Using NGS, in only five years more than eighty genes were related to the RTT-like phenotype and some of these genes were identified as causative for aRTT or RTT-like phenotype in these patients, although some of them were associated with well-known syndromes such as Pitt–Hopkins syndrome (TCF4, CNTNAP2 and NRXN1 genes), Phelan–McDermid syndrome (SHANK3 gene), Angelman syndrome (UBE3A gene), Kleefstra syndrome (EHMT1) and Cornelia de Lange syndrome (SMC1A). The gene discussed is SHANK3; the disease is Kleefstra syndrome.