CDKL5 gene related epileptic encephalopathy in Estonia: a case presentation Klari Noormets 1,2, Katrin Õunap 2,3, Ulvi Vaher 1, Tiina Talvik 1,2, Inga Talvik 1,2 1 Children’s Clinic of Tartu University Hospital; 2 University of Tartu, Department of Pediatrics; 3 Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia. CDKL5 gene related epileptic encephalopathy in Estonia: a case presentation Klari Noormets 1,2, Katrin Õunap 2,3, Ulvi Vaher 1, Tiina Talvik 1,2, Inga Talvik 1,2 1 Children’s Clinic of Tartu University Hospital; 2 University of Tartu, Department of Pediatrics; 3 Department of Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia. BACKGROUND X- linked mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) have been identified in female patients with epileptic encephalopathy and severe intellectual disability with a Rett-like phenotype (1). Epilepsy in CDKL5-related epileptic encephalopathy is characterized by early onset during the first 6 months of life. CDKL5-related epilepsies are usually therapy resistant (2). CLINICAL CASE R. was born on term from uneventful pregnancy, as her parents’ first child. At the age of 2 months she was referred to pediatric neurologist due to epileptic seizures described as series of spasms. Before that she’s been a healthy child. Neurologic examination showed poor psychomotor development: lack of eye contact and also severe hypotonia. Despite treatment with valproic acid, seizures continued. - At 4 months she had poor head control, lack of emotional contact and still persistent hypotonia. She presented spasms and tonic-clonic seizures 2-10 times per day. EEG showed some focal origin and secondary generalized epileptic discharges from right hemisphere with a normal baseline activity. MRI showed no structural abnormalities. - At 6 months myoclonic seizures developed. Several anti-epileptic drugs (AED) and their combinations were used without any effect. EEG at this point showed bilateral paroxysms of spikes and slow waives. Different genetic tests were performed: - basic metabolic analysis - POLG and GLUT1 gene sequencing, all showed normal results. - MRI and MRS (magnetic resonance spectroscopy) were done repeatedly without any abnormalities. Electroneuromyography, ECG, US of heart and other organs were normal. Treatment with ketogenic diet was tried, but with no effect. In CDKL5 gene sequence analyze a heterozygous mutation c.1648C>T (p.R550X) was found in exon 12 of CDKL5 gene and the diagnose of an autosomal dominant X-linked epileptic encephalopathy (atypical Rett syndrome) was made. - At 1.5 years the girl had a severe developmental delay: highest motor function was rolling over both sides, brief eye contact was present but no smiling or active communication. Severely decreased muscle tone persisted. She had no difficulties with swallowing or eating. Myoclonic seizures were present up to 10 times a day. No effect of any AED’s was achieved. EEG at 11 months: ictal and interictal myoclonias in sleepEEG at 1y6m: multifocal interictal discharges in sleep CONCLUSION This was the very first case of CDKL5 epileptic encephalopathy in Estonia. We suggest that genetic testing of CDKL5 gene should be considered in girls with early-onset epileptic encephalopathy and Rett syndrome-like features. Further communication: REFERENCES 1.Castrén, M. et al. Epilepsy caused by CDKL5 mutations. Eur J Ped Neurol. 1 5 ( ) 6 5e6 9 2.Jähn, J. et al. CDKL5 Mutations as a Cause of Severe Epilepsy in Infancy: Clinical and Electroencephalographic Long-term Course in 4 Patients. J Child Neurol (2012) 00(0) 1-5