Summary:Purpose: To evaluate how diagnostic criteria influence remission rates for patients with childhood absence epilepsy (CAE) and to assess clinical and EEG parameters as predictors of outcome.Methods: One hundred nineteen patients were diagnosed with CAE, according to International League Against Epilepsy (ILAE) classification criteria. They were subsequently evaluated according to stricter diagnostic criteria. Sixty-two subjects fulfilled these criteria as group 2; 57 did not and constituted group 1. Diagnostic parameters that prevented patients of group 1 from entering group 2, and variables such as sex, familial history of generalized epilepsy, and personal history of febrile convulsions also were tested as prognostic factors for terminal remission.Results: Compared with those in group 1, patients of group 2 had significantly higher rates of seizure control (95% vs. 77%), higher rates of terminal remission (82% vs. 51%), fewer generalized tonic-clonic seizures (8% vs. 30%), and shorter mean periods of treatment (2.2 vs. 3.8 years). Significantly fewer patients were receiving polytherapy in group 2 than in group 1 (11% vs. 47%), and fewer patients had seizure relapses at antiepileptic drug discontinuation (0 vs. 22%).Conclusions: Remission rates of patients with CAE are greatly influenced by the classification criteria used for selection. Stricter diagnostic criteria allow the definition of a homogeneous group of patients with excellent prognosis. Factors predicting unfavorable prognosis were generalized tonic-clonic seizures in the active stage of absences, myoclonic jerks, eyelid myoclonia or perioral myoclonia, and EEG features atypical for CAE.

Neurofibromatosis 1 is the most common neurocutaneous disease. Neurologic manifestations are mainly represented by tumors such as optic gliomas, focal areas of high T2-weighted signal known as unidentified bright objects, and mental retardation or learning disabilities. The prevalence of seizures has been reported to range from 3.8 to 6%. In the present study, we evaluated prevalence, type, and etiology of epilepsy in a neurofibromatosis 1 population. A retrospective analysis of 198 patients affected by neurofibromatosis 1 was performed. Fourteen patients (7%) were found to be epileptic. Every patient underwent electroencephalographic examination and neuroimaging investigations. Thirteen were submitted to magnetic resonance imaging (MRI) study and one to computed tomographic (CT) scanning. Single-photon emission computed tomographic and positron emission tomographic studies were performed in a few selected cases. Seizures were partial in 12 of these (85%) and generalized in 2 (15%). In nine (64%), epilepsy was secondary to brain lesions: five of these had cerebral tumors (three with epilepsy as the fist symptom), three had cortical malformation, and one had mesial temporal sclerosis. Seizures were controlled rapidly in eight (57%) and drug resistant in four (29%). Two patients were lost at follow-up. All patients with uncontrolled seizures had severe mental retardation, and three of these had malformations of cortical development. Our observations and our re-evaluation of the literature indicate that patients with neurofibromatosis 1 have an increased risk of epilepsy related to intracranial masses and cytoarchitectural abnormalities, and seizures can represent the first symptom of a tumor or cortical malformation. Brain MRI and, in selected cases, functional studies appear to be useful in patients with neurofibromatosis 1 who present with seizures, especially if associated with mental retardation.

The present report describes a 7-year-old girl with a de novo 3 Mb interstitial deletion of chromosome 14q12, identified by oligo array-CGH. The region is gene poor and contains only five genes two of them, FOXG1B and PRKD1 being deleted also in a previously reported case with a very similar phenotype. Both patients present prominent metopic suture, epicanthic folds, bulbous nasal tip, tented upper lip, everted lower lip and large ears and a clinical course like Rett syndrome, including normal perinatal period, postnatal microcephaly, seizures, and severe mental retardation. FOXG1B (forkhead box G1B) is a very intriguing candidate gene since it is known to promote neuronal progenitor proliferation and to suppress premature neurogenesis and its disruption is reported in a patient with postnatal microcephaly, corpus callosum agenesis, seizures, and severe mental retardation.

Tyrosinemia type II (Richner-Hanhart syndrome, RHS) is a disorder of autosomal recessive inheritance characterized by keratitis, palmoplantar hyperkeratosis, mental retardation, and elevated blood tyrosine levels. The disease results from deficiency in hepatic tyrosine aminotransferase (TAT). We have previously described one deletion and six different point mutations in four RHS patients. We have now analyzed the TAT genes in a further seven unrelated RHS families from Italy, France, the United Kingdom, and the United States. We have established PCR conditions for the amplification of all twelve TAT exons and have screened the products for mutations by direct sequence analysis or by first performing single-strand conformation polymorphism analysis. We have thus identified the presumably pathological mutations in eight RHS alleles, including two nonsense mutations (R57X, E411X) and four amino acid substitutions (R119W, L201R, R433Q, R433W). Only the R57X mutation, which was found in one Scottish and two Italian families, has been previously reported in another Italian family. Haplotype analysis indicates that this mutation, which involves a CpG dinucleotide hot spot, has a common origin in the three Italian families but arose independently in the Scottish family. Two polymorphisms have also been detected, viz., a protein polymorphism, P15S, and a silent substitution S103S (TCG-->TCA). Expression of R433Q and R433W demonstrate reduced activity of the mutant proteins. In all, twelve different TAT gene mutations have now been identified in tyrosinemia type II.

Hypochondroplasia (HCH) and Muenke syndrome (MS) are caused by mutations on FGFR3 gene. FGFR3 is known to play a role in controlling nervous system development. We describe the clinical and neuroradiological findings of the first two patients, to our knowledge, affected by HCH and MS, respectively, in whom bilateral dysgenesis of the medial temporal lobe structures has been observed. In both patients diagnosis was confirmed by molecular analysis. They were mentally normal and showed similarities in early-onset temporal lobe-related seizures. In both patients EEG recorded bilateral temporal region discharges. MRI detected temporal lobe anomalies with inadequate differentiation between white and gray matter, defective gyri, and abnormally shaped hippocampus.