■ REVIEW ARTICLE ■ CHROMOSOMAL ABNORMALITIES ASSOCIATED WITH OMPHALOCELE Chih-Ping Chen1,2,3,4* Departments of 1Obstetrics and Gynecology, and 2Medical Research, Mackay Memorial Hospital, Taipei, 3Department of Biotechnology and Bioinformatics, Asia University, Taichung, and 4College of Chinese Medicine, China Medical University, Taichung, Taiwan. SUMMARY Fetuses with omphalocele have an increased risk for chromosomal abnormalities. The risk varies with maternal age, gestational age at diagnosis, association with umbilical cord cysts, complexity of associated anomalies, and the contents of omphalocele. There is considerable evidence that genetics contributes to the etiology of omphalocele. This article provides an overview of chromosomal abnormalities associated with omphalocele and a comprehensive review of associated full aneuploidy such as trisomy 18, trisomy 13, triploidy, trisomy 21, 45,X, 47,XXY, and 47,XXX, partial aneuploidy such as dup(3q), dup(11p), inv(11), dup(1q), del(1q), dup(4q), dup(5p), dup(6q), del(9p), dup(15q), dup(17q), Pallister-Killian syndrome with mosaic tetrasomy 12p and Miller-Dieker lissencephaly syndrome with deletion of 17p13.3, and uniparental disomy (UPD) such as UPD 11 and UPD 14. Omphalocele is a prominent marker for chromosomal abnormalities. Perinatal identification of omphalocele should alert chromosomal abnormalities and familial unbalanced translocations, and prompt thorough cytogenetic investigations and genetic counseling. [Taiwanese J Obstet Gynecol 2007;46(1):1–8] Key Words: chromosomal abnormalities, genetics, omphalocele Introduction Full Aneuploidy Omphalocele has an incidence of 2–3 per 10,000 live Trisomy 18 and trisomy 13 are the most common chro- births and is considered to be a heterogeneous condi- mosomal abnormalities associated with omphalocele tion [1,2]. There is considerable evidence that genetics (Table 1). Snijders et al [4] found omphaloceles in contributes to the etiology of omphalocele and fetuses 22.5% of fetuses with trisomy 18, 9.1% of fetuses with with omphalocele have an increased risk for chromo- trisomy 13, 12.5% of fetuses with triploidy, and 0.045% somal abnormalities. The risk varies with maternal age, of the fetuses without chromosomal abnormalities in gestational age at diagnosis, association with umbilical a first trimester screening study. Snijders et al [4] also cord cysts, complexity of associated anomalies, and the found that the risk for trisomy 18 or trisomy 13 in fetuses contents of omphalocele [3–5]. Chromosomal abnor- with omphalocele at 11–14 gestational weeks was 340 malities have been reported in 10–12% of the neonates times (17% vs. 0.05%) higher than for those without with omphalocele and 30% of the fetuses with omphalo- omphalocele. Chen [11] in a study of 89 consecutive cele [1,4,6–9]. When the diagnosis is made in early cases of fetal trisomy 18 found that 12 cases (13.48%) pregnancy, the percentage of aneuploidy can increase had omphalocele, and the male to female sex ratio in to 61.1–66.7% [8,10]. the fetuses with concomitant omphalocele and trisomy 18 was 2:1. Snijders et al [8] in a study of 18 fetal omphaloce- *Correspondence to: Dr Chih-Ping Chen, Department of Obstetrics les diagnosed at 11–14 gestational weeks found that and Gynecology, Mackay Memorial Hospital, 92, Section 2, 12 cases (66.7%) had chromosomal abnormalities, of Chung-Shan North Road, Taipei 104, Taiwan. E-mail: [email protected] which 10 had trisomy 18, one had trisomy 13, and one Accepted: February 10, 2007 had the karyotype of 69,XXX. Blazer et al [10] in a study Taiwanese J Obstet Gynecol • March 2007 • Vol 46 • No 1 1 C.P. Chen C.P. 2 Table 1. Incidence of chromosomal abnormalities in patients with omphalocele Chromosomal abnormalities Authors Chromosomal Incidence Gestational weeks abnormalities/total at diagnosis* Trisomy Trisomy Trisomy Turner syndrome Triploidy 47,XXX or Others 18 13 21 or 45,X 47,XXY Snijders et al [8] 12/18 66.7% 11–14 10 1 – – – 1 – Blazer et al [10] 11/18 61.1% 12–16 5 1 2 1 2 – – Calzolari et al [2] 94/160 58.8% a 60 23 4 ? ? ? 7 Gilbert and Nicolaides [12] 19/35 54.3% 16–36 (23) 17 – – – 1 1 – Brantberg et al [5] 44/90 48.9% 10–39 (18) 33 5 1 1 2 – 2 van de Geijn et al [13] 10/22 45.5% 12–38 (25) 6 1 – – 1 – 2 Hughes et al [14] 13/30 43.3% 12–40 (21) 4 5 2 1 – – 1 Hwang & Kousseff [15] 37/93 39.8% b 19 2 11 1 – – 4 Nicolaides et al [6] 42/116 36.2% 16–39 (21) 32 6 – – 1 1 2 Goldkrand et al [16] 9/27 33.3% c 531 – – – – Hauge et al [17] 12/40 30% d 822 – – – – Stoll et al [18] 17/58 29.3% e 13 3 1 – – –– Snijders et al [4] 43/153 28.1% 16–26 34 8 – – 1 – – Eydoux et al [19] 12/46 26.1% 15–36 (26) 7 2 – 1 – – 2 Taiwanese JObstetGynecol Taiwanese Hsu et al [20] 6/24 25% f 42– – – – – Getachew et al [3] 5/22 22.7% 15–34 (24) 3 1 – – – – 1 De Veciana et al [21] 9/40 22.5% 12–39 (21) 5 3 – – – 1 – Benacerraf et al [22] 4/22 18.2% 14–28 1 2 – – 1 – – Chen et al [23] 4/25 16% 14–38 (26) 3 1 – – – –– Salihu et al [24] 3/26 11.5% c 21– – – – – St-Vil et al [9] 9/83 10.8% g 6–2 1 – – – • March 2007 *Mean gestational age shown in parentheses; aThe surveyed population included livebirths, stillbirths, and induced abortions following prenatal diagnosis; bNinety-three karyotyped cases were among 127 cases of omphalocele (74 prenatal cases and 53 pediatric cases); cAll cases were detected prenatally by ultrasound; dThirty-seven live cases and three stillbirths; eDiagnosis was performed prenatally in 61.9% of the cases and the others were diagnosed at birth or in the 1st week of life; fTwenty-four karyotyped cases were among 50 infants with omphalocele and an average gestational age of 38.5 weeks at birth; gFifty prenatal cases and 33 pediatric cases. • Vol 46 Vol • No 1 Omphalocele of 18 fetal omphaloceles diagnosed at 12–16 gesta- trisomy 13, and one had trisomy 21. Hauge et al [17] tional weeks found that 11 cases (61.1%) had chromo- in a study of 40 cases of omphaloceles found that 12 somal abnormalities, of which five had trisomy 18, two cases (30%) had chromosomal abnormalities, of which had trisomy 21, two had triploidy, one had trisomy 13, eight had trisomy 18, two had trisomy 13, and two and one had the karyotype of 45,X. Calzolari et al [2] had trisomy 21. Stoll et al [18] in a study of 58 births in a study of 160 cases of omphaloceles in 21 regional with omphaloceles found that 17 cases (29.3%) had registers in Europe (EUROCAT registers) found that 94 chromosomal abnormalities, of which 13 had trisomy cases (58.8%) had chromosomal abnormalities, of which 18, three had trisomy 13, and one had trisomy 21. 60 had trisomy 18, 23 had trisomy 13, four had trisomy Snijders et al [4] in a study of 153 fetal omphaloceles 21, and seven had other chromosomal abnormalities. found that 43 cases (28.1%) had chromosomal abnor- Gilbert and Nicolaides [12] in a study of 35 fetal malities, of which 34 had trisomy 18, eight had trisomy omphaloceles found that 19 cases (54.3%) had chro- 13, and one had triploidy. Eydoux et al [19] in a study mosomal abnormalities, of which 17 had trisomy 18, of 46 fetal omphaloceles found that 12 cases (26.1%) one had triploidy, and one had the karyotype of 47,XXY. had chromosomal abnormalities, of which seven had The male to female sex ratio was 3:1. Brantberg et al trisomy 18, two had trisomy 13, one had the karyotype [5] in a study of 90 prenatally diagnosed omphaloceles of 45,X, one had i(18q), and one had a balanced found that 44 cases (48.9%) had chromosomal abnor- translocation of t(9;11)(p13;q13). Hsu et al [20] in a malities, of which 33 had trisomy 18, five had trisomy study of 24 infants with omphaloceles found that six 13, two had triploidy, one had trisomy 21, one had cases (25%) had chromosomal abnormalities, of which Turner syndrome, one had the karyotype of mos 47,XY, + four had trisomy 18 and two had trisomy 13. Getachew 18/92,XXXY, and one had the karyotype of 47,XY, + et al [3] in a study of 22 fetal omphaloceles found that der(13)t(3;13)(q29;q21.2)mat. The male to female five cases (22.7%) had chromosomal abnormalities, of ratio was 1.9:1. The sex ratio was 2.1:1 for central which three had trisomy 18, one had trisomy 13, and omphalocele and 1.6:1 for epigastric omphalocele. Of one had inv(11). De Veciana et al [21] in a study of interest is that chromosomal abnormalities were found 40 fetal omphaloceles found that nine cases (22.5%) in 40/58 (69%) of the fetuses with central omphalocele had chromosomal abnormalities, of which five had tri- and in 4/32 (12.5%) of the fetuses with epigastric somy 18, three had trisomy 13, and one had the kary- omphalocele. van de Geijn et al [13] in a study of 22 otype of 47,XXX. Benacerraf et al [22] in a study of 22 fetal omphaloceles found that 10 cases (45.5%) had fetal omphaloceles found that four cases (18.2%) had chromosomal abnormalities, of which six had trisomy chromosomal abnormalities, of which one had trisomy 18, one had trisomy 13, one had triploidy, one had 18, two had trisomy 13, and one had triploidy.