We identified three rare heterozygous likely damaging coding variants in MECP2 in five girls: a de novo missense variant (p.Arg97Cys) in two monozygotic twin sisters with CPP and microcephaly; a de novo missense variant (p.Ser176Arg) in one girl with sporadic CPP, obesity and autism; and an insertion (p.Ala6_Ala8dup) in two unrelated girls with sporadic CPP. The gene discussed is MECP2; the disease is obesity due to melanocortin 4 receptor deficiency.