PTEN associated Macrocephaly/Autism Syndrome

Autism spectrum disorders (ASDs) are a group of severe neurodevelopmental disorders, in which patients show deficits in social interaction, impaired communication, repetitive behavior and restricted interests and activities. The prevalence of ASDs is rising, and it is estimated that 60 per 10,000 individuals currently have a form of ASD and 13 per 10,000 individuals have autism. ASDs include several clinically defined conditions, of which pervasive developmental disorder (not otherwise specified) and autistic disorder (‘classic’ autism) are the most common. Autism often appears to be associated with either macrocephaly or microcephaly. It is reported that 83% of patients with autism have a head circumference greater than the 50th percentile, and 24% have a head circumference above the 98th percentile. Mutations in the PTEN gene have been reported in a subgroup of patients with ASD who had significant macrocephaly with a head circumferences ranging from +2.5 to +8 SD for age and sex. Most but not all patients also had dysmorphic features, such as broad forehead, hypertelorism, midface hypoplasia, depressed nasal bridge, long philtrum and short nose. However, typical clinical features of Cowden syndrome (CS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS) were usually lacking.