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. Author manuscript; available in PMC: 2013 Nov 24.
Published in final edited form as: Semin Reprod Med. 2012 Apr 27;30(2):10.1055/s-0032-1307417. doi: 10.1055/s-0032-1307417

Table 2.

Studies on Beckwith-Wiedemann Syndrome and Angelman’s Syndrome with Respect to Assisted Reproduction Techniques and Methylation Analysis Imprinting Disorder

Locus and
Genes		 Reference Study
Location		 Study Type Total No. of
Cases in Series		 No. of
Cases and
ART Type		 Cases Studied for Imprinting Expected Etiology
A. Studies published regarding BWS with respect to ART and methylation analysis
BWS 11p15.5
ICF2 and
H19in IC1
(DMR1);
CDKN1C
KCNQ10T1
and KCNQ1 in
IC2 (DMR2)		 1. DeBaun et al, 20035 USA Case series 3/65 (4.6%) BWS cases
had IVF;
4 BWS cases from another
registry (not able to
determine prevalence
of IVF)		 2 IVF/5 ICSI 6 studied;
5 had hypomethylation of IC2;
1 of these had both
hypomethylation of IC2
and hypermethylation
of IC1		 Maternal
hypomethylation
of IC2 (50%);
Maternal gain
methylation
of IC1 (5%);
Paternal UPD (20%);
Mutation of maternal
CDKN1C allele (5%);
Unknown (20%)
Microdeletion (1%);
Translocation/
inversion
(1%);
Duplication (<1%)
2. Maher et al, 20036 UK Case series 6/149 (4%)BWS
cases had IVF		 3 IVF/3 ICSI 4 studied: 0/4 had UPD;
2/4 hypomethylation of IC2
3. Gicquel et al, 20037 France Case series 6/149 (4%) with IVF 4 IVF/2 ICSI 6/6 studied had
hypomethylation of IC2
4. Halliday et al, 20048 Australia Case-control 4/37 (10.8%) of BWS cases
had IVF vs. 1/148
controls had IVF		 3 IVF/1 ICSI 3/3 had hypomethylation
of IC2 (1 BWS in non-IVF was
not studied)
5. Chang et al, 20059 USA Case series 19/341 (5.6%) BWS had
IVF (12 available)		 5 IVF/5 ICSI;
1 CC/IUI; 1 IUI		 ND
6. Rossignol et al, 200610 France Case series 40 BWS with demethylation
of IC2 (11 had IVF
and 29 did not)		 NA 3/11 (27%) IVF and 7/29(24%)
had abnormal methylation at
other loci than IC1 and IC2
7. Sutcliffe et al, 2006120 UK Case series 213 BWS; 83 replied
(4 familial);
11/79(13.9%) had ART		 5 ICSI;
1IVF; 5 OI		 8/8 had hypomethylation of
IC2 (not specified which
had IVForOI)
8. Doornbos 2007143 Dutch Case series 138 BWS; 75 responded and
4/76(1.3%)		 4 IVF;
1 OI; 1 IUI		 6/6 tested had
hypomethylation of IC2
9. Lim 2009144 UK Case series 25 BWS referred compared
with 87 BWS known to
have IC2 hypomethylation		 12 IVF;
13 ICSI		 24/25 had hypomethylation
of IC2;
Loss of maternal allele
methylation in other DMRs
in 37.5% of ART
and 6.4% of non-ART BWS
IC2 defect cases
Total: 656 BWS available Total:
53 (5.9%) IVF		 Total: 46/50 (92%)
Locus and
Genes		 Reference Study
Location		 Study Type Total No. of
Cases in Series		 No. of
Cases and
ART Type		 Cases Studied for Imprinting Expected Etiology
B. Studies published regarding AS with respect to ART and methylation analysis
AS 15q11.2-q13
SNRPN and
UBE3A 		1. Ludwig et al 200513 German Case Series 270 AS requested;
79 replied (30%);
16/79(20.2%)
had infertility		 3 ICSI
5 OI
8 untreated		 1 of 3 hypomethylation
1 of 5 hypomethylation
2 of 8 hypomethylation		 Maternal 6–7Mb
15q11.2-q13
deletion (~68%)
Upd(15)(7%)
IC 6- to 200-kb
deletions (3%)
UBE3A mutations
(11%)
Deletion/ duplication
analysis UBE3A (rare)
2. Sutcliffe et al, 2006120 UK Case series 75 AS cases; 3/75
(4%) had infertility		 2 donor IUI
1 IVF		 2 had deletions
1 had imprinting defect
(donor IUI had
hypomethylation)
3. Doornbos 2007143 Dutch Case series 135 AS cases;
98 responded and
4/98(4.1%) had infertility		 3 OI
1 donor IUI		 2 of 4 had deletion
2 others unknown
23/252 AS patients
(9.1%) had infertility		 4/23 (17.4%)

ART, assisted reproduction techniques; IVF, in vitro fertilization; ICSI, intracytoplasmic sperm injection; OI, ovulation induction; IUI, intrauterine insemination; ND, not determined; NA, not applicable.

Table 2A: Studies 1–5, 7, and 8 were used to calculate frequencies of ART in BWS; study 5 did not examine methylation status (ND = not determined); study 6 could not be used for ART prevalence because it only enrolled 40 BWS patients with hypomethylation of IC2; studies 6 and 9 showed additional loci (other than 11 pi 5.5) that had imprinting abnormalities.