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Reply: Treacher Collins Syndrome: A Systematic Review of Evidence-Based Treatment and Recommendations.

Reply: Treacher collins Syndrome: A Systematic Review of Evidence-Based Treatment and Recommendations Sir: First of all, we would like to thank Herlin and colleagues for their interest and constructive comments regarding our article and treatment algorithm. Until now, no reviews or guidelines were available on evidence-based treatment of Treacher Collins syndrome. Thus, a first systematic attempt was undertaken covering several clinical implications of this rare congenital craniofacial syndrome. We set out to perform an evidencebased review. However, the available literature limited us from achieving this goal, as the level of evidence found is much lower than we hoped for. Herlin and colleagues propose to pool the data of the studies. However, data regarding the 63 included studies were very heterogeneous, used several inclusion criteria, were mainly retrospective, considered sometimes several clinical topics and, although we used strict inclusion criteria in the systematic search, only levels of evidence II through V were found. In our opinion, relatively “large” studies may still suffer from selection bias. Thus, describing simple averages of pooled data of mainly descriptive statistics, other than the averages mentioned in the Results, would not have been of an added value. Altogether, pooling data would not result in a higher level of evidence or a higher grade of recommendation. Although Herlin and colleagues emphasize the importance of expert opinions, we think that we need all levels of evidence, including level V, to draw conclusions in evidence-based medicine.1 The authors state that we did not include a relatively large study in March of 2015, which was the result of our inclusion period for the systematic search that ended. Regarding obstructive sleep apnea, these studies indeed dealt with a heterogeneous number of patients, with five of the 10 studies having evidence level II. This is one of the relatively best evidence-based items. The inverse relationship between the degree of resorption of calvarial bone grafts for zygomatic reconstruction in Treacher Collins syndrome and increasing age is indeed a relevant finding reported by Fan et al.2 This systematic review highlights the many uncertainties there still are concerning treatment of patients with Treacher Collins syndrome. Gaining reliable data on treatment and outcome will require intercenter studies. The initiative of the European Commission to start European reference networks on rare diseases may be an important first step in achieving this goal. DOI: 10.1097/PRS.0000000000002382