gumangenetik 26, 113--116 (1975) © by Springer-Verlag 1975 Kurze
Originalmitteilungen Communications
• Short
Communications
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Prevalence of Edwards' Syndrome. Clustering and Seasonal Variation? J o h a n n e s Nielsen The Cytogenetic Laboratory, Arhus State HHospitM,Risskov, Denmark Vagn Holm The Pediatric Department, Centralsygehuset, Herning, Denmark
Jorgen Haahr The Pediatric Department, Centralsygehuset, Viborg, Denmark Received August 22, 1974 Summary. The incidence of Edwards' syndrome was found to be 1 per 4857 newborn children of 34000 consecutively newborn children in two Danish counties. Six of the 7 cases were born during the months of February through April. The incidence was high compared with the expected incidence of Edwards' syndrome of approximately 1 per 10000. This might be due to clustering in the area studied during the period 1967 to 1973. The finding of variations in incidence of children with Edwards' syndrome in different parts of the world, as well as the finding of seasonal variation in birth of such children, indicates that some of the etiological factors of nondisjunction of chromosome 18 are of an environmental nature.
Prevalence and C|ustering of Edwards' Syndrome W e h a v e m a d e c h r o m o s o m e e x a m i n a t i o n of all children referred from one D a n i s h p e d i a t r i c d e p a r t m e n t (Herning) d u r i n g a 7-year period a n d from a n o t h e r (Viborg) d u r i n g a 1 ~ - y e a r period. The n u m b e r of l i v e b o r n children in t h e receiving areas for these t w o d e p a r t m e n t s d u r i n g t h e p e r i o d of i n v e s t i g a t i o n was app r o x i m a t e l y 34000. W e found 7 eases of t r i s o m y 18 ( E d w a r d s ' syndrome) d u r i n g this period, i.e. 1 per 4857 children. This is a higher f r e q u e n c y t h a n t h e 1 p e r 10 750 f o u n d a m o n g 43 558 children, all of w h o m h a d a chromosome e x a m i n a t i o n m a d e in 6 different studies as shown in T a b l e 1, t h e 1 p e r i1 163 children f o u n d b y Conen a n d E r k m a n (1966), a n d t h e 1 per 8119 children f o u n d b y T a y l o r a n d R o b e r t s (1968). I t is, however, v e r y similar to t h e 1 per 3000 children f o u n d in t h e pooled studies b y H e c h t et al. (1963), S m i t h (1964) a n d T a y l o r a n d Moores (1967). Our findings of one child w i t h E d w a r d s ' s y n d r o m e a m o n g 4857 is, however, a m i n i m u m figure, as some children w i t h this chromosome a b e r r a t i o n in t h e receiving areas o f t h e two p e d i a t r i c d e p a r t m e n t s m o s t p r o b a b l y died before t h e y could be referred to t h e p e d i a t r i c d e p a r t m e n t s , a n d some were p r o b a b l y n o t referred. Our group is t o o small to s t u d y t h e p o s s i b i l i t y of clustering, b u t t h e reason for t h e high f r e q u e n c y m i g h t a c t u a l l y be a clustering of eases during t h e y e a r s
114
J. Nielsen et al.
of the study. Clustering of birth of children with E d w a r d s ' s y n d r o m e has previously been reported b y Heinrichs et al. (1963), Conen a n d E r k m a n (1966) a n d T a y l o r (1968). Seasonal Variation in Birth of Children with Edwards' Syndrome I t was remarkable t h a t 6 of the 7 cases were b o r n during the m o n t h s of F e b r u a r y to April with the a n t i c i p a t e d m o n t h s of conception from May to J u l y , considering t h a t there is a r a n d o m seasonal d i s t r i b u t i o n of childbirths in D e n m a r k
Table 1. Edwards' syndrome among newborn children Authors
Number of newborns ascertained
Number of children with Edwards' syndrome
Hecht et al. (1963) Smith (1964) Taylor and Moores (1967) Conen and Erkman (1966) Taylor and Fraser (1968) Jacobs et al. (1974)a Present study
999 10345 9 688 198599 94 000 43558 34000
2 ] 3 / 7 2 16 11 4 7
Rate
1/3000 1/12412 1/8119 1/10750 1/4857
a Studies of consecutive newborn children as recently surveyed by Jaeobs et al. (t974), Edinburgh (Friedrieh and Nielsen (1973) from Denmark; Sergovich et al. (1969) from Ontario, Canada; Hamerton et al. (1972) from Winnipeg, Canada; Walzer and Gerald (1970) from Boston, USA; Lubs and Ruddle (1970) from New ]-Iaven, USA, and Jacobs et al. (1974) from Edinburgh). In the other studies chromosome examination was only made of those children who had signs of chromosome abnormalities. Table 2. Seasonal variation in birth of patients with Edwards' syndrome Month of conception
Month of birth
Patients with Edwards' syndrome Canada England Denmark 1961--1965 1962--1967 1967--1973
10 11 12 i 2 3 4 5 6 7 8 9
1 2 3 4 5 6 7 8 9 10 11 12
3 1 4 2 3 2 ---1 ---
Total
16
-/
2 1
94%
1
22%
2
6%
5 4 2 4 3 3 27
1 3 2 [ 86°/o
-/I 78%
-- ~ 14% 1
/
7
Canada: Conen and Erkman (1966); England: Taylor (1968); Denmark: Present study.
Prevalence of Edwards' Syndrome
115
Table 3. Patients with karyotypes 47,XX¥, 47,XY¥, 47,XXX and 45,X. Distribution by month of birth and month of conception Month of birth Oct.
Total
Nov, Dee.
Jan.
Febr. March April May
June July
Aug. Sept.
Aug. Sept. Oct.
Nov. Dec.
Month of conception Jan. Observed Expected X2
Febr. YfarchApril May
June July
27 19 21 22 25 37 38 37 10 18 25 18 23.49 22.60 23.42 24.48 24.14 27.62 26.70 26.52 24.56 24.76 24.51 24.22
297 297.02
0.524 0.573 0.250 0.251 0.031 3.186 4.7~2 4.141 8.632 1.846 0.010 1.597
Z~, 11 df = 25.824
25.8.24
0.005 < P < 0.01
The expected rates are calculated on all live-born children in Denmark during the range of years of birth for the 297 patients with aneuploid sex chromosome abnormalities, i.e. 1896--1970. 47,XXY (n = 1 8 4 ) 47,XYY (n = 28) 47,XXX (n = 7) 45,X (n -~ 78)
45 40
"~°
Observed
{ n - 297)
35 "~
3o
®
25
m
t-]/\i
20 ¢.
¢
]5 Io
'I 1o
'2 11
13 12
4. . .5 . . 6 . 1 2 3
7 4
8 5
9 6
Io' 7
1'1 8
I '2 9
I~onth of conception Honth of birth
Fig. 1 Patients with karyotypes 47,XXY, 47,XYY, 47,XXX and 45,X. Distribution by month of birth and month of conception
as shown in t h e s t u d y b y Nielsen et al. (1973) a n d in Table 3. The t i m e of increase in conception of children w i t h E d w a r d s ' s y n d r o m e in our s t u d y , as well as in t h e s t u d y b y Cohen a n d E r k m a n from C a n a d a is M a y to J u l y a n d correlates with t h e finding of a significant seasonal v a r i a t i o n in conception of children with sex c h r o m o s o m e a b e r r a t i o n s registered in t h e Danish Cytogenetic Central l~egister as seen in Fig. 1 a n d T a b l e 3. T a b l e 2 shows t h e correlation b e t w e e n a s t u d y from C a n a d a a n d t h e p r e s e n t s t u d y of a significant increase in f r e q u e n c y of b i r t h of p a t i e n t s with E d w a r d s ' s y n d r o m e from J a n u a r y to June. The s t u d y b y T a y l o r from E n g l a n d of 27 cases with E d w a r d s ' s3mdrome shows quite t h e opposite with 78% of t h e p a t i e n t s
116
J. Nielsen et al.
with E d w a r d s ' s y n d r o m e born during t h e m o n t h s J u l y till D e c e m b e r as seen in Table 1. The v a r i a t i o n in f r e q u e n c y of t r i s o m y 18 in t h e studies from different p a r t s of t h e world, t h e seasonal v a r i a t i o n in b i r t h of children w i t h t r i s o m y 18, a n d clustering i n d i c a t e t h a t t h e r e are some e n v i r o n m e n t a l factors a m o n g t h e etiological factors of n o n d i s j u n c t i o n of chromosome 18 as p r e v i o u s l y f o u n d for nondisjunction of sex chromosomes. Comparison of clustering a n d seasonal v a r i a t i o n in b i r t h of children w i t h E d w a r d s ' s y n d r o m e in different p a r t s of t h e world should be m a d e in order to look for possible e n v i r o n m e n t a l etiological factors.
References Cohen, P. E., Erkman, B.: Frequency and occurrence of chromosomal syndromes II. Etrisomy. Amer. J. hum. Genet. 18, 387--398 (1966) Hecht, F., Motulsky, A. G., Gilbertt, E. R.: The no. 17--18 (E) trisomy syndrome. Studies on cytogenetics, dermatoglyphics, paternal age and linkage. J. Pediat. 63, 605 (1963) Heinrichs, E. H., Allen, S. W., Nelson, P. S. : Simultaneous 18-trisomy and 21-trisomy cluster. Lancet 1968 II, 468 Nielsen, J., Petersen, G. B., Therkelsen, A. J. : Seasonal variation in the birth of children with aneuploid chromosome abnormalities. Humangenetik 19, 67--74 (1973) Smith, D. W. : Autosomal abnormalities. Amer. J. Obstet. Gynec. 90, 1055 (1964) Taylor, A. I , Moores, E. C. : A sex chromatin survey of newborn children in two London hospitals. J. reed. Genet. 4, 258 (1967) Taylor, A. I. : Autosomal trisomy syndromes: A detailed study of 27 cases of Edwards' syndrome and 27 cases of Patau's syndrome. J. med. Genet. 5, 227--252 (1968) Taylor, A. I., t~oberts, J. F. (quoted as unpublished by Taylor, A. I.) in J. reed. Genet. 5, 227--252 (1968) Dr. J. Nielsen The Cytogenetic Laboratory Arhus State Hospital l~isskov, Denmark
Originalmitteilungen Communications
• Short
Communications
brOves
Prevalence of Edwards' Syndrome. Clustering and Seasonal Variation? J o h a n n e s Nielsen The Cytogenetic Laboratory, Arhus State HHospitM,Risskov, Denmark Vagn Holm The Pediatric Department, Centralsygehuset, Herning, Denmark
Jorgen Haahr The Pediatric Department, Centralsygehuset, Viborg, Denmark Received August 22, 1974 Summary. The incidence of Edwards' syndrome was found to be 1 per 4857 newborn children of 34000 consecutively newborn children in two Danish counties. Six of the 7 cases were born during the months of February through April. The incidence was high compared with the expected incidence of Edwards' syndrome of approximately 1 per 10000. This might be due to clustering in the area studied during the period 1967 to 1973. The finding of variations in incidence of children with Edwards' syndrome in different parts of the world, as well as the finding of seasonal variation in birth of such children, indicates that some of the etiological factors of nondisjunction of chromosome 18 are of an environmental nature.
Prevalence and C|ustering of Edwards' Syndrome W e h a v e m a d e c h r o m o s o m e e x a m i n a t i o n of all children referred from one D a n i s h p e d i a t r i c d e p a r t m e n t (Herning) d u r i n g a 7-year period a n d from a n o t h e r (Viborg) d u r i n g a 1 ~ - y e a r period. The n u m b e r of l i v e b o r n children in t h e receiving areas for these t w o d e p a r t m e n t s d u r i n g t h e p e r i o d of i n v e s t i g a t i o n was app r o x i m a t e l y 34000. W e found 7 eases of t r i s o m y 18 ( E d w a r d s ' syndrome) d u r i n g this period, i.e. 1 per 4857 children. This is a higher f r e q u e n c y t h a n t h e 1 p e r 10 750 f o u n d a m o n g 43 558 children, all of w h o m h a d a chromosome e x a m i n a t i o n m a d e in 6 different studies as shown in T a b l e 1, t h e 1 p e r i1 163 children f o u n d b y Conen a n d E r k m a n (1966), a n d t h e 1 per 8119 children f o u n d b y T a y l o r a n d R o b e r t s (1968). I t is, however, v e r y similar to t h e 1 per 3000 children f o u n d in t h e pooled studies b y H e c h t et al. (1963), S m i t h (1964) a n d T a y l o r a n d Moores (1967). Our findings of one child w i t h E d w a r d s ' s y n d r o m e a m o n g 4857 is, however, a m i n i m u m figure, as some children w i t h this chromosome a b e r r a t i o n in t h e receiving areas o f t h e two p e d i a t r i c d e p a r t m e n t s m o s t p r o b a b l y died before t h e y could be referred to t h e p e d i a t r i c d e p a r t m e n t s , a n d some were p r o b a b l y n o t referred. Our group is t o o small to s t u d y t h e p o s s i b i l i t y of clustering, b u t t h e reason for t h e high f r e q u e n c y m i g h t a c t u a l l y be a clustering of eases during t h e y e a r s
114
J. Nielsen et al.
of the study. Clustering of birth of children with E d w a r d s ' s y n d r o m e has previously been reported b y Heinrichs et al. (1963), Conen a n d E r k m a n (1966) a n d T a y l o r (1968). Seasonal Variation in Birth of Children with Edwards' Syndrome I t was remarkable t h a t 6 of the 7 cases were b o r n during the m o n t h s of F e b r u a r y to April with the a n t i c i p a t e d m o n t h s of conception from May to J u l y , considering t h a t there is a r a n d o m seasonal d i s t r i b u t i o n of childbirths in D e n m a r k
Table 1. Edwards' syndrome among newborn children Authors
Number of newborns ascertained
Number of children with Edwards' syndrome
Hecht et al. (1963) Smith (1964) Taylor and Moores (1967) Conen and Erkman (1966) Taylor and Fraser (1968) Jacobs et al. (1974)a Present study
999 10345 9 688 198599 94 000 43558 34000
2 ] 3 / 7 2 16 11 4 7
Rate
1/3000 1/12412 1/8119 1/10750 1/4857
a Studies of consecutive newborn children as recently surveyed by Jaeobs et al. (t974), Edinburgh (Friedrieh and Nielsen (1973) from Denmark; Sergovich et al. (1969) from Ontario, Canada; Hamerton et al. (1972) from Winnipeg, Canada; Walzer and Gerald (1970) from Boston, USA; Lubs and Ruddle (1970) from New ]-Iaven, USA, and Jacobs et al. (1974) from Edinburgh). In the other studies chromosome examination was only made of those children who had signs of chromosome abnormalities. Table 2. Seasonal variation in birth of patients with Edwards' syndrome Month of conception
Month of birth
Patients with Edwards' syndrome Canada England Denmark 1961--1965 1962--1967 1967--1973
10 11 12 i 2 3 4 5 6 7 8 9
1 2 3 4 5 6 7 8 9 10 11 12
3 1 4 2 3 2 ---1 ---
Total
16
-/
2 1
94%
1
22%
2
6%
5 4 2 4 3 3 27
1 3 2 [ 86°/o
-/I 78%
-- ~ 14% 1
/
7
Canada: Conen and Erkman (1966); England: Taylor (1968); Denmark: Present study.
Prevalence of Edwards' Syndrome
115
Table 3. Patients with karyotypes 47,XX¥, 47,XY¥, 47,XXX and 45,X. Distribution by month of birth and month of conception Month of birth Oct.
Total
Nov, Dee.
Jan.
Febr. March April May
June July
Aug. Sept.
Aug. Sept. Oct.
Nov. Dec.
Month of conception Jan. Observed Expected X2
Febr. YfarchApril May
June July
27 19 21 22 25 37 38 37 10 18 25 18 23.49 22.60 23.42 24.48 24.14 27.62 26.70 26.52 24.56 24.76 24.51 24.22
297 297.02
0.524 0.573 0.250 0.251 0.031 3.186 4.7~2 4.141 8.632 1.846 0.010 1.597
Z~, 11 df = 25.824
25.8.24
0.005 < P < 0.01
The expected rates are calculated on all live-born children in Denmark during the range of years of birth for the 297 patients with aneuploid sex chromosome abnormalities, i.e. 1896--1970. 47,XXY (n = 1 8 4 ) 47,XYY (n = 28) 47,XXX (n = 7) 45,X (n -~ 78)
45 40
"~°
Observed
{ n - 297)
35 "~
3o
®
25
m
t-]/\i
20 ¢.
¢
]5 Io
'I 1o
'2 11
13 12
4. . .5 . . 6 . 1 2 3
7 4
8 5
9 6
Io' 7
1'1 8
I '2 9
I~onth of conception Honth of birth
Fig. 1 Patients with karyotypes 47,XXY, 47,XYY, 47,XXX and 45,X. Distribution by month of birth and month of conception
as shown in t h e s t u d y b y Nielsen et al. (1973) a n d in Table 3. The t i m e of increase in conception of children w i t h E d w a r d s ' s y n d r o m e in our s t u d y , as well as in t h e s t u d y b y Cohen a n d E r k m a n from C a n a d a is M a y to J u l y a n d correlates with t h e finding of a significant seasonal v a r i a t i o n in conception of children with sex c h r o m o s o m e a b e r r a t i o n s registered in t h e Danish Cytogenetic Central l~egister as seen in Fig. 1 a n d T a b l e 3. T a b l e 2 shows t h e correlation b e t w e e n a s t u d y from C a n a d a a n d t h e p r e s e n t s t u d y of a significant increase in f r e q u e n c y of b i r t h of p a t i e n t s with E d w a r d s ' s y n d r o m e from J a n u a r y to June. The s t u d y b y T a y l o r from E n g l a n d of 27 cases with E d w a r d s ' s3mdrome shows quite t h e opposite with 78% of t h e p a t i e n t s
116
J. Nielsen et al.
with E d w a r d s ' s y n d r o m e born during t h e m o n t h s J u l y till D e c e m b e r as seen in Table 1. The v a r i a t i o n in f r e q u e n c y of t r i s o m y 18 in t h e studies from different p a r t s of t h e world, t h e seasonal v a r i a t i o n in b i r t h of children w i t h t r i s o m y 18, a n d clustering i n d i c a t e t h a t t h e r e are some e n v i r o n m e n t a l factors a m o n g t h e etiological factors of n o n d i s j u n c t i o n of chromosome 18 as p r e v i o u s l y f o u n d for nondisjunction of sex chromosomes. Comparison of clustering a n d seasonal v a r i a t i o n in b i r t h of children w i t h E d w a r d s ' s y n d r o m e in different p a r t s of t h e world should be m a d e in order to look for possible e n v i r o n m e n t a l etiological factors.
References Cohen, P. E., Erkman, B.: Frequency and occurrence of chromosomal syndromes II. Etrisomy. Amer. J. hum. Genet. 18, 387--398 (1966) Hecht, F., Motulsky, A. G., Gilbertt, E. R.: The no. 17--18 (E) trisomy syndrome. Studies on cytogenetics, dermatoglyphics, paternal age and linkage. J. Pediat. 63, 605 (1963) Heinrichs, E. H., Allen, S. W., Nelson, P. S. : Simultaneous 18-trisomy and 21-trisomy cluster. Lancet 1968 II, 468 Nielsen, J., Petersen, G. B., Therkelsen, A. J. : Seasonal variation in the birth of children with aneuploid chromosome abnormalities. Humangenetik 19, 67--74 (1973) Smith, D. W. : Autosomal abnormalities. Amer. J. Obstet. Gynec. 90, 1055 (1964) Taylor, A. I , Moores, E. C. : A sex chromatin survey of newborn children in two London hospitals. J. reed. Genet. 4, 258 (1967) Taylor, A. I. : Autosomal trisomy syndromes: A detailed study of 27 cases of Edwards' syndrome and 27 cases of Patau's syndrome. J. med. Genet. 5, 227--252 (1968) Taylor, A. I., t~oberts, J. F. (quoted as unpublished by Taylor, A. I.) in J. reed. Genet. 5, 227--252 (1968) Dr. J. Nielsen The Cytogenetic Laboratory Arhus State Hospital l~isskov, Denmark
