Progress toward understanding Robin sequence

Abstract

Robin sequence (RS) a congenital malformation named after the French stomatologist Pierre Robin, consists of the triad of micrognathia, subsequently leading to glossoptosis and varying degrees of upper airway obstruction and feeding problems. In the majority of cases a cleft palate and/or syndrome other malformation is present. RS is a heterogenic congenital disorder, whose treatment involves different caregivers from various disciplines, with different views on the approach, diagnosis, and treatment of RS. Subsequently, this makes the treatment of these patients, sometimes critically ill infants, very challenging. In this thesis, we aim to provide insight into several aspects of RS, mainly regarding diagnostics and treatment, and to facilitate decision-making, counselling of involved caretakers, and managing the expectations of parents, to optimize the care of infants with RS. The birth prevalence of RS was estimated to be 1:5,600live births. The minority (37.7%) of the reviewed patients had isolated RS. Of the non-isolated patients, 14.3% had a chromosome anomaly, 47.1% (n=56) a Mendelian disorder, with Stickler syndrome being the most common (n=27), and in 38.7% (n=46), no detectable cause could be found. Mandibular distraction osteogenesis (MDO) is one of the treatment options for RS infants. We conclude that it is an effective surgical option in the treatment of upper airway obstruction in RS, but the possible effects on developing molars and mandibular outgrowth likely necessitate secondary procedures on the long-term. This factor should be considered when deciding on treatment options and counselling of parents. Regarding other treatment options we think that NPA is a feasible, relatively minor invasive treatment option, which should be incorporated in a treatment algorithm for infants with RS as a primary measure. A cost-analysis study between MDO and tracheostomy reveals that there was a threefold increase in average total costs per patient (both direct and indirect; hospitalization, diagnostics, surgery, homecare and work absenteeism) for tracheostomy and four times as many complications were encountered. Tracheostomy seems only indicated as a surgical option to treat a subglottic problem in infants with RS.RS patients revealed to have significant more feeding difficulties than isolated cleft palate only (iCPO) patients and growth in RS infants was significantly lower compared to iCPO and healthy infants, but not affected by kind of airway management, cleft palate grade or associated disorders. Long-term studies are needed to evaluate the effect of the lower growth on further development of infants with RS. Finally we provide a comprehensive and pragmatic approach to the analysis and treatment of infants with RS, which could serve as useful guidance in other clinics to allow better comparison of results, particularly prospective studies. There is an essential need for an evidence-based management strategy with objective measures to further optimize the treatment of RS patients in the future. We hope this thesis will provide a foundation for the development and refinement of treatment approaches and an impetus for further investigations to increase our knowledge of this challenging patient group.