S116 E U R O P E A N J O U R N A L O F P A E D I A T R I C N E U R O L O G Y 1 7 s ( 2 0 1 3 ) S 1 – S 1 4 9

Neurogenetic disorders

P228 - 2031Preliminary results of the study of Rett syndrome phenotype in27 patients from a Romanian pediatric neurology clinic

Anghelescu C, Barca D, Burloiu C, Butoianu N, Darja M,Gherghiceanu R, Iliescu C, Gos M, Hoffman-Zacharska D,Iancu D, Minciu I, Motoescu C, Sandu C, Tarta-Arsene O,Todorova A, Craiu D. Pediatric Neurology Department, Al. ObregiaHospital, Bucharest, Romania – dcraiu@yahoo.com

Background: Rett Syndrome (RTT) is an X-linked neurodevelop-mental disorder often caused by MECP2 mutations, characterizedby acquired microcephaly, loss of purposeful hand skills andspoken language, gait abnormalities and stereotypic hand move-ments. Epilepsy affects 50%-90% patients. Objectives: Preliminaryresults of RTT study in Pediatric Neurology Clinic of “Al. Obre-gia Hospital”, Bucharest, between 2010 and 2012 are presented.Material and methods: A Rett database was created in 2009. In2010 the file template was improved according to the Interna-tional Rett Registry. An evaluation protocol including clinicaland neurologic examination, imaging, EEG, biochemical, geneticevaluation was designed, for homogenous approach of the Rettphenotype patients. Genetic testing was performed in Genica lab-oratory (Bulgaria) and Warsaw (Poland) within the EuroepinomicsConsortium. Results: 27 female patients aged 8 month to 14 yearsat clinical RTT diagnosis were identified. 12 patients had a muta-tion in MECP2 gene; 11 are still being analysed. 15 patients (55%)had epilepsy. In 80% of patients, epilepsy started before age 5years. Only 4 of them were seizure-free. 2 patients with seizures’onset before age 12 months and early psychomotor regressiondeveloped highly drug-resistant epilepsy. 73% of patients werereceiving polytherapy. Two patients with p.R168X mutation werehighly AEDs resistant. In other 2 patients with p.R255X (associ-ated with epilepsy in the literature), only one had early onsetresistant epilepsy and severe clinical regression; the other keptprehension and gait, mild mental retardation and no epilepsy.Conclusions: No significant clinical-genetic correlations may berealised, due to small number of identical mutations in our smallgroup. Young age at epilepsy onset was a bad prognostic factorfor response to AEDs Phenotypic and genotypic variability arefrequent in RTT. More factors may be involved in RTT clinicalpicture and outcome. This database created premises for futureresearch in RTT in our clinic.

P229 - 2000Different clinical progress and genetic mutations of Laforadisease

Poyrazoglu HG, Per H, Karaca E, Canpolat M, Gumus H,Ozkınay F, Kumandas S. Erciyes Unv. Child Neurology Deparment,Kayseri, Turkey – hgpoyrazoglu@yahoo.com

Introduction: Lafora disease (LD) is a rare, autosomal recessiveform of progressive myoclonic epilepsy characterized by a severecourse. It is due to either the EPM2A or EPM2B gene mutations.The diagnosis of LD in our patient was based on the typicalclinical picture and confirmed by not only showing polyglucocaninclusions in skin biopsy but also evaluating the molecular ge-netic findings. We describe two different genetic mutations anda fatal clinical course of LD with homozygote NHLRC1 muta-tion and a novel homozygote EPM2A mutation. Cases 1 & 2: Twosiblings (16 year-old girl and 14 year old boy) followed up with ju-venile myoclonic epilepsy were admitted to our department withintractable seizures and cognitive dysfunction. On neurologicalexaminations; she was conscious and cooperated. Cognitive im-pairment, mild ataxia and dysarthria were determined. He wasrevealed no pathological findings except for mild mental retar-

dation. Their routine laboratory tests were normal. Her cranialmagnetic resonance imaging (MRI) revealed mild cerebral andcerebellar atrophy and his MRI was normal. Their EEG showedmultifocal localized, spike-polyspike wave discharges and burstof non-rhythmic slow activity. Lafora bodies were observed intheir axillary skin biopsy. A novel mutation of EPM2A gene (ho-mozygous p.Y112X(c.336C>A) was identified. Case 3: 14 year-oldgirl was admitted to our clinic with therapy-refractory seizureswith visual aura (sometimes) followed by generalized tonic-clonicseizures. Initial neurological examination was normal. After 6months, cognitive impairment, ataxia in the trunk and limbswere added. Routine laboratory tests were normal.Her cranialMRI was also normal. EEG showed spike-multispike wave dis-charge. Lafora bodies were observed in the axillary skin biopsy.A mutation of NHLRC1 gene (homozygous c.199 G>T(p.E67X)was identified. Clinical course developed rapidly progressive. Shebecame bedridden and died after 18 months of her admission.Discussion: Generally, mutations in the NHLRC1 gene were asso-ciated with a more benign clinical course compared with EPM2Amutations. Here, we describe a rapidly progressive form of LDwith NHLRC 1 mutation.

P230 - 1840Griscelli syndrome type 2, an exceptional onset

Olabarrieta N, Martinez MJ, Astigarraga I. Hospital Universitario deCruces (Barakaldo), Spain – naiara.olabarrietahoyos@osakidetza.net

Introduction: Griscelli syndrome type 2 is a rare autosomal re-cessive disorder of partial albinism and inmunodeficiency. Thisgenetic disorder of lymphocyte cytotoxicity predisposes patientsto haemophagocytic lymphohistiocytosis (HLH). Central nervoussystem involvement is frequent in HLH and neurologic symp-toms may complicate and even dominate the clinical picture.We report a new case showing predominant neurological in-volvement. Case report: A 5-years-old girl, the only child ofnonconsanguíneous parents, with history of recurrent acuteotitis media, perianal herpes and episode of gait disturbance,assumed as labyrinthitis. She was admitted because of vomit-ing, decreased level of conciousness and seizure, without fever.Neurological examination was normal. Cerebroespinal fluid testshowed pleocytosis. EEG was normal. The brain MRI revealed dif-fuse changes of supra and infratentorial whitte matter in frontal,temporal and parietal bilateral lobes, cerebellum, thalamus andbrainstem, with marked perilesional edema. Acute disseminatingencephalomyelitis was suspected, and high doses of methylpred-nisolone were administred with good response. Three monthslater, she was readmitted because of vomiting and headache.Her examination persisted normal. MRI showed progression witha new giant pseudotumoral lesion in left frontal whitte matterthat crossed through the corpus callosum. Oligoclonal IgG bandswere not present. Laboratory evaluations were normal. Due tothe neuroimaging findings with minimal involvement of the neu-rological examination, it is suspected a cerebral HLH, withoutsystemic involvement. On examination, she was noted to havesilvery grey hair. In her lactant period photographies she hadwhite hair, supports partial albinism. Electron microscopy of hairshaft and genetic studies established the diagnosis of Griscellidisease type 2 with RAB27A mutations. Conclusions:We report aGriscelli syndrome type 2 case with an exceptional onset: severeneuroimaging findings without clinical involvement, and HLHcompatible, without usual criteria of laboratory parameters. Tosum up we presume the clinical spectrum of this pathology isenlarged.