Table 7. [Risks to Sibs of a Proband with Angelman Syndrome by Genetic Mechanism and Parental Genetic Status]. - GeneReviews®

Molecular Class ¹	Families	Genetic Mechanism in Proband	Recommended Parental Testing	Risk to Sibs
Ia	65%-75%	5- to 7-Mb 15q11.2-q13 deletion	Mother: chromosome & FISH analyses	<1% if maternal chromosome & FISH analyses are normal ²
Ib	<1%	Unbalanced chromosome translocation or inherited small interstitial deletion in 15q11.2-q13 region	Mother: chromosome & FISH analyses	<1% if maternal chromosome studies are normal Possibly as high as 50% if the mother has a chromosome rearrangement ³
IIa	3%-7%	Paternal UPD (w/normal karyotype)	Mother & father: chromosome analysis	<1% if both parents have normal chromosome analyses ⁴ (Recurrence risk ≠ 0, as recurrent meiotic nondisjunction of maternal chromosome 15 has been observed. ⁵) Approaches 100% if father has a 15;15 Robertsonian translocation
IIb	<1%	Paternal UPD (w/predisposing parental translocation)
IIIa	0.3%	Imprinting defect w/ deletion in the IC	Mother: targeted testing for the IC deletion (a phenotypically normal mother may have a de novo IC deletion on her paternally derived chromosome 15 or a paternally inherited IC deletion ⁶)	<1% if the IC deletion is not identified in maternal leukocyte DNA ⁶ 50% if the mother is heterozygous for the IC deletion
IIIb	2.5%-3%	Imprinting defect w/o a deletion in the IC		<1% (to date, recurrence of AS in families of probands who have an imprinting defect w/o a deletion in the IC has not been reported) ⁷
IV	11%	UBE3A pathogenic variant	Mother: targeted testing for the UBE3A pathogenic variant	50% if the mother is heterozygous for the UBE3A pathogenic variant (~30% of UBE3A pathogenic variants are inherited.) <1% if the UBE3A pathogenic variant is not identified in maternal leukocyte DNA ⁸
V	10%	"Other" - no identifiable molecular abnormality	NA	Undetermined risk

Molecular Class ¹

Families

Genetic Mechanism in Proband

Recommended Parental Testing

Risk to Sibs

65%-75%

5- to 7-Mb 15q11.2-q13 deletion

Mother: chromosome & FISH analyses

<1% if maternal chromosome & FISH analyses are normal ²

<1%

Unbalanced chromosome translocation or inherited small interstitial deletion in 15q11.2-q13 region

Mother: chromosome & FISH analyses

<1% if maternal chromosome studies are normal
Possibly as high as 50% if the mother has a chromosome rearrangement ³

IIa

3%-7%

Paternal UPD (w/normal karyotype)

Mother & father: chromosome analysis

<1% if both parents have normal chromosome analyses ⁴ (Recurrence risk ≠ 0, as recurrent meiotic nondisjunction of maternal chromosome 15 has been observed. ⁵)
Approaches 100% if father has a 15;15 Robertsonian translocation

IIb

<1%

Paternal UPD (w/predisposing parental translocation)

IIIa

0.3%

Imprinting defect w/ deletion in the IC

Mother: targeted testing for the IC deletion (a phenotypically normal mother may have a de novo IC deletion on her paternally derived chromosome 15 or a paternally inherited IC deletion ⁶)

<1% if the IC deletion is not identified in maternal leukocyte DNA ⁶
50% if the mother is heterozygous for the IC deletion

IIIb

2.5%-3%

Imprinting defect w/o a deletion in the IC

<1% (to date, recurrence of AS in families of probands who have an imprinting defect w/o a deletion in the IC has not been reported) ⁷

11%

UBE3A pathogenic variant

Mother: targeted testing for the UBE3A pathogenic variant

50% if the mother is heterozygous for the UBE3A pathogenic variant (~30% of UBE3A pathogenic variants are inherited.)
<1% if the UBE3A pathogenic variant is not identified in maternal leukocyte DNA ⁸

10%

"Other" - no identifiable molecular abnormality

Undetermined risk

From: Angelman Syndrome

GeneReviews^® [Internet].

Adam MP, Feldman J, Mirzaa GM, et al., editors.

Seattle (WA): University of Washington, Seattle; 1993-2024.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.