In order to prove with certainty that the CELSR3 does not contribute to cause the EE pathogenesis, further patients should be recruited that do show mutations in CACNA2D2 but not in CELSR3. However, it is often difficult to recruit additional patients or families with an ultra-rare disorder such as the one affecting the present proband. The gene discussed is CACNA2D2; the disease is ethylmalonic encephalopathy.