A rare occurrence of concordant neural tube defects in monozygotic twins of an epileptic woman

Tella Sunitha¹, Rebekah Prasoona¹, Anjana Munshi¹, Madireddi Sujatha¹, Turaga Surya Prabha², Akka Jyothy¹,  
¹ Department of Clinical Genetics, Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, India
² Department of Neurology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India

Correspondence Address:
Akka Jyothy
Department of Clinical Genetics, Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet
India

Full Text

Sir,

A 28-year-old woman with epilepsy (WWE), primi gravida was referred for prenatal scan at 25 weeks of gestation. Last menstrual period was confirmed by ultrasound and she had conceived pregnancy naturally. She had no positive family history of stillbirths, neural tube defects and other congenital anomalies. There was no history of consanguinity [Figure 1]. For the epilepsy (complex partial seizures) she had been on valproate (2000 mg/ day) since five years and folic acid was added pre-conceptionally. She continued to take valproate and folic acid (5 mg/day) during the entire period of pregnancy. In addition, she had also been on calcium and multivitamin supplements. Ultrasound scan of the proband revealed twin gestation which was found to be monochorionic diamniotic, i.e. monozygotic based on the absence of 'twin peak' sign. Both the twins shared a single placenta and the placentation was posterior. Twin A was breech in presentation weighing 667 ± 97 g and showed occipital encephalocele measuring 3 cm Χ 2 cm [Figure 2] and [Figure 3]. Twin B was cephalic in presentation weighing 838 ± 122 g and showed sacrococcygeal meningocele measuring 3 cm Χ 8 cm. The sonographic findings were also confirmed postnatally. On examining the babies after delivery they did not seem to have any other malformations. However, we could not do any computed tomography scan or magnetic resonance imaging to confirm the malformations which were not visible externally. The case was investigated with her informed written consent and had the institutional ethics committee approval.{Figure 1}{Figure 2}{Figure 3}

Neural tube defects (NTDs) are a group of congenital malformations with a worldwide incidence of 0.5-2/1000 pregnancies [1] and are the most common major anomalies associated with in utero exposure to antiepileptic drugs (AEDs). [2] However, NTDs affecting both fetuses in a twin pregnancy are very rare. A multitude of environmental factors have been implicated in the pathogenesis of NTDs such as ethnicity, season of conception, socioeconomic class, nutritional status (zinc and folic acid deficiency), maternal diabetes, alcohol abuse or elevated maternal temperature during the first month of gestation, and maternal use of drugs. [3] AED exposure in utero poses a risk of congenital malformations to the child. [4] However, valproate use has been associated especially with lumbosacral meningocele rather than other forms of NTD such as anencephaly. [5] The present study also observed that one of the twins was affected with sacrococcygeal meningocele suggesting the effect of valproate in the closure site 5 (the lumbosacral region). To the best of our knowledge this is the first report showing concordant NTDs in monozygotic twins of a WWE exposed to valproic acid.

It has been reported that neuroparalytic complications of the prenatally diagnosed cases are less if they are delivered by cesarean section. Cesarean section at term is performed to prevent birth trauma to the exposed spinal cord. [6] Prenatal or intrauterine repair of NTDs, especially myelomeningocele is an acceptable fetal surgery. This is being investigated in the Management of Myelomeningocele Study (MOMS) trial, a controlled clinical trial of 200 patients in three institutions. [7] The findings in our patient strongly suggest the importance of comprehensive care of WWE which includes preconceptional counseling, most effective folic acid supplementation prior to conception, substitution of valproate by a safer AED and a thorough follow-up which are crucial during gestation to prevent the occurrence of NTDs. It is also important to provide extensive counseling to WWE in the preconception period as well as through the pregnancy.

 Acknowledgment

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