Subsequent late diagnosis of ASD after an initial ASD-negative comprehensive assessment is a common clinical experience. Reasons for this scenario may include evolving diagnosis as well as missed and overdiagnosed cases of ASD.

We speculate that in neuronal cells, impairment of fusion of the late endosome to the vacuole would attenuate the degradation of plasma membrane receptors, thereby underlying the progressive neuronal phenotype in our patients. The VPS11 p.Cys846Gly mutation should be added to the AJ carrier screening panel.

The prevalence of macrocephaly in autism spectrum disorder is reported to be much higher than in the general population, 12% to 37%. Progressive macrocephaly is even considered a warning sign for the development of autism. We evaluated the prevalence of an abnormal head circumference in children with autism in Israel and compared it with the head circumferences of children with developmental language disorder and children with normal development. We did not find a higher prevalence of macrocephaly among Israeli children with autism spectrum disorder (4.4%). Although children with autism spectrum disorder had a significantly higher rate of a head circumference above the 75th percentile compared with children with developmental language disorder, it was not significantly different compared with normal controls. We conclude that there is no increased prevalence of macrocephaly in Israeli children with autism; this can be attributed to a different genetic background.