Sirenomelia with alveolar capillary dysplasia: An unusual association

Dear Editor,

A 24-year-old primigravida female conceived monochorionic diamniotic twins following a cycle of ovulation induction with clomiphene citrate. There was no history of consanguinity. The antenatal period was otherwise uneventful. An anomaly scan performed at 22 weeks of gestation at another center was unremarkable. Gross weight discordance (56%) was noted between both the twins, twin I and twin II at the third-trimester growth scan. Emergency cesarean section was done at 35 weeks of gestation because of severe fetal growth restriction and fetal bradycardia in twin II. Grossly discordant twins were born 2 min apart with birthweights, 2520 g and 820 g, respectively. Twin I was a vigorous male baby with a smooth perinatal transition. Twin II had gross anomalies, and due to the absence of external genital organs, a clear gender could not be assigned and was labeled ambiguous at admission. Weak cries and poor respiratory efforts were noted immediately following delivery. Immediate cord clamping was done, and the baby was resuscitated with positive pressure ventilation. Delivery room CPAP support was initiated for respiratory distress. The baby was subsequently shifted to NICU.

During the initial evaluation, the baby had a solitary tapering axially rotated lower limb ending in a single toe, single umbilical artery, absent external genitalia and urethral opening, and imperforate anus. A rudimentary tail-like structure was seen posteriorly in the lumbosacral region (Fig. 1). There was no facial dysmorphism. The type VI variant of Stocker et al, classification (single femur and tibia) was established on the babygram.¹ Sacral vertebral agenesis was also noted. Ultrasound abdomen showed bilateral renal agenesis without a renal collecting system and urinary bladder. Since bilateral renal agenesis is incompatible with life, surgical options like urinary diversion procedures were not explored. The parents were counseled about the disease condition, associated anomalies, and consequences. They opted for compassionate care. In the absence of ureteral orifice, fluid management was challenging. The baby was given restricted fluids with a glucose infusion rate of 4 mg/kg/min. The baby remained on respiratory support until its demise on the fifth postnatal day. At autopsy, additional findings noted were mal-positioned pulmonary vasculature findings noted were alveolar capillary dysplasia with misalignment of pulmonary veins justifying the requirement for respiratory support following birth (Fig. 2). The large intestine terminated in a blind pouch. No gonads were identified. The karyotype was suggestive of a male with 46XY chromosomes. Patient/parent informed consent was obtained for use of figures in the study.

Fig. 1.

Clinical images showing a single axially rotated tapering lower limb ending in a single toe with tail-like projection in the sacrococcygeal region with imperforate anus.

Fig. 2.

Alveolar capillary dysplasia with misalignment of pulmonary veins. (i) Broad alveolar septa (H&E, 40X). (ii) Pulmonary venous branches (v), adjacent to pulmonary arteries (a) and bronchiole (b) (the branch of the pulmonary vein shares same adventitial sheath with the branch of the pulmonary artery).

The sirenomelia sequence is characterized by variable degrees of lower limb fusion. The prevalence is 0.98 per 100,000 live births worldwide.² The incidence in monozygotic twins is almost 100 folds that of singleton births and dizygotic twin pregnancies. This striking phenotypic gestalt is often associated with various visceral abnormalities, most commonly gastrointestinal and urogenital anomalies. The presence of associated congenital anomalies involving vital organs govern the prognosis for morbidity, survival, and quality of life. More than half of reported cases of sirenomelia are stillborn, and those born alive usually die before the 5th postnatal day.² Because of overlapping features, many authors often consider sirenomelia as the extreme form of caudal regression syndrome and the VACTERL spectrum. Stocker and Heifetz classified sirenomelia into seven types based on the degree of fusion skeletal elements in the lower limbs. Type I is the mildest form involving the fusion of superficial tissues with all bones intact in the two fused limbs. In contrast, only single femur is present while, tibia is absent in type VII.

The triggering factor in the initiation of this sequence is not entirely understood. According to the “vascular steal hypothesis,” an aberrant abdominal artery arises from a higher level of the aorta without renal or iliac artery branches, thus, carrying most of the blood to the placenta. As a result, the caudal mesoderm is devoid of adequate blood flow and nutrient supply resulting in agenesis of the midline structures and atypical fusion of the lower limbs. According to the “defective blastogenesis” theory, teratogenic exposure during the gastrulation phase results in defective evolution of the caudal mesoderm. Maternal diabetes, retinoic acid, and tobacco use are a few known environmental factors.³ Our index case was the second of the monozygotic twins conceived through ovulation induction. The parents were counseled about the guarded prognosis in the presence of accompanying life-threatening abnormalities (bilateral renal agenesis and absence of the renal collecting system) with a severe grade of limb fusion. They eventually opted for compassionate care. The most common respiratory abnormality noted in sirenomelia is pulmonary hypoplasia. However, the requirement for respiratory support in our case was attributed to alveolar capillary dysplasia with the misalignment of pulmonary veins (ACD-MVP) based on autopsy findings. This association has never been reported previously. It adds to the ever-expanding spectrum of lethal abnormalities related to sirenomelia.

ACD-MVP results from the premature arrest of lung growth and is characterized by poorly developed pulmonary lobules with reduced capillary density.⁴ The disorganized development of alveoli and distal airspaces contribute to early-onset respiratory failure with refractory hypoxemia. It is almost 100% fatal.⁵ Previous studies have reported extrapulmonary findings in 50–80% of the cases.^4,6 A baby with unexplained respiratory failure with associated structural anomalies involving the genitourinary, gastrointestinal, or cardiovascular system should raise suspicion of ACD-MPV.

In the presence of multiple congenital anomalies, the quality of life and survival in live-born sirenomelia is dismal. It is often fatal in the perinatal period. Therefore, timely antenatal diagnosis is essential. The presence of a single lower extremity in early pregnancy may clinch the diagnosis and aid in informed decision-making. However, identification may become progressively difficult with advancing gestation and worsening oligohydramnios. In the index case, the antenatal diagnosis was missed in the backdrop of multiple gestation. A multidisciplinary team must be instituted to counsel the expecting parents about the anticipated complications and consequent management. Voluntary selective termination of the sirenomelia twin may be advised to the parents, guided by local law and ethical considerations.

Patients/ Guardians/ Participants consent

Patients informed consent was obtained.

Ethical clearance

Not Applicable.

Source of support

Nil.

Disclosure of competing interest

The authors have none to declare.