Due to the publicity of the Michael Foundation and the Michael Prize, Michael’s face was known to the international epilepsy community for decades. Renowned epileptologists have been involved in the treatment of Michael’s epilepsy [2] and many more have seen (likely recurrently) Michael’s facial photographs [1]. It appears to be a common phenomenon that with the increasing age of an affected individual and the duration of a non-progressive course, the motivation of the circle of caregivers, physicians, family, and other relatives decreases to search for an etiologic cause of a disorder. Thus, despite the high probability of a genetic etiology of Michael’s disorder, genetic testing was never initiated—neither in the past decades, when basic chromosomal analysis had started to be standard within the diagnostic work-up of individuals with intellectual disability, nor in the recent past, when comprehensive genetic testing methods enabled a diagnostic yield of about 50% of affected individuals [3].

Michael’s unique and specific cognitive profile with strengths in verbal memory and language skills combined with more severely impaired cognitive function in the range of mild intellectual disability is indicative of WBS. This suspicion is further supported by his outgoing personality with a gentle and kind temper. Similar to Michael, height below average as well as microcephaly each occur in 30–50% of individuals with WBS [8]. Lastly, his facial gestalt immediately appeared suggestive of WBS.

However, some clinical anomalies frequently observed in individuals with WBS were not seen in Michael, such as cardiovascular disease, connective tissue abnormalities, and growth as well as endocrine abnormalities. Also, his bitemporal narrowing with broad nasal tip could have been—in part—the physical–morphological expression of administration of phenytoin during the Michael’s growth phase [18].

Epilepsy has frequently been diagnosed in individuals with WBS [9]; however, its exact prevalence in this disorder remains unknown. The spectrum of epileptic seizures observed in WBS comprises focal dyscognitive, focal motor, myoclonic, atonic, tonic, generalized tonic–clonic, seizures, and epileptic spasms [9,10,11]. In some individuals, epilepsy was explicitly described as refractory [11, 12]. However, in at least one case, this was assigned to a second underlying genetic disease [11]. Thus, Michael’s refractory epilepsy appears compatible with WBS, although it may not necessarily have had the same etiology as his remaining phenotype.

Williams–Beuren syndrome belongs to the class of syndromes with a highly characteristic facial gestalt, and the positive likelihood ratio for correctly recognizing this disorder in an actual case is over 90%. Since age can be a confounder in the analysis, the best results are obtained if comparisons can be made with multiple images showing the individual at different ages. For Michael, three portraits were analyzed and gestalt scores consistently showed WBS as the likeliest diagnosis.

Michael’s symptoms, particularly his specific cognitive profile as well as his facial dysmorphic features, analyzed both by the human eye and artificial intelligence therefore establish WBS as the most likely clinical diagnosis by far.

Would an earlier diagnosis of WBS have made any difference to Michael or his family, relatives, or caregivers? The answer to this question is complex.

Yes, it would have made a difference in taking care of Michael. Recommended evaluations following the diagnosis of WBS comprise (a) screening for behavioral concerns, including attention, anxiety, and sleep disorders; (b) cardiovascular imaging; (c) assessment of reduced vision, hearing loss, and dental anomalies; (d) checking for hypercalcemia; and (e) thyroid function tests [8]. As Michael did not have relevant clinical problems in these areas (or it was already taken care of, e.g., myopia), he apparently did not require specific medical care. However, caregivers would generally have been better prepared if a diagnosis of WBS had been known earlier, even if Michael’s individual treatment would likely have stayed unchanged. No particular recommendations exist to treat epilepsy in WBS.

Yes, it would have made a difference to the family, particularly to his parents. Obviously, even after 80 years and long after the death of both parents, an exogenic cause (fall from baby scales) was considered a possible etiologic explanation for Michael’s disorder [2]. Knowledge of an inborn genetic disorder may have relieved the parents from a potential feeling of guilt. Furthermore, the anticipated potential proof of a de novo origin of a common WBS-associated microdeletion on 7q11.23 would have allowed for counseling of the family on inheritance and recurrence risks.

Yes, it would have made a difference in the perception of his disorder. Michael would perhaps have been recognized as an individual with WBS with refractory epilepsy rather than an individual with primarily refractory epilepsy whose unique but specific additional symptoms remained disregarded or perhaps attributed to being a consequence of his epilepsy and not being a complex genetic disorder. It, furthermore, would have helped to shed light on the usually barely understood late and geriatric course of an otherwise well-known genetic disorder.

Thus, genetic testing of older individuals is helpful not solely for the affected individuals themselves, but also because a clear diagnosis may help in the individualization of care, in establishing precision medicine approaches, and last but not least in guiding families and providing knowledge on the course and the inheritance pattern of the respective disorder [3, 4, 13,14,15,16]. Michael’s case should remind us that we should never overlook the search for an underlying diagnosis.