Page 60 - Demo

Chapter 358IntroductionSmith–Magenis syndrome (SMS) is a rare genetic neurodevelopmental disorder with an estimated prevalence of 1:15.000–25.000 births.1 SMS is caused by a deletion on chromosome 17 (17p11.2) or a pathogenic mutation in the RAI1 gene located within this region. Most of the SMS manifestations are due to haploinsufficiency of RAI1 and thought to be modified by other genes in the 17p11.2 region.2,3,4 Manifestations are variable and include intellectual disability (ID), severe sleep disturbances and psychiatric comorbidity such as autism spectrum disorders (ASD), attention-deficit-hyperactivity disorder (ADHD).5,6,7 Typical behavioural manifestations include problems with emotion dysregulation, self-injurious behaviour and aggressive or stereotypical behaviour, posing a great burden on patients and caregivers.8Treatment of the behavioural manifestations in SMS is complex due to the genetic heterogeneity, clinical variability and severity of symptoms.4,9Traditionally, treatment is focused on appropriate management of sleeping pattern, concomitant somatic comorbidities, psycho-education and professional guidance for parents and caregivers aimed at symptom reduction and optimizing quality of life of both the patient and their family.10,11,12,13 Often, this does not suffice, resulting in the prescription of psychotropic drugs in the vast majority of children and adults with SMS, including stimulants, antidepressants, antipsychotics, mood stabilizers, alfa2 agonists, sleep aids, and benzodiazepines.14For idiopathic ADHD, methylphenidate (MPH) is well-established as first-line treatment with high efficacy and tolerability compared to other psychotropic drugs.15,16,17 However, for ADHD in genetic neurodevelopmental disorders such as SMS more information is necessary as there is increasing evidence for differential treatment response and tolerability.14,18,19 Also, polypharmacy is a clinical pitfall in patients with complex psychiatric disorders and ID, leading to iatrogenic comorbidity.20 Therefore, disorder-specific studies are needed to provide information about the effectiveness of MPH for ADHD. Considering the heterogeneity of the patient population and need for relevancy of interventions, personalized outcome measures are needed to Annelieke Muller sHL.indd 58 14-11-2023 09:07