We propose adding short stature to the clinical criteria and developing adjusted growth curves for AS population.