Tibial Agenesis and Gollop-Wolfgang Complex in Three Siblings Born to an Epileptic Woman Treated with Carbamazepine: Teratogenicity?

The term “limb deficiency” incorporates absence and/or size reduction of any of the 120 human limb bones, with around 205 identified nosologic entities. Of these, the GollopWolfgang Complex (GWC) is a rare abnormality comprising absence of tibia and ipsilateral forked femur with ectrodactyly. There is scarcity of literature implicating antiepileptic drugs in the etiology of GWC but the teratogenecity of antiepileptics especially valproate is well documented. The management of epilepsy during pregnancy requires a balance between control, the risks involved in uncontrolled seizures and the teratogenecity of antiepileptic drugs. This study presents three siblings with GWC and tibial agenesis whose epileptic mother had been on treatment with carbamazepine for 10 years. To the author’s knowledge, this is the first time that carbamazepine has been implicated in causation of GWC/tibial agenesis. *Corresponding author: Nasir Muzaffar, Bone and Joint Surgery Hospital, Barzalla, Srinagar, Kashmir, J&K, India; Pin190005, Tel: 91-0194-2430155/2430149, 919858812593; Fax: 91-0194-2433730; E-mail: [email protected] Received September 04, 2013; Accepted September 05, 2013; Published September 10, 2013 Citation: Muzaffar N (2013) Tibial Agenesis and Gollop-Wolfgang Complex in Three Siblings Born to an Epileptic Woman Treated with Carbamazepine: Teratogenicity? Genetics 2: 118. doi:10.4172/2161-1041.1000118 Copyright: © 2013 Muzaffar N. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction Gollop-Wolfgang Complex (GWC) is a rare congenital limb anomaly characterized by tibial aplasia, ipsilateral bifurcation of the thighbone and an ectrodactyly [1]. It is often associated with other anomalies of limbs, heart, digestive and urinary tracts and the lumbosacral vertebrae [2,3]. Congenital absence of tibia is a rare and severe lower limb malformation with an incidence of approximately 1:1,000,000 live births [4,5]. Anomalies like Tibial hemimelia with split hand/foot malformation (TH-SHFM) and Gollop-Wolfgang complex6 are rarer malformations with highly variable manifestations. The first case with this pattern of malformations may have been reported by Sir Ambroise Pare in 1575 [6]. GWC is a form of tibial field defect, which includes distal femoral bifurcation, tibial agenesis, oligo-ectrodactylous toe defects or preaxial polydactyly, occasionally associated with hand ectrodactyly. The etiology of GWC is still unclear [7]. This study presents three siblings suffering with GWC whose mother had been treated with carbamazepine for more than decade for grand mal epilepsy. There was no history of any skeletal deformity in both parents’ families prior to these three sibs. Clinical Report Patient 1 The first born child (a girl) of a 32 year old mother without malformations, with normal karyotype (46 XX) had GWC. There was no documented consanguinity with the father, no similar family history, no history of radiation exposure; the mother was a grand mal epileptic and had been taking carbamazepine without folate supplementation prior to and during pregnancy. The child had bifurcated left distal femur with right tibial agenesis, plus right knee subluxation, clubfoot and hypoplasia of the first ray of the right foot (Figure 1). She could sit without help but it was impossible for her to stand upright without support because of functional disability of the right lower limb. At the medial distal third of the left femur, a large bony protuberance was present having a width of 13 cm and a length of 5 cm. The patella was not palpable. The right leg was thinner and shorter than the left. There was no visible medial malleolus. The right foot was in varus equinus position. Radiograph of the left lower limb (Figure 2) showed a bifurcation of the distal 1/3 of the femur and on the right, agenesis of the patella, tibia, astragalus and first metatarsal.