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Familial bicornuate and double uterus
Familial bicornuate and double uterus WOLFE
Z.
POLISHUK,
MOSHE
A.
RON,
Jerusalem,
M.D. M.D.
Israel
This is a report of three families in whom two or more sisters had an identical Miillerian duct fusion defect. In one of the families two sisters had a double uterus. In the other two families, four and two sisters had a bicornuate uterus. The evidence for a familial and genetic etiology of uterine fusion defects reviewed. The prior knowledge of the existence of a uterine anomaly may have important implications in the antenatal care and management. This knowledge may also be of benefit to the patients’ siblings, who should be investigated for a possible uterine fusion defect.
THE MOST significant events in the embryologic formation of the reproductive tract commence around the fifth or sixth week of fetal life. It is therefore assumed that the basic cause for a partial or complete failure of Miillerian duct fusion occurs at this time.l Of the possible causes, fetal environmental factors of maternal or placental origin have been implicated. These include poor nutrition, metabolic disorders, viral diseases, placental abnormalities, and exposure to toxic drugs.’ Most women with Miillerian duct fusion defects are otherwise normal, except for some associated urinary tract anomalies, such as renal agenesis, horse-shoe kidney, ectopic kidney, and others.” For these reasons, the possibility of hereditary factors or germ plasm defects hive been given little consideration in the etiology of this relatively common anomaly of defective fusion of the Miillerian duct. Nikiforuk was the first to describe in 1938 two sisters, one with uterus didelphys and
the other with a double vagina. Ways reported a mother with bicornuate uterus who gave birth to a dead fetus with the same malformation. He later described a case of mother and child and two sisters with the same genital malformation.” Until 1961, only nine families had been described with at least two of its members having a genital tract malformation.7-‘” HayI in 1961 published a report of 25 families involving 59 women, of whom 56 had some form of uterine anomaly. In two of these families, the uterine anomaly consisted of bicornuate and arcuate uteri; in the other 23 families, the anomalies were of minor degrees. The following is a report of three families in whom at least two members had a marked uterine anomaly with a correspondingly poor obstetric history. One of these families is the first reported with familial double uterus. Case
reports
Family I. From the Department Gynecology, Hadassah Hospital. Received 1973. Revised Accepted Reprint E;fyh
for publication December December
of Obstetrics University
and
September
5,
is
This
family
is of Algerian
origin
and
the parents arc not related. There are three brothers and five sisters in this family. Two of the sisters are described in cases 1 and 2. The mother of this family has had 14 pregnancies, of which five terminated in early and late abortions and one was a stillbirth. Case I. S. N., 19 years of age, is a healthy woman with well-developed secondary sex char-
18, 1973. 20, 1973.
requests: Dr. W. Z. Polishuk, University Hospital, Jerusalem,
acteristics
982
and normal
menses. Both
her preg-
Fig. 1. Family didelphys.
Fig. 2. Family didelphys. nanc the rxan turn open norn
I,
I,
case
case
1, S. N.
2, D.
Habitual
A.
Sister
premature
of S. N.
ies terminated in spontaneous abortions in Isixth and second months of gestation. Pelvic lination revealed a longitudinal vaginal sepin the middle third. There were two cervical ings and the uterus was felt as a single, lal-sized, retroverted body.
Familial
bicornuate
delivery.
Hysterography
showing
uterus
Hysterography
showing
uterus
(case
After showed had three nated in Case sterility
I).
and
double
uterus
983
excision of the septum, a hysterography a double uterus (Fig. 1). The patient more pregnancies, all of which termipremature deliveries. 2. D. A., 24 years of age, had primary of six years’ duration. She was well
984
Polishuk
and
Fig. 3. Family left horn.
August 1, 1974 Am. J. Obstet. Gynecol.
Ron
II,
Fig. 4. Family II, showing a bicornuate
case
3, S. H.
Hysterography
case 4, S. G. Sister uterus.
of S. H.
and healthy, with normal menstrual devl eloped cycl es. Three years earlier she had had an excision of a vaginal septum. On pelvic examination a dl ouble cervix was found, with the uterus as a nor1 nal-sized single mass. On hysterography (Fig. uterus was found. The patient’s 2) a double steri lity was found to be due to a severe oligl aspermia.
showing
(case
3)
bicornuate
and
A. A.
uterus.
(case
5).
Air
bubbles
in
Hysterography
Family II. This family is of Russian o rigin and the parents are not related. There are four sisters and one brother. The mother has hat d no abortions or other obstetric pathology. All si stem were essentially healthy and well developed and had normal menstrual cycles. A short obst etric history of these sisters is given in cases 3 to 6. Case 3. S. H., 25 years of age, lost her first
Volume Number
119 7
Familial
bicornuate
and
double
uterus
985
Fig. 5. Family II, case 5, A. A. Sister of S. H. (case 3) and S. G. (case 4). Hysterography showing a retroflexed bicornuate uterus. three fetuses in early spontaneous abortions. Hysterography revealed a bicornuate uterus (Fig. 3). The fourth and fifth pregnancies terminated in the term delivery of a 3,600 gram normal male child and a 2,800 gram normal female child. Case 4. S. G., 30 years of age, has had three consecutive early abortions. Pelvic examination was essentially normal, except for a short and wide cervical canal. Hysterography (Fig. 4) showed a bicornuate uterus. Her fourth pregnancy terminated in the delivery of a normal term male child. In her fifth pregnancy the patient aborted following premature rupture of membranes in the sixth month. CaJe 5. A. A., a 38-year-old woman, had 10 pregnancies. The first three terminated in spontaneous abortions in the second and third months. Her subsequent seven pregnancies terminated in normal term deliveries. Of these children the two living females were presumably normal. A hysterography performed after her last abortion showed a bicornuate uterus (Fig. 5). Case 6. R. A., 44 years of age, had seven pregnancies. The first ended in a missed abortion in the third month and the second terminated in a premature breech delivery. The placenta had to be manually removed, at which time she was found to have a bicornuate uterus. No hysterography was performed. The third preg-
nancy was an early second-month abortion. Her fourth and fifth pregnancies terminated in breech deliveries and the placentas had to be manually removed. Her sixth pregnancy was a term vertex delivery of an apparently normal 4,500 gram female child with a spontaneous placental delivery. Her seventh and last pregnancy terminated in a term breech delivery and spontaneous separation of the placenta. Family III. This is an Iraqi family of seven sisters and two brothers of whom two brothers and two sisters have migrated to this country. The mother has had a total of 11 pregnancies, of which two were miscarriages. The obstetric history and hysterography of only two sisters is available. Case 7. S. S., 27 years of age, had two early abortions. A hysterography was performed because of a suspected submucous fibroid. This revealed a bicornuate uterus (Fig. 6). In her third pregnancy she developed pre-eclamptic toxemia and the pregnancy was terminated by a cesarean section in the thirty-fifth week. A premature male child weighing 2,100 grams was born. Case 8. D. S., 35 years of age, sister of S. S. (case 7)) had seven pregnancies. The first five pregnancies terminated in early and missed abortions. Hysterography revealed a bicornuate uterus (Fig. 7). Following a Strassman operation she had two more pregnancies which terminated in
986
Polishuk
and
August 1, 1974 4m. J. Obstet. Gynecol.
Ron
Fig. 6. Family III, case 7, S. S. Recurrent uterus.
early abortion.
Hysterography
Fig. 7. Family III, case 8, D. S. Sister of S. S. (case 6). Habitual showing a bicornuate uterus. the and
delivery by cesarean section of two viable normal male children. C omment
T- ‘he
familial and genetic nature on defects has been the subject fusic :rimental and clinical studies. expc
of uterine of various Hain and
showing bicornuate
aborter. Hysterography
in Robertson’” succeeded experimentally his rearing rats with urogenital anomalies. T pointed to a possible recessive trait as ithe underlying mechanism involved in agent :sis of the kidney and may similarly apply to uterine fusion defects. Halbert and Chr -istakosl’; in 1970 described a pair of mono. zy-
Volume Number
119 7
gotic twins, one with uterus didelphys and the other with no malformations. This suggests that the defect may have occurred at or after such time as the events responsible for twinning. Caprano and CohenI” have performed cytogenetic studies on 11 femaIes with various Miillerian duct duplication anomalies and found all of them to have a normal karyotype. The cases reported by us in this paper add further clinical evidence to a possible genetic factor in the etiology of uterine anomalies. It would appear that we are dealing with a dominant autosomal gene. The familial nature of the uterine anomaly in the three families described resulted from the fact that the patients consulted the same
Familial
bicornuate
and double
uterus
987
gynecologist for their poor obstetric course. This brings up the possibility that the familial nature of the uterine anomalies may be more frequent than we think. The clinical importance of the various forms of faulty fusion of the Miillerian duct lies in the effect these may have upon the course of pregnancy and delivery. The obstetric complications in the eight cases reported above included recurrent and habitual abortion, late abortion and premature delivery, malpresentation, premature rupture of membranes, retained placenta, and an over-all high fetal loss. The prior knowledge of the existence of a uterine anomaly may have important implications in the antenatal care and management of the patient concerned.
REFERENCES
1. Green, T. H.: Gynecology, Boston, 1965, Little, Brown & Company, p. 52. 2. Jarcho, J.: Am. J. Surg. 71: 106, 1946. 3. 4. 5. 6. 7. 8.
Wharton, L. R.: AM. J. OBSTET. GYNECOL. 53: 37, 1947. Nikiforuk, N. C.: Can. Med. Assoc. J. 38: 175, 1938. Way, S.: J. Obstet. Gynecol. Brit. Emp. 52: 325, 1945. Way, S.: J. Obstet. Gynecol. Brit. Emp. 52: 469, 1947. Holmes, J. A.: Br. Med. J. 1: 1144, 1956. Jones, H. W., Delfes, E., Jones, S. G.: AM. J. OBSTET. GYNECOL. 72: 865, 1956.
9. Stevenson, 10. 11. 12. 13. 14.
A. C., Dudgeon, M. Y., and McClure, H. I.: Ann. Hum. Genet. 23: 395, 1959. Woolf, R. B., and Allen, W. M.: Obstet. Gynecol. 2: 236, 1953. Hay, D.: J. Obstet. Gynecol. Br. Commonw. 68: 361, 1961. Hain, A. N., and Robertson, E. M.: J. Anat. (Lond.) 70: 566, 1936. Halbert. D. R.. and Christakos. A. C.: Obstet. Gynecoi. 36: 388, 1970. ’ Caprano, V. J., and Cohen, M. M.: Obstet. Gynecol. 33: 647, 1969.
Z.
POLISHUK,
MOSHE
A.
RON,
Jerusalem,
M.D. M.D.
Israel
This is a report of three families in whom two or more sisters had an identical Miillerian duct fusion defect. In one of the families two sisters had a double uterus. In the other two families, four and two sisters had a bicornuate uterus. The evidence for a familial and genetic etiology of uterine fusion defects reviewed. The prior knowledge of the existence of a uterine anomaly may have important implications in the antenatal care and management. This knowledge may also be of benefit to the patients’ siblings, who should be investigated for a possible uterine fusion defect.
THE MOST significant events in the embryologic formation of the reproductive tract commence around the fifth or sixth week of fetal life. It is therefore assumed that the basic cause for a partial or complete failure of Miillerian duct fusion occurs at this time.l Of the possible causes, fetal environmental factors of maternal or placental origin have been implicated. These include poor nutrition, metabolic disorders, viral diseases, placental abnormalities, and exposure to toxic drugs.’ Most women with Miillerian duct fusion defects are otherwise normal, except for some associated urinary tract anomalies, such as renal agenesis, horse-shoe kidney, ectopic kidney, and others.” For these reasons, the possibility of hereditary factors or germ plasm defects hive been given little consideration in the etiology of this relatively common anomaly of defective fusion of the Miillerian duct. Nikiforuk was the first to describe in 1938 two sisters, one with uterus didelphys and
the other with a double vagina. Ways reported a mother with bicornuate uterus who gave birth to a dead fetus with the same malformation. He later described a case of mother and child and two sisters with the same genital malformation.” Until 1961, only nine families had been described with at least two of its members having a genital tract malformation.7-‘” HayI in 1961 published a report of 25 families involving 59 women, of whom 56 had some form of uterine anomaly. In two of these families, the uterine anomaly consisted of bicornuate and arcuate uteri; in the other 23 families, the anomalies were of minor degrees. The following is a report of three families in whom at least two members had a marked uterine anomaly with a correspondingly poor obstetric history. One of these families is the first reported with familial double uterus. Case
reports
Family I. From the Department Gynecology, Hadassah Hospital. Received 1973. Revised Accepted Reprint E;fyh
for publication December December
of Obstetrics University
and
September
5,
is
This
family
is of Algerian
origin
and
the parents arc not related. There are three brothers and five sisters in this family. Two of the sisters are described in cases 1 and 2. The mother of this family has had 14 pregnancies, of which five terminated in early and late abortions and one was a stillbirth. Case I. S. N., 19 years of age, is a healthy woman with well-developed secondary sex char-
18, 1973. 20, 1973.
requests: Dr. W. Z. Polishuk, University Hospital, Jerusalem,
acteristics
982
and normal
menses. Both
her preg-
Fig. 1. Family didelphys.
Fig. 2. Family didelphys. nanc the rxan turn open norn
I,
I,
case
case
1, S. N.
2, D.
Habitual
A.
Sister
premature
of S. N.
ies terminated in spontaneous abortions in Isixth and second months of gestation. Pelvic lination revealed a longitudinal vaginal sepin the middle third. There were two cervical ings and the uterus was felt as a single, lal-sized, retroverted body.
Familial
bicornuate
delivery.
Hysterography
showing
uterus
Hysterography
showing
uterus
(case
After showed had three nated in Case sterility
I).
and
double
uterus
983
excision of the septum, a hysterography a double uterus (Fig. 1). The patient more pregnancies, all of which termipremature deliveries. 2. D. A., 24 years of age, had primary of six years’ duration. She was well
984
Polishuk
and
Fig. 3. Family left horn.
August 1, 1974 Am. J. Obstet. Gynecol.
Ron
II,
Fig. 4. Family II, showing a bicornuate
case
3, S. H.
Hysterography
case 4, S. G. Sister uterus.
of S. H.
and healthy, with normal menstrual devl eloped cycl es. Three years earlier she had had an excision of a vaginal septum. On pelvic examination a dl ouble cervix was found, with the uterus as a nor1 nal-sized single mass. On hysterography (Fig. uterus was found. The patient’s 2) a double steri lity was found to be due to a severe oligl aspermia.
showing
(case
3)
bicornuate
and
A. A.
uterus.
(case
5).
Air
bubbles
in
Hysterography
Family II. This family is of Russian o rigin and the parents are not related. There are four sisters and one brother. The mother has hat d no abortions or other obstetric pathology. All si stem were essentially healthy and well developed and had normal menstrual cycles. A short obst etric history of these sisters is given in cases 3 to 6. Case 3. S. H., 25 years of age, lost her first
Volume Number
119 7
Familial
bicornuate
and
double
uterus
985
Fig. 5. Family II, case 5, A. A. Sister of S. H. (case 3) and S. G. (case 4). Hysterography showing a retroflexed bicornuate uterus. three fetuses in early spontaneous abortions. Hysterography revealed a bicornuate uterus (Fig. 3). The fourth and fifth pregnancies terminated in the term delivery of a 3,600 gram normal male child and a 2,800 gram normal female child. Case 4. S. G., 30 years of age, has had three consecutive early abortions. Pelvic examination was essentially normal, except for a short and wide cervical canal. Hysterography (Fig. 4) showed a bicornuate uterus. Her fourth pregnancy terminated in the delivery of a normal term male child. In her fifth pregnancy the patient aborted following premature rupture of membranes in the sixth month. CaJe 5. A. A., a 38-year-old woman, had 10 pregnancies. The first three terminated in spontaneous abortions in the second and third months. Her subsequent seven pregnancies terminated in normal term deliveries. Of these children the two living females were presumably normal. A hysterography performed after her last abortion showed a bicornuate uterus (Fig. 5). Case 6. R. A., 44 years of age, had seven pregnancies. The first ended in a missed abortion in the third month and the second terminated in a premature breech delivery. The placenta had to be manually removed, at which time she was found to have a bicornuate uterus. No hysterography was performed. The third preg-
nancy was an early second-month abortion. Her fourth and fifth pregnancies terminated in breech deliveries and the placentas had to be manually removed. Her sixth pregnancy was a term vertex delivery of an apparently normal 4,500 gram female child with a spontaneous placental delivery. Her seventh and last pregnancy terminated in a term breech delivery and spontaneous separation of the placenta. Family III. This is an Iraqi family of seven sisters and two brothers of whom two brothers and two sisters have migrated to this country. The mother has had a total of 11 pregnancies, of which two were miscarriages. The obstetric history and hysterography of only two sisters is available. Case 7. S. S., 27 years of age, had two early abortions. A hysterography was performed because of a suspected submucous fibroid. This revealed a bicornuate uterus (Fig. 6). In her third pregnancy she developed pre-eclamptic toxemia and the pregnancy was terminated by a cesarean section in the thirty-fifth week. A premature male child weighing 2,100 grams was born. Case 8. D. S., 35 years of age, sister of S. S. (case 7)) had seven pregnancies. The first five pregnancies terminated in early and missed abortions. Hysterography revealed a bicornuate uterus (Fig. 7). Following a Strassman operation she had two more pregnancies which terminated in
986
Polishuk
and
August 1, 1974 4m. J. Obstet. Gynecol.
Ron
Fig. 6. Family III, case 7, S. S. Recurrent uterus.
early abortion.
Hysterography
Fig. 7. Family III, case 8, D. S. Sister of S. S. (case 6). Habitual showing a bicornuate uterus. the and
delivery by cesarean section of two viable normal male children. C omment
T- ‘he
familial and genetic nature on defects has been the subject fusic :rimental and clinical studies. expc
of uterine of various Hain and
showing bicornuate
aborter. Hysterography
in Robertson’” succeeded experimentally his rearing rats with urogenital anomalies. T pointed to a possible recessive trait as ithe underlying mechanism involved in agent :sis of the kidney and may similarly apply to uterine fusion defects. Halbert and Chr -istakosl’; in 1970 described a pair of mono. zy-
Volume Number
119 7
gotic twins, one with uterus didelphys and the other with no malformations. This suggests that the defect may have occurred at or after such time as the events responsible for twinning. Caprano and CohenI” have performed cytogenetic studies on 11 femaIes with various Miillerian duct duplication anomalies and found all of them to have a normal karyotype. The cases reported by us in this paper add further clinical evidence to a possible genetic factor in the etiology of uterine anomalies. It would appear that we are dealing with a dominant autosomal gene. The familial nature of the uterine anomaly in the three families described resulted from the fact that the patients consulted the same
Familial
bicornuate
and double
uterus
987
gynecologist for their poor obstetric course. This brings up the possibility that the familial nature of the uterine anomalies may be more frequent than we think. The clinical importance of the various forms of faulty fusion of the Miillerian duct lies in the effect these may have upon the course of pregnancy and delivery. The obstetric complications in the eight cases reported above included recurrent and habitual abortion, late abortion and premature delivery, malpresentation, premature rupture of membranes, retained placenta, and an over-all high fetal loss. The prior knowledge of the existence of a uterine anomaly may have important implications in the antenatal care and management of the patient concerned.
REFERENCES
1. Green, T. H.: Gynecology, Boston, 1965, Little, Brown & Company, p. 52. 2. Jarcho, J.: Am. J. Surg. 71: 106, 1946. 3. 4. 5. 6. 7. 8.
Wharton, L. R.: AM. J. OBSTET. GYNECOL. 53: 37, 1947. Nikiforuk, N. C.: Can. Med. Assoc. J. 38: 175, 1938. Way, S.: J. Obstet. Gynecol. Brit. Emp. 52: 325, 1945. Way, S.: J. Obstet. Gynecol. Brit. Emp. 52: 469, 1947. Holmes, J. A.: Br. Med. J. 1: 1144, 1956. Jones, H. W., Delfes, E., Jones, S. G.: AM. J. OBSTET. GYNECOL. 72: 865, 1956.
9. Stevenson, 10. 11. 12. 13. 14.
A. C., Dudgeon, M. Y., and McClure, H. I.: Ann. Hum. Genet. 23: 395, 1959. Woolf, R. B., and Allen, W. M.: Obstet. Gynecol. 2: 236, 1953. Hay, D.: J. Obstet. Gynecol. Br. Commonw. 68: 361, 1961. Hain, A. N., and Robertson, E. M.: J. Anat. (Lond.) 70: 566, 1936. Halbert. D. R.. and Christakos. A. C.: Obstet. Gynecoi. 36: 388, 1970. ’ Caprano, V. J., and Cohen, M. M.: Obstet. Gynecol. 33: 647, 1969.