Sirenomelia: An epidemiologic study in a large dataset from the International Clearinghouse of Birth Defects Surveillance and Research, and literature review

Abstract

Sirenomelia is a very rare limb anomaly in which the normally paired lower limbs are replaced by a single midline limb. This study describes the prevalence, associated malformations, and maternal characteristics among cases with sirenomelia. Data originated from 19 birth defect surveillance system members of the International Clearinghouse for Birth Defects Surveillance and Research, and were reported according to a single pre-established protocol. Cases were clinically evaluated locally and reviewed centrally. A total of 249 cases with sirenomelia were identified among 25,290,172 births, for a prevalence of 0.98 per 100,000, with higher prevalence in the Mexican registry. An increase of sirenomelia prevalence with maternal age less than 20 years was statistically significant. The proportion of twinning was 9%, higher than the 1% expected. Sex was ambiguous in 47% of cases, and no different from expectation in the rest. The proportion of cases born alive, premature, and weighting less than 2,500 g were 47%, 71.2%, and 88.2%, respectively. Half of the cases with sirenomelia also presented with genital, large bowel, and urinary defects. About 10-15% of the cases had lower spinal column defects, single or anomalous umbilical artery, upper limb, cardiac, and central nervous system defects. There was a greater than expected association of sirenomelia with other very rare defects such as bladder exstrophy, cyclopia/holoprosencephaly, and acardia-acephalus. The application of the new biological network analysis approach, including molecular results, to these associated very rare diseases is suggested for future studies.

Sirenomelia: two cases in Cali, Colombia

“…In the cases being reported, the mothers did not present any alterations in the glycaemic tests performed during the antenatal control, eliminating diabetes as the aetiologic agent. Furthermore, exposure to teratogens, such as retinoic acid, cadmium, cyclophosphamide, cocaine and the antiepileptic drug lamotrigine, has been previously reported in association with sirenomelia 3. The patients in this report did not ingest any of these agents.…”

“…These hypotheses are: the vascular steal hypothesis and the defective blastogenesis hypothesis 3. The vascular steal hypothesis suggests the existence of an anomalous vessel impeding proper blood flow to the caudal end of the embryo 6 7.…”

Sirenomelia type VI (sympus apus) in one of dizygotic twins at Chiang Mai University Hospital

“…Sirenomelia is a very rare congenital malformation with an incidence of 0.98–4.2 per 100 000 live births 2–4. Most cases are premature births with a birth weight of less than 2500 g 2. Male-to-female ratio is approximately 3:13 4 and 8–15% of cases are in twins 2 5.…”

“…Most cases are premature births with a birth weight of less than 2500 g 2. Male-to-female ratio is approximately 3:13 4 and 8–15% of cases are in twins 2 5. The characteristics of this condition are a single midline lower limb, sacral and pelvic bone anomalies, absent external genitalia, imperforated anus and renal dysgenesis or agenesis.…”

“…Blood stolen from the lower part of the body results in hypoperfusion and an underdevelopment of multiple organs below. The second hypothesis is defective blastogenesis, which is based on a deficiency of caudal mesoderm, impairing the development of the caudal embryonic body in early gestation 2 7 8…”