Page 213 - Demo

General discussion and future perspectives2118and otolaryngologic examinations are part of standard routine care at the 22q11.2 expert clinic at Maastricht University Medical Center. Only a minority of adults were examined upon indication for (suspicion of) ophthalmic, otolaryngologic or movement disorders. Limitations mainly related to the retrospective or cross-sectional design of most studies. Data concerning the medical history may not be complete resulting in an underestimation of the studied conditions. In some cases, patients that were examined were noncooperative or had difficulties with performing tasks, which most likely concerned individuals with a more severe phenotype, that may have resulted in a slight underestimation of the prevalence rates of studied conditions. However, referral bias may have resulted in higher prevalence rates because individuals with 22q11.2DS with a more severe phenotype may have higher probabilities of being referred to a 22q11 specialty clinic. Age of onset of conditions such as hearing loss, refractive errors or sleep apnea was often not reported in the medical files, and was therefore not subject of study. This hampers the ability to differentiate between manifestations with early- or adult-onset, which is important information for the improvement of screening recommendations. In addition, the average age of the study participants in most studies was still quite young. Because most conditions may increase with age, this will have resulted in an underestimation of prevalence rates of late-onset conditions.Comparisons of studied conditions with previous studies was often complicated due to the use of different definitions, cut-off values and measurement techniques or because other studies did not distinguish findings in children from findings in adults.63-65The systematic literature review, described in chapter 2, had some specific limitations of which the most important one relates to the definition that was used for a GND. Inclusion of all conditions listed in HPO as “neurodevelopmental abnormality”, in addition to the large number and wide spectrum of genetically and clinically heterogeneous disorders and the absence of a perfect classification system, may have resulted in the inclusion of conditions that should not be considered to affect brain development.