Clinical Characteristics

SHANK3 is one of the major genes associated with autism spectrum disorders (ASD) and intellectual disability (ID). 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.
In rare cases, SHANK3 duplications can be observed in patients with hyperkinetic neuropsychiatric disorder, Asperger syndrome, schizophrenia and bipolar disorders. For a review see Guilmatre et al. (2014).