Discussion

CHDs have been reported in several patients with fetal valproat syndrome, and the incidence of CHD is estimated to be around four times that seen in the general population. ^{Reference Clayton-Smith and Donnai4} In some case series, septal defects and valvular diseases have been reported with extremity anomalies. Some features of these anomalies, including radius aplasia, clinodactyly, and contracture of wrists have been reported similar to Holt–Oram syndrome, Fanconia anaemia, and thrombocytopenia absent radii in fetal valproat syndrome. ^{Reference Mohd and Green1,Reference Mutlu-Albayrak, Bulut and Çaksen5,Reference Shimamura and Alter6} The facial findings of fetal valproat syndrome include hypertelorism, frontal bossing, flat nasal bridge, broad forehead, anteverted nares, midface hypoplasia, bitemporal narrowing, posteriorly rotated ears, thin lips, and long philtrum. ^{Reference Williams, King, Cunningham, Stephan, Kerr and Hersh7} Holt–Oram syndrome is an autosomal dominant disease characterised by various cardiac anomalies, including clinodactyly, absence of thumb, hypoplasia or agenesis of the radius, ulna hypoplasia, carpal bone anomalies, and atrial septal defect. ^{Reference Mori and Bruneau8} In addition, Fanconi anaemia has similar clinical skeletal and cardiac abnormalities, but it is autosomal recessive disease and skin findings including hyper- or hypopigmentation or café-au-lait spots reported to be frequent. Eye malformations including strabismus and hypo/hypertelorism also reported and individuals do not develop bone marrow failure early in their course. Patients with thrombocytopenia absent radii present as newborns with thrombocytopenia and characteristic physical findings of bilateral absent radii (unilateral in about 2% of cases) with thumbs present albeit abnormal in appearance. ^{Reference Shimamura and Alter6} In our case, clinical features of extremity and cardiac findings were observed similar to Holt–Oram syndrome and Fanconia anaemia, but there was no family history of disease and consanguinity between the parents. Patient’s whole blood count was normal that ruled out thrombocytopenia absent radii. Skin manifestations including hyper- or hypopigmentation or café-au-lait spots were not seen in our patient contrary to frequently seen in Fanconia patients. Also, any mutation was not found in favour of Holt–Oram syndrome and Fanconi anaemia in clinical exome sequencing test. Chromosome analysis excluded trisomy disorders. In addition, the presence of typical facial anomalies, sacral hypertrichosis, spina bifida, exposure to valproic acid in both pregnancies and the history of autism in her sibling suggest that diagnose is fetal valproate syndrome. Our case is the first case in the literature in which fetal valproate syndrome is accompanied by a coronary AV fistula. Coronary AV fistula before reported in Down syndrome and Klinefelter syndrome but it is firstly reported in our case with teratogenicity. ^{Reference La Placa, Pinello, Schierz, Giuffrè and Corsello9,Reference Yoshida, Ryu and Ogata10} The coronary AV fistula of the patient was treated with percutaneous transcatheter closure and he was discharged from our centre.