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. 2020 Jan;182(1):53-63.
doi: 10.1002/ajmg.a.61382. Epub 2019 Nov 15.

An overview of health issues and development in a large clinical cohort of children with Angelman syndrome

Karen G C B Bindels-de Heus  1   2 , Sabine E Mous  2   3 , Maartje Ten Hooven-Radstaake  1   2 , Bianca M van Iperen-Kolk  2   4 , Cindy Navis  2   5 , André B Rietman  2   3 , Leontine W Ten Hoopen  2   3 , Alice S Brooks  2   6 ; ENCORE Expertise Center for AS; Ype Elgersma  2   7 , Henriëtte A Moll  1   2 , Marie-Claire Y de Wit  2   8
Affiliations

An overview of health issues and development in a large clinical cohort of children with Angelman syndrome

Karen G C B Bindels-de Heus et al. Am J Med Genet A. 2020 Jan.

Abstract

This study presents a broad overview of health issues and psychomotor development of 100 children with Angelman syndrome (AS), seen at the ENCORE Expertise Center for AS in Rotterdam, the Netherlands. We aimed to further delineate the phenotype of AS, to evaluate the association of the phenotype with genotype and other determinants such as epilepsy and to get insight in possible targets for intervention. We confirmed the presence of a more severe phenotype in the 15q11.2-q13 deletion subtype. Novel findings were an association of (early onset of) epilepsy with a negative effect on development, a high occurrence of nonconvulsive status epilepticus, a high rate of crouch gait in the older children with risk of deterioration of mobility, a relatively low occurrence of microcephaly, a higher mean weight for height in all genetic subtypes with a significant higher mean in the nondeletion children, and a high occurrence of hyperphagia across all genetic subtypes. Natural history data are needed to design future trials. With this large clinical cohort with structured prospective and multidisciplinary follow-up, we provide unbiased data on AS to support further intervention studies to optimize outcome and quality of life of children with AS and their family.

Keywords: UBE3A; development; epilepsy; genotype-phenotype; growth.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Growth parameters. (a) Mean height, (b) Mean weight for height, (c) Mean weight for height deletion versus nondeletion, (d) Mean weight for height UPD‐IC versus UBE3A‐mutation, (e) Mean head circumference at most recent measurement. Dashed line indicates 0 SDS in (a)–(d) and indicates −2 SDS as demarcation of microcephaly in (e). IC, imprinting center defect; UPD, uniparental disomy
Figure 2
Figure 2
Mobility parameters. (a) Mobility score versus genotype, (b) Crouch gait
Figure 3
Figure 3
Developmental parameters. (a) Bayley fine motor raw scores versus age, (b) Bayley gros motor raw scores versus age, (c) Bayley cognitive raw scores versus age, (d) Bayley receptive language raw scores versus age
See this image and copyright information in PMC

References

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