SHANK3 is one of the major genes associated with autism spectrum disorders (ASD) and intellectual disability (ID). The vast majority of the cases who carry heterozygote de novo SHANK3 mutations have ID and >80% also have ASD. Additional clinical traits can co-exist such as epilepsy (25-60%), dysmorphic facial features, motor alteration (hypotonia) and developmental delay. SHANK3 is also deleted in the vast majority of patients diagnosed with Phelan McDermid Syndrome (PMS; OMIM # 606232) patients carrying a deletion of 22q13.
For patients with deletion of SHANK3 due to a ring 22, problems in audition should be investigated since the patients are at risk to develop NF2 associated schwannomas (tumors of the acoustic nerve). It is estimated that 1% of patients with NF2 abnormalities are due to ring 22.
In rare cases, SHANK3 duplications can be observed in patients with hyperkinetic neuropsychiatric disorder, Asperger syndrome, in schizophrenia and bipolar disorders patients. For a review see Guilmatre et al. (2014).