TCF4 and microcephaly: Their high expression in NSCs suggested that these transcription factors are relevant for NSC biology and indeed Olig2, Npas3 and Sox2 were shown to be essential for NSC identity.17, 18, 19 On an MD-level, TCF4 haploinsufficiency causes Pitt Hopkins syndrome, which features severe ID, lack of speech, microcephaly and breathing abnormalities.20, 21 Several single-nucleotide polymorphisms in the TCF4 locus are genetic risk factors for developing schizophrenia.4, 22OLIG2 is triploid in Down syndrome patients.