patient’s macrocephaly and symptom severity. The finding that altered gene expression does not correlate with HC in the unaffected fathers, despite the fathers having the same degree of macrocephaly, suggests that the macrocephaly in the fathers and in the probands are not equivalent, and that additional genetic factors may control the head size phenotype in ASD. Some studies also detected a different pattern of brain enlargement between patients with ASD and controls (Piven et al., 1996). Although the small number of participants precludes a definitive conclusion, our data indicate that the alterations in the dynamics of brain growth and differentiation discovered using the organoid model represent a core feature of the disorder, rather than an incidental finding, and that dysregulated gene expression in iPSC-derived organoids, and FOXG1 in particular, could be used as potential biomarkers of severe ASD.
