Novel CTNNB1 variant leading to neurodevelopmental disorder with spastic diplegia and visual defects plus peripheral neuropathy: A case report.

Pathogenic variants in the ß1-catenin (CTNNB1) gene have been identified in patients with various diseases, including syndromic intellectual disability, autism spectrum disorder, familial exudative vitreoretinopathy, and neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV). We report on the clinical, genetic, neuroimaging, and neurophysiological data of a 15-year-old patient with complex hereditary spastic paraplegias with exotropia, dyskinesia, and cerebellar signs and a so-far unreported demyelinating (mainly sensory) polyneuropathy in her lower limbs. She carries the novel, de novo, likely pathogenic heterozygous c.603_605delinsAATA, p.(Met202Ilefs*6) frameshift variant in the CTNNB1 gene. Although peripheral neuropathy was not previously associated with NEDSDV, in light of the role of ß1-catenin as a junction protein in the peripheral as well as in the central nervous system documented in experimental studies, it might represent a causally linked and under-reported finding to be further explored.

Paediatric-onset hereditary spastic paraplegias: a retrospective cohort study.

AIM: To describe the clinical and neurogenetic spectrum of paediatric-onset hereditary spastic paraplegias (HSPs) diagnosed in our unit. METHOD: We report on 47 patients (30 males, 17 females; mean [SD] age 12y 7mo [6y 2mo], range 4-34y) clinically diagnosed with an HSP at the Child Neurology Unit, IRCCS-ASMN (Reggio Emilia, Italy) between 1990 and 2018, who were genetically investigated by means of single-gene direct sequencing and/or next-generation sequencing technologies (targeted panels, whole-exome sequencing [WES]). RESULTS: Complex forms prevailed slightly (n=26), autosomal dominant being the main inheritance pattern (n=11), followed by recessive (n=5) and X-linked (n=1). A definite genetic diagnosis was achieved in 17 patients. Spastic paraplegia 3A (n=4) was the most frequent cause of autosomal dominant HSP in our cohort, while no genetic variant prevailed in autosomal recessive forms and pathogenic/likely pathogenic variants were disclosed in a wide range of different genes. INTERPRETATION: We found wide phenotypic and genetic heterogeneity. With increasing accessibility to WES, a higher number of patients receive a diagnosis, allowing detection of variants in ultra-rare disease-causing genes and refining genotype-phenotype correlations. WHAT THIS PAPER ADDS: A genetic diagnosis of paediatric-onset hereditary spastic paraplegia was achieved in one-third of patients. Pathogenic/likely pathogenic variants in rare genes were found. Genotypic and phenotypic heterogeneity favours targeted panel/whole-exome sequencing for diagnosis.

Neuropsychological implications of adjunctive levetiracetam in childhood epilepsy.

INTRODUCTION: Levetiracetam (LEV) is an effective antiepileptic drug also used in childhood and adolescence. Literature data regarding the long-term effects of LEV in childhood epilepsy and based on extensive neuropsychological evaluations using standardized tools are still scanty. Our study aimed to address this topic. MATERIALS AND METHODS: We studied 10 patients with epilepsy characterized by focal or generalized seizures (4 boys, 6 girls; mean age: 10 years 8 months; range: 6 years 2 months - 16 years 2 months), treated with adjunctive LEV during a follow-up of 12 months. In 6 patients electroencephalogram (EEG) showed continuous spike and waves during sleep. Using standardized tools, we performed seriated assessments of cognitive and behavioral functioning in relation to seizure and EEG outcome. RESULTS: Six patients completed the trial after 12 months of treatment; 1 patient dropped out of the study after 9 months, 3 patients after 6 months. Adjunctive LEV was effective on seizures in 3/10 patients and on EEG in 2/10 patients, and was well tolerated in all examined cases. Overall, no worsening of cognitive or behavioral functions has been detected during the period of the study; even at 6 and 12 months from baseline, an improvement in patients' abstract reasoning has been found, that was not related to seizure or EEG outcome. CONCLUSIONS: In our population of children and adolescents, LEV had no adverse cognitive or behavioral effects, short- or long-term. We found an improvement of abstract reasoning, regardless of seizure and EEG outcome.