Sirenomelia By Maria
in an Identical Di Lorenzo,
Mary
Twin: A Case Report
L. Brandt,
Montreal,
and Annie
Veilleux
Quebec
l Sirenomelia, or the mermaid syndrome, is the most extreme example of the caudal regression syndrome. It invariably presents with lower limb fusion, sacral and pelvic bony anomalies, absent external genitalia, anal imperforation, and renal agenesis or dysgenesis. Because of the resultant oligohydramnios, these infants most often have Potter’s facies and pulmonary hypoplasia. There are approximately 300 cases reported in the literature, 15% of which are associated with twinning, most often monozygotic. The syndrome of caudal regression is thought to be the result of injury to the caudal mesoderm early in gestation. It has been suggested that the association of the most extreme form of caudal regression, sirenomelia, with monozygotic twinning may represent developmental arrest of the primitive streak, with creation of a second primitive streak that gives rise to the usually normal twin. The embryology of the various presentations of the caudal regression syndrome may be further delineated by studying infants with this dramatic and fatal syndrome. Copyright o 7997 by W.B. Saunders Company INDEX WORDS:
Sirenomelia;
mermaid baby.
S
IRENOMELIA is the term used to describe fusion of the lower extremities. It is associated with malformations of the vertebrae and the genitourinary system and with anal imperforation. Also known as the mermaid syndrome, this term is derived from the mythological creatures described by the ancient Greeks and Romans. It was not until 1898 that Ballantyne reported more objective evidence of the existence of such a malformation.’ Sirenomelia is extremely rare, with an incidence of 1 in 60,000 births.’ Contrary to popular belief, there is a male predominance with a 2.7:1 male to female ratio.3 There is also an apparent lOO-fold increase in the incidence of mermaid syndrome in monozygotic twin births.4 The severity of the associated malformations are not compatible with life. There are approximately 300 cases of mermaid syndrome reported in the literature.’ We wish to report an additional case of sirenomelia in a live birth involving a monozygotic twin. From the Departments of Sueety and Neonatology, Sainte-Justine Hospital, University of Montreal, Montreal, Quebec. Presented at the 22nd Annual Meeting of the Canadian Association of Paediatric Surgeons, St John’s, Newfoundland, August 22-25,199O. Address reprint requests to Maria Di Lorenzo, MD, Ste-Justine Hospital, 3175 Ste-Catherine Rd, Montreal, Quebec H3T IC5, Canada. Copyright o 1991 by kK!B. Saunders Company 0022-3468/9112611-002I$O3.00/0
1334
Fig 1.
Sirenomelic twin. (A) Frontal view; (8) donal view.
CASE
REPORT
This infant boy was the 2,725-g, 3%week product of an uneventful pregnancy in a normal healthy woman. His monozygotic male twin was born without anomaly. A prenatal ultrasound at 18 weeks’ gestation was suggestive of caudal regression in one twin but normal at 19 weeks. Physical examination at birth showed the infant to be eupneic with a normal facies. There was fusion of the lower limbs with bilateral presence of hip, knee, and ankle joints, a hypogastric hernia, and absent external genitalia and anus (Fig 1). Radiographs showed normal femurs, tibias, and fibulas, with soft tissue fusion between the lower limbs (Fig 2), nonfusion of the bodies of the lower lumbar vertebrae, sacral agenesis, and malformation of the pelvis (Fig 3). Ultrasound and computed tomography demonstrated the absence of both kidneys and bladder. The infant was sedated and allowed to die.
~OurnatofPediafricSurgery,
Vol26,
No 11 (November), 1991: pp 1334-1336
1335
SIRENOMELIA IN AN IDENTICAL TWIN
In 1970, Davies et al determined that sirenomelia results from injury to the caudal mesoderm between 28 and 32 days of fetal development.4 A wedge-like defect occurs in the primitive streak at the lumbar and sacral areas. Midline structures including cloaca1 and urogenital derivatives are destroyed, allowing the halves of the hind limb buds to move medially and dorsally fusing along their postaxial surfaces. They also suggested that developmental arrest of the primitive streak initiates formation of a second primitive streak, giving rise to a second normal embryo. This may account for the high incidence of sirenomelia in twins.4 Smith et al also have suggested that the VATER association, monozygotic twins, and sirenomelia may represent varying degrees of the same defect.6 In 1980, Gardner and Breuer’ proposed that neural _
cutaneous polypoid midline structure. The infant also had a high
DISCUSSION
In 1961, Duhamel’ proposed that a defect in the formation of the caudal region was at the origin of a spectrum of malformations including anal imperforation and the mermaid syndrome. Small lesions would cause imperforate anus and mild vertebral anomalies, whereas larger lesions would cause urinary or genital anomalies. Extreme lesions would lead to lower limb fusion and sirenomelia. He coined the term “syndrome of caudal regression.”
Fig 3. Lumbar vertebral nonfusion, sacral agenesis, and malformation of pelvis.
1336
DI LORENZO, BRANDT. AND VEILLEUX
rotation of the mesoderm by 180”. This rotation would cause fusion of the lower limb buds, closing off the midline primitive gut and urethra. Potter described a sequence of anomalies resulting from renal agenesis and oligohydramnios that lead to facial deformities and pulmonary hypoplasia.* The present patient presented with normal facies and lungs because his monozygotic twin had normal renal function and both twins were contained in one amnionic sac. A genetic mechanism leading to sirenomelia seems unlikely, due to the absence of familial cases in the reported literature. Vascular disruption or hypoperfusion is a well-known factor in the pathogenesis of many structural defects in the fetus.’ Disruption or
malformation of the primitive streak’s caudal vasculature could lead to malformation of structures derived from its mesoderm.’ Retinoic acid” and cyclophosphamide” administered to pregnant mice and hamsters produce limb malformations including sirenomelia, but no such exposure has been recorded in mothers of mermaid babies. Maternal diabetes and caudal regression syndrome are well-known associations.12 Only 2 of 80 cases reported by Stocker and Heifetz’ involved diabetic mothers. To date, no single teratologic agent can be incriminated in the etiology of sirenomelia. We must deduce this rare and dramatic malformation to be a random occurrence.
REFERENCES 1. Stocker JT, Heifetz SA: Sirenomelia: A morphological study of 33 cases and review of the literature. Perspect Pediatr Pathol 10:7-50, 1987 2. Crawford A, Imail SR, Wiggleseworth JS: A monopodial sireniform monster with dermatoglyphic and cytogenetic studies. J Med Genet 3:212-216,1966 3. Smith DW: Recognizable patterns of human malformations, in Genetic, Embryologic and Clinical Aspects (ed 3). Philadelphia, PA, Saunders, 1970, pp 481-486 4. Davies J, ChagetYE, Nance WE: Symmelia in one of monozygotic twins. Teratology 4:367-378,197O 5. Duhamel B: From the mermaid to anal imperforation. The syndrome of caudal regression. Arch Dis Child 36:152-155,196l 6. Smith DW, Bartlett C, Harrol LM: Monozygotic twinning and the Duhamel anomalad (imperforate anus to sirenomelia). Birth Defects 12:53-63, 1976 7. Gardner NJ, Breuer AC: Anomalies of heart, spleen, kidneys,
gut and limbs may result from an overdistended hypothesis. Pediatrics 65:508-514,198O
neural tube. A
8. Cohen MM Jr: Dysmorphology, syndromology and genetics, in McCarthy JG (ed): Plastic Surgery, vol 1. Philadelphia, PA, 1990, pp 69-112 9. Hoyme HE: The pathogenesis of sirenomelia. An editorial comment. Teratology 38:485-486,1988 10. Shenefelt RE: Morphogenesis of malformation in hamsters caused by retinoic acid. Relation to dose and stage at treatment. Teratology5:103-118,1972 11. Manson JM, Smith CC: Influence of cyclophosphamide and 4-ketocyclophos-phamide on mouse limb development. Teratology 15:291-299,1977 12. Passarge E, Leng W: Syndrome of caudal regression in infants of diabetic mothers: Observation of further cases. Pediatrics 37:672-675,1966
in an Identical Di Lorenzo,
Mary
Twin: A Case Report
L. Brandt,
Montreal,
and Annie
Veilleux
Quebec
l Sirenomelia, or the mermaid syndrome, is the most extreme example of the caudal regression syndrome. It invariably presents with lower limb fusion, sacral and pelvic bony anomalies, absent external genitalia, anal imperforation, and renal agenesis or dysgenesis. Because of the resultant oligohydramnios, these infants most often have Potter’s facies and pulmonary hypoplasia. There are approximately 300 cases reported in the literature, 15% of which are associated with twinning, most often monozygotic. The syndrome of caudal regression is thought to be the result of injury to the caudal mesoderm early in gestation. It has been suggested that the association of the most extreme form of caudal regression, sirenomelia, with monozygotic twinning may represent developmental arrest of the primitive streak, with creation of a second primitive streak that gives rise to the usually normal twin. The embryology of the various presentations of the caudal regression syndrome may be further delineated by studying infants with this dramatic and fatal syndrome. Copyright o 7997 by W.B. Saunders Company INDEX WORDS:
Sirenomelia;
mermaid baby.
S
IRENOMELIA is the term used to describe fusion of the lower extremities. It is associated with malformations of the vertebrae and the genitourinary system and with anal imperforation. Also known as the mermaid syndrome, this term is derived from the mythological creatures described by the ancient Greeks and Romans. It was not until 1898 that Ballantyne reported more objective evidence of the existence of such a malformation.’ Sirenomelia is extremely rare, with an incidence of 1 in 60,000 births.’ Contrary to popular belief, there is a male predominance with a 2.7:1 male to female ratio.3 There is also an apparent lOO-fold increase in the incidence of mermaid syndrome in monozygotic twin births.4 The severity of the associated malformations are not compatible with life. There are approximately 300 cases of mermaid syndrome reported in the literature.’ We wish to report an additional case of sirenomelia in a live birth involving a monozygotic twin. From the Departments of Sueety and Neonatology, Sainte-Justine Hospital, University of Montreal, Montreal, Quebec. Presented at the 22nd Annual Meeting of the Canadian Association of Paediatric Surgeons, St John’s, Newfoundland, August 22-25,199O. Address reprint requests to Maria Di Lorenzo, MD, Ste-Justine Hospital, 3175 Ste-Catherine Rd, Montreal, Quebec H3T IC5, Canada. Copyright o 1991 by kK!B. Saunders Company 0022-3468/9112611-002I$O3.00/0
1334
Fig 1.
Sirenomelic twin. (A) Frontal view; (8) donal view.
CASE
REPORT
This infant boy was the 2,725-g, 3%week product of an uneventful pregnancy in a normal healthy woman. His monozygotic male twin was born without anomaly. A prenatal ultrasound at 18 weeks’ gestation was suggestive of caudal regression in one twin but normal at 19 weeks. Physical examination at birth showed the infant to be eupneic with a normal facies. There was fusion of the lower limbs with bilateral presence of hip, knee, and ankle joints, a hypogastric hernia, and absent external genitalia and anus (Fig 1). Radiographs showed normal femurs, tibias, and fibulas, with soft tissue fusion between the lower limbs (Fig 2), nonfusion of the bodies of the lower lumbar vertebrae, sacral agenesis, and malformation of the pelvis (Fig 3). Ultrasound and computed tomography demonstrated the absence of both kidneys and bladder. The infant was sedated and allowed to die.
~OurnatofPediafricSurgery,
Vol26,
No 11 (November), 1991: pp 1334-1336
1335
SIRENOMELIA IN AN IDENTICAL TWIN
In 1970, Davies et al determined that sirenomelia results from injury to the caudal mesoderm between 28 and 32 days of fetal development.4 A wedge-like defect occurs in the primitive streak at the lumbar and sacral areas. Midline structures including cloaca1 and urogenital derivatives are destroyed, allowing the halves of the hind limb buds to move medially and dorsally fusing along their postaxial surfaces. They also suggested that developmental arrest of the primitive streak initiates formation of a second primitive streak, giving rise to a second normal embryo. This may account for the high incidence of sirenomelia in twins.4 Smith et al also have suggested that the VATER association, monozygotic twins, and sirenomelia may represent varying degrees of the same defect.6 In 1980, Gardner and Breuer’ proposed that neural _
cutaneous polypoid midline structure. The infant also had a high
DISCUSSION
In 1961, Duhamel’ proposed that a defect in the formation of the caudal region was at the origin of a spectrum of malformations including anal imperforation and the mermaid syndrome. Small lesions would cause imperforate anus and mild vertebral anomalies, whereas larger lesions would cause urinary or genital anomalies. Extreme lesions would lead to lower limb fusion and sirenomelia. He coined the term “syndrome of caudal regression.”
Fig 3. Lumbar vertebral nonfusion, sacral agenesis, and malformation of pelvis.
1336
DI LORENZO, BRANDT. AND VEILLEUX
rotation of the mesoderm by 180”. This rotation would cause fusion of the lower limb buds, closing off the midline primitive gut and urethra. Potter described a sequence of anomalies resulting from renal agenesis and oligohydramnios that lead to facial deformities and pulmonary hypoplasia.* The present patient presented with normal facies and lungs because his monozygotic twin had normal renal function and both twins were contained in one amnionic sac. A genetic mechanism leading to sirenomelia seems unlikely, due to the absence of familial cases in the reported literature. Vascular disruption or hypoperfusion is a well-known factor in the pathogenesis of many structural defects in the fetus.’ Disruption or
malformation of the primitive streak’s caudal vasculature could lead to malformation of structures derived from its mesoderm.’ Retinoic acid” and cyclophosphamide” administered to pregnant mice and hamsters produce limb malformations including sirenomelia, but no such exposure has been recorded in mothers of mermaid babies. Maternal diabetes and caudal regression syndrome are well-known associations.12 Only 2 of 80 cases reported by Stocker and Heifetz’ involved diabetic mothers. To date, no single teratologic agent can be incriminated in the etiology of sirenomelia. We must deduce this rare and dramatic malformation to be a random occurrence.
REFERENCES 1. Stocker JT, Heifetz SA: Sirenomelia: A morphological study of 33 cases and review of the literature. Perspect Pediatr Pathol 10:7-50, 1987 2. Crawford A, Imail SR, Wiggleseworth JS: A monopodial sireniform monster with dermatoglyphic and cytogenetic studies. J Med Genet 3:212-216,1966 3. Smith DW: Recognizable patterns of human malformations, in Genetic, Embryologic and Clinical Aspects (ed 3). Philadelphia, PA, Saunders, 1970, pp 481-486 4. Davies J, ChagetYE, Nance WE: Symmelia in one of monozygotic twins. Teratology 4:367-378,197O 5. Duhamel B: From the mermaid to anal imperforation. The syndrome of caudal regression. Arch Dis Child 36:152-155,196l 6. Smith DW, Bartlett C, Harrol LM: Monozygotic twinning and the Duhamel anomalad (imperforate anus to sirenomelia). Birth Defects 12:53-63, 1976 7. Gardner NJ, Breuer AC: Anomalies of heart, spleen, kidneys,
gut and limbs may result from an overdistended hypothesis. Pediatrics 65:508-514,198O
neural tube. A
8. Cohen MM Jr: Dysmorphology, syndromology and genetics, in McCarthy JG (ed): Plastic Surgery, vol 1. Philadelphia, PA, 1990, pp 69-112 9. Hoyme HE: The pathogenesis of sirenomelia. An editorial comment. Teratology 38:485-486,1988 10. Shenefelt RE: Morphogenesis of malformation in hamsters caused by retinoic acid. Relation to dose and stage at treatment. Teratology5:103-118,1972 11. Manson JM, Smith CC: Influence of cyclophosphamide and 4-ketocyclophos-phamide on mouse limb development. Teratology 15:291-299,1977 12. Passarge E, Leng W: Syndrome of caudal regression in infants of diabetic mothers: Observation of further cases. Pediatrics 37:672-675,1966
