Congenital anomalies and etiological diversity in autism

Abstract

from vigabatrin-related retinal toxicity. Riikonen et al.'s results are in favour of a relationship between exposure and toxicity, despite the lack of definite statistical evidence. The authors logically conclude that 'low doses and short treatment' should be used for vigabatrin. Indeed, vigabatrin should be stopped in the case of incomplete control of epilepsy, the reasonable aim for the treatment of infantile spasms.However, these suggestions require some precision to be applied in clinical practice. The first pitfall would be to discourage vigabatrin prescription in newly diagnosed infantile spasms. To date no other drug proved to be efficient on symptomatic epileptic spasms except hormonal therapy at high doses, which demonstrated lower efficacy than vigabatrin in tuberous sclerosis 1 and equivalent efficacy at 1 year in other causes.5 Potentially life-threatening adverse events of steroids have also to be considered when compared to vigabatrin retinal toxicity. Finally, the subjective impact of vigabatrin-related VFL is exceptionally assessed in the reports: in fact very few patients complain of such peripheral VFL. Except for driving, VFL seldom alters quality of life, and in no case would the impact be comparable to the cognitive deterioration caused by persisting or relapsing infantile spasms.The second pitfall would be to underestimate the required vigabatrin dose <36mg/kg/day proved to be inefficient randomly compared to the usual 100-150mg/kg/day, 6 and the lowest effective dose has yet to be determined. Interestingly, the daily dose of vigabatrin was found positively correlated to the severity of VFL: in Riikonen et al.'s study five of the nine patients receiving at least 1500mg/ day provided five of the six severe VFL cases.The third and still unsolved question is the optimal treatment duration regarding the risk of relapse of refractory infantile spasms and cognitive deterioration after vigabatrin termination. Infantile spasms relapse is maximum within the first year of treatment, but may occasionally occur some years later after vigabatrin withdrawal and be untreatable, particularly in focal cortical dysplasia and tuberous sclerosis. 7 In other cases, it seems possible not to exceed 6 months' treatment.The risk of vigabatrin needs, therefore, to be balanced against that of alternative therapy and of the disease, including severe relapse determined by aetiology. Leo Kanner, in his original case series 1 that introduced the diagnostic concept of autism, observed that children with the behavioral syndrome were essentially healthy and without abnormalities in physical morphology, apart from an enlarged head size in some. However, with subsequent attention to the importance of neurobiological factors in the etiology of autism, an association with congenital anomalies was recognized.2 As TimonenSoivio et al. report, 3 population-based studies over the past 15 years have consistently detected an increased rate of congenital anomalies among children with autism spectrum disorder (ASD). However, important...