Given the reasonable safety profile of trametinib and the significant disability complex vascular malformations can cause in paediatric patients, five patients (including two with SAMS) with identified somatic mosaic variants in the RAS-MEK pathway (Patients 1, 2, 3, 6, and 10) have been commenced on genotype-directed pharmacotherapy, with approval by the pharmaceutical companies on compassionate grounds. The gene discussed is MAP2K7; the disease is short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome.