It has come to the attention of the PMSF Medical Advisory Committee (MAC) that, in rare cases, some individuals with Phelan-McDermid syndrome are also at risk for metachromatic leukodystrophy (MLD) caused by variants in the arylsulfatase A (ARSA) gene and megalencephalic leukoencephalopathy with subcortical cysts (MLC) caused by variants in the MLC1 gene. For this reason, we wanted to provide the following guidance.