Methylphenidate in KBG Syndrome: N-of-1 Series

The goal of this clinical trial\] is to learn about the effect of methylphenidate in children and adolescents with KBG syndrome. The main question it aims to answer is: • What is the effectiveness of methylphenidate on attention deficit and ADHD-related symptoms in children and adolescents with KBG syndrome? Participants will receive multiple blocks of treatment with methylphenidate and placebo and fill out various questionnaires.

Inclusion Criteria: * Age 6-20 years * Molecularly confirmed diagnosis of KBG syndrome (pathogenic ANKRD11 variant or a chromosome 16q24 deletion including ANKRD11) * Attention deficit or ADHD-related symptoms or a formal ADHD diagnosis, with a significant impact on daily life\* * Presence of a subject's caregiver or supervisor for proxy-reports Exclusion Criteria: * Family history of acute cardiac death that warrants further cardiac investigation * Cardiovascular disease in medical history (severe hypertension, heart failure, arterial occlusive disease, potentially life-threatening arrythmias, angina pectoris, hemodynamically significant congenital heart defect, cardiomyopathy, myocardial infarction and channelopathy) * Current or previous presence of hyperthyroidism, glaucoma or pheochromocytoma * Use of (psychotropic/stimulant) drugs which interact with MPH * Schizophrenic or psychotic disorder in medical history * Unstable epilepsy (not controlled with medication) * History of frequent drug and/or alcohol abuse * Excessive alcohol/drug use and/or intoxication with one or both during the study * Pregnant or lactating women * Inability to understand or speak Dutch