**1. Introduction**

Sirenomelia (SML) is a rare and almost universally fatal congenital malformation characterized by the pathognomonic feature of fused lower extremities, with absent or malformed perineum and Potter facies (**Figure 1**) [1]. SML, also called mermaid syndrome, is one of the most striking phenotypes among human anomalies. The exact etiopathogenesis of SML is undetermined, and the syndrome is postulated to be due to a genetic predisposition that is unmasked by a biochemical or environmental trigger factor. Several hypotheses have been proposed for the pathogenesis, among which the most accepted ones are vascular steal phenomenon, defective blastogenesis, and mechanical compression of the fetal caudal body. [1–8] Studies in mutant mice have provided significant and relevant information towards the understanding

**Figure 1.** *Sirenomelia in a newborn infant showing merged hind extremities and Potter facies.*

of the genetic aspect of the anomaly. [1] SML occurs sporadically, and even though not recognized as familial, it is documented to be more common in twin monozygotic pregnancies, among whom the relative risk is stated to be increased by 100-fold. About 9–15% of all cases of SML are products of twin gestation. Environmental and teratogenic factors, such as cocaine, retinoic acid, heavy metals, cyclophosphamide, and certain antibiotics, have been linked to SML in humans and animal models [1, 9]. In addition, nicotine, alcohol, radionuclides, diethylpropion- an appetite suppressor, organic solvents of fats, and even air pollution have been associated with SML and caudal regression syndrome, which is controversially considered as its minor form [4, 9]. Other authors have reported fetal exposure to cadmium, lithium, phenytoin, sodium valproate, carbamazepine, warfarin, methylergonovine, diethylpropion, trimethoprim, and ochratoxin-a type of fungus as possible triggers for the anomaly. [7–9] Some of the maternal complications, such as diabetes mellitus, hyperthermia during the 1st trimester of pregnancy, amniotic bands, and age below 20 years or over 40 years at conception, have also been implicated in the pathogenesis of SML. [1, 9]. Recently a case report tentatively associated persistent early gestational maternal Chlamydia trachomatis (CT) infection with SML. CT is an obligate intracellular pathogen that is recognized for its cytopathogenic effects like cellular disruption, tissue dysgenesis, and genomic instability and is known to invade the placenta and cause fetal demise. [10] SML has no ethnic or geographical preferences, and a gender preponderance with a male to female ratio of 2.7:1 has been described. [1] The prevalence of SML is reported to be between 1.1 and 4.2 per 100,000 births [1, 6]. The molecular basis of the defects in SML is yet to be defined.
