Parents

PMS associated with 22q13.3 deletion occurred mostly de novo and are diagnosed using microarray. 22q13.3 deletion should always be validated by conventional cytogenetic testing in order to eliminate a ring 22. Indeed patients with ring 22 should have more stringent monitoring.SHANK3 mutations which are associated with intellectual disability and autism spectrum disorders (ASD) are in majority heterozygous and de novo. ASD are neurodevelopmental disorders characterized by impairments in social interactions as well as the manifestation of repetitive behaviors and restricted interests. A meta-analysis found that 1-2% of patients with ASD and ID are carrying a de novo SHANK3 mutation/deletions. The majority of the cases are carrying large to small deletions of 22q13 or SHANK3 mutations and are diagnosed with Phelan McDermid Syndrome (PMS; OMIM# 606232). They all have ID and in >80% also have ASD. Additional clinical traits can co-exist such as epilepsy (25-60%), dysmorphic facial features, motor alteration (hypotonia in 75%) and developmental delay.