P08.10 Klinefelter syndrome and other sex-chromosomal bnormalities

S68 Poster sessions

Conclusion: The association between XYY syndrome, mul-tiple hereditary exostoses and epilepsy has not to ourknowledge been described. This case also shows the need formore studies on the eletroclinical traits of epilepsy in childrenwith XYY syndrome.

P08.10 Klinefelter syndrome and other sex-chromosomalabnormalities

I. Hsairi1 *, H. Ben Othmen2, N. Belghith3, E. Ellouz1,F. Kamoun1, H. Kamoun3, C. Triki1. 1Departement of childneurology research unit neuropediatrie, Tunisia, 2Research unitneuropediatrie; 3Laboratory of Molecular Genetics, Department ofgenetics, Tunisia

Background: A great number of sex-chromosomal abnormal-ities (SCA) have been detected associated with mental retar-dation (MR). They are expressed phenotypically in differentkinds of syndromes: Klinefelter, Turner’s syndrome...Methods: A prospective study was conducted on 270 childrenwith MR. They were subjected to a detailed family history,physical examination with photographs. Karyotype analysiswas done and genomic DNA was extracted in all cases.Results: SCA were finding in four children with mild MR.Two male were diagnosed as KF syndrome. The first one,11 years old, was followed for learning disabilities. Herclinical examination was normal.The second case, 2 years oldchild, had facial dysmorphology, hypotonia and ambiguousgenitalia. The karyotype confirmed respectively the diagnosisof classic KS and KS variant. Mutations in MeCP2 have beenscreened.In the third case, a 11 years old girl was followed for learningdisability, short stature, and macroglossia. The karyotypeshowed a mosaicism 47,XXX/45,X. The second girl was agedof 17 years, with the chief complaint of epilepsy since theage of 2 years. A new history of primary amenorrhea leadsto perform a karyotype revealing an XY female. She hadintact SRY and FMR1 gene. We suggest genetic analysis inthe androgen receptor gene.Conclusion: Screening for SCA by karyotype should beperformed on mild mentally retarded children especiallythose with dysmorphy or genital abnormalities. We stressedon a multidisciplinary approach in order to reach promptdiagnosis, best follow up and focus on X-linked gene in someSCA.

P08.11 Macrocephaly, dysmorphic features, West syndomeand Mental Motor Retardation due to unbalancedsegregation of familial reciprocal translocationbetween chromosomes 8 and 9

I. Erol1, S. Saygi1 *, F. Alehan1, F. Sahn2. 1Department ofpediatrics, Division of Child Neurology, Baskent University Facultyof Medicine, Turkey, 2Department of Medical Genetics, BaskentUniversity Faculty of Medicine, Turkey

NR3C2 or mineralocorticoid receptor mutations are theprincipal cause of autosomal dominant or sporadic type 1pseudohypoaldosteronism. Patients can be asymptomaticor show a salt-loosing syndrome in the neonatal period.Afterwards, patients compensate for their defective miner-alocorticoid receptors by upregulating their mineralocorticoidaxis, hence presenting, in most cases, a lifelong increase inrenin and aldosterone levels.The renin angiotensin aldosterone system (RAAS) is a keyhormonal system regulating blood pressure by acting onvasculature, heart, kidney and adrenal gland. However,expression of RAAS components has recently been detectedin other tissues such as brain, thymus and immunecells. Moreover, the RAAS has been implicated in severalmouse models of autoimmune disease. Series of studieshave demonstrated that angiotensin II has a wide varietyof proinflammatory properties which may contribute to

the development of autoimmune diseases. Notably, an-giotensin II seems to play a role in sustaining autoimmuneneuroinflammation in chronic experimental autoimmuneencephalomyelitis, a model mimicking many aspects ofmultiple sclerosis (MS), and angiotensin receptors are up-regulated in infiltrates of plaques from the brains ofMS patients.We report on a male patient who presented at the age of12 years with MS and in whom an inherited microdeletionwithin the NR3C2 gene was detected, compatible with thediagnosis of type 1 pseudohypoaldosteronism. His motherand her sister, who both developed autoimmune thyroiditis,also carry the microdeletion. The clinical relevance ofthis microdeletion in developing autoimmune diseases, andespecially in developing MS, is discussed.

P09. Neurooncology and neurocutaneous disorders

P09.1 Everolimus therapy for subependymal giant-cellastrocytomas (SEGAs) associated with tuberoussclerosis complex (TSC) following surgical resectionand tumor recurrence

D.N. Franz1 *, K.D. Agricola1, C.A. Tudor1, D.A. Krueger1.1Cincinnati Children’s Hospital, Medical Center, University ofCincinnati, College of Medicine, United States

Background: Tuberous sclerosis complex (TSC) is a geneticdisorder that produces multiple hamartomas. Neuronalmanifestations of TSC vary, but can include developmentof subependymal giant-cell astrocytomas (SEGAs). Currently,standard treatment for SEGAs is surgical resection. Recently,we conducted a phase I/II study of the mTOR inhibitoreverolimus as a treatment forTSC patients with SEGAs,whichshowed significant reductions in SEGA volume and seizurefrequency.Aim: In this subgroup analysis, we evaluated the safetyand efficacy of everolimus for treatment of SEGAs in TSCpatients with prior surgical resection and subsequent tumorrecurrence.Methods:TSC patients with demonstrated serial SEGA growthwere eligible to receive everolimus (3mg/m2/d, titrated towhole-blood trough concentrations of 5−15 ng/mL) as partof a single-arm, single-center phase I/II study. We assessedsafety and efficacy outcomes among the subset of studypatients with prior surgical resection of SEGAs.Results: Of the 28 study patients, 4 (14.3%) had experi-enced surgical tumor resection prior to enrollment. Twoof these patients had 2 prior surgeries. In one case,surgery was complicated by white matter volume lossand intraventricular hemorrhage requiring shunt placement.Following everolimus therapy, all 4 patients experienceda >50% reduction in SEGA volume (range, 51%-79%). In 1patient, SEGA volume decreased by 65% before returning tobaseline, but since has remained stable and not requiredsurgery.Conclusions: Everolimus is a viable treatment option forSEGAs in TSC patients who have undergone previous surgicalresection, which can avoid the progressive complicationsassociated with surgical resection.

P09.2 Structural integrity of normal appearing white matterrelates to intelligence in tuberous sclerosis complex

S.M. Koudijs1 *, J.S. van Campen1, O.B. Braams1, A. Leemans1,O. van Nieuwenhuizen1, K.P.J. Braun1, F.E. Jansen1. 1UniversityMedical Center, Utrecht, Netherlands

Purpose: To study the relation between intelligence anddiffusion tensor imaging (DTI) characteristics of normal