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. 2024;97(4):334-342.
doi: 10.1159/000534612. Epub 2023 Oct 16.

Short Stature and Distinct Growth Characteristics in Angelman Syndrome

Noah Gruber  1   2 , Ayman Daka  1   3 , Noy Lapidot  1   3 , Dalit Modan-Moses  1   2 , Orit Pinhas-Hamiel  1   2 , Bruria Ben Zeev  1   4 , Gali Heimer  1   4
Affiliations

Short Stature and Distinct Growth Characteristics in Angelman Syndrome

Noah Gruber et al. Horm Res Paediatr. 2024.

Abstract

Introduction: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: Angelman’s syndrome; Deletion; Growth curves; IGF1; Non-deletion; Short stature.

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Conflict of interest statement

The authors declare to have no conflicts of interest.

Figures

Fig. 1.
Fig. 1.
Height measurements: a Whole cohort males. b Whole cohort females. c Deletion males. d Deletion females. e Non-deletion males. f Non-deletion females plotted on CDC 2000 height charts.
Fig. 2.
Fig. 2.
Comparison between two subgroups through life periods. *Significant difference in height SDS between the two subgroups, p value = 0.03.
Fig. 3.
Fig. 3.
Correlation between height SDS and weight SDS. a All measurements. b Preschool period. c Childhood period. d Height peak velocity period. e Final height period.
Fig. 4.
Fig. 4.
a Correlation between IGF1-SDS and height SDS. b IGF1-SDS change through life periods.
See this image and copyright information in PMC

References

    1. Tan WH, Bacino CA, Skinner SA, Anselm I, Barbieri-Welge R, Bauer-Carlin A, et al. Angelman syndrome: mutations influence features in early childhood. Am J Med Genet A. 2011 Jan;155A(1):81–90. - PMC - PubMed
    1. Lossie AC, Whitney MM, Amidon D, Dong HJ, Chen P, Theriaque D, et al. Distinct phenotypes distinguish the molecular classes of Angelman syndrome [Internet]. Available from: www.jmedgenet.com. - PMC - PubMed
    1. Smith A, Wiles C, Haan E, McGill J, Wallace G, Dixon J, et al. Clinical features in 27 patients with Angelman syndrome resulting from DNA deletion. J Med Genet. 1996;33(2):107–12. - PMC - PubMed
    1. Steffenburg S, Giilberg CL, Steffenburg U, Kyllerman M. Autism in Angelman syndrome: a population-based study. 1996. - PubMed
    1. Williams CA, Beaudet AL, Clayton-Smith J, Knoll JH, Kyllerman M, Laan LA, et al. Angelman syndrome 2005: updated consensus for diagnostic criteria. Am J Med Genet. 2006 Mar 1;140(5):413–8. - PubMed

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