Abstracts

Rationale: Severe congenital variant of Rett Syndrome is characterizedby loss of muscle tone, microcephaly, stereotypies and lack of purposeful hand development. Mutations in FOXG1 and CDKL5 genes cause early infantile encephalopathies and may lead to a severe atypical Rett syndrome phenotype. We report our experience with 3 infants with early infantile epileptic encephalopathy who developed a phenotype overlapping the severe congenital variant of Rett syndrome. Methods: Patient with history of HIE, congenital or acquired CNS infection, metabolic encephalopathy or CNS malformation were excluded. A comprehensive epilepsy panel was performed in infants with early infantile epileptic encephalopathy who developed a severe atypical Rett syndrome phenotype. Results: Three patients (2 boys, 1 girl), with early infantile epileptic encephalopathy and hypotonia developed a severe atypical Rett syndrome phenotype. Seizures were refractory to most antiepileptic drugs. Microcephaly was progressive and severe in all three patients. Acquisition of purposeful hand development was only achieved transiently in a boy with de novo heterozygous frame shift mutation in FOXG1 gene. The other boy with the KCNT1 mutational hot spot (p.ALA934THR) and a girl with de novo c. 131 C>T mutation in the GNAO1 gene never acquire purposeful hand movements. Bruxism was seen in all three children. All three patients required gavage feeding. Hand wringing stereotypies were noted in all 3 patients. All three patients eventually displayed frequent erratic, poorly coordinated and choreoathetoid movements. Conclusions: A severe atypical Rett syndrome phenotype is possibly a frequent outcome in children with early infantile epileptic encephalopathy. Further prospective studies are needed to evaluate genetic disorders leading to the coexistence of both syndromes. Funding: No funding