1Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Departamento de Radiologia, Campinas SP, Brazil. 2Pontifícia Universidade Católica de São Paulo, Faculdade de Ciências Médicas e da Saúde, Departamento de Neuropediatria, Sorocaba SP, Brazil. 3Universidade Federal do Rio Grande do Sul, Faculdade de Ciências Médicas, Departamento de Radiologia, Porto Alegre RS, Brazil. 4The University of Mississippi Medical Center, School of Medicine, Department of Radiology, Jackson, MS, USA. 5Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Departamento de Neurologia, Campinas SP, Brazil. LFMB  https://orcid.org/0000-0003-2661-4791; FVP  https://orcid.org/0000-0002-0828-7806; PMPM  https://orcid.org/0000-0001-9041-5047; JAD  https://orcid.org/0000-0003-4973-2889; LLV  https://orcid.org/0000-0002-9532-1178; TR  https://orcid.org/0000-0001-8453-0313; MCFJ  https://orcid.org/0000-0003-0898-2419; FR  https://orcid.org/0000-0003-2256-4379 Correspondence: Luiz Fernando Monte Borella; Email: borella.luiz@gmail.com. Conflict of interest: There is no conflict of interest to declare. Authors’ contributions: LFMB: conceptualization (supporting), data curation (supporting), investigation (supporting), writing-original draft (lead); FVP, PMPM, JAD, LLV, TR, MCFJ: conceptualization (equal), visualization (equal), writing-review & editing (equal); FR: conceptualization (lead), formal analysis (lead),project administration (lead), visualization (lead), writing-review & editing (lead). Received on July 27, 2021; Received in its final form August 11, 2021; Accepted on 19 August 2021. Widening the spectrum of lama 2 congenital muscular dystrophy (mDC1a): cobblestone malformation

A 7-year-old boy with hypochondroplasia had neurodevelopmental delay, mild cognitive impairment, subtle motor deficits and without epilepsy. There was no obstetric problem or perinatal impairment. Genetic revealed the p.N540K FGFR3 variant. MRI findings are depicted (). […] New Magnetic Resonance Imaging (MRI) findings in a patient with hypochondroplasia caused by the FGFR3 N540K variant

We studied 14 patients with severe myoclonic epilepsy of infancy (SMEI), mean age +/- SD 8.5 +/- 4.14 yr, 10 girls, and 13 patients with myoclonic astatic epilepsy (MAE), mean age +/- SD 11.8 +/- 5.19 yr, six girls. All patients underwent EEGs, cranial magnetic resonance imaging (MRI) and the Vineland scale for assessment of adaptive behavior in areas related to communication, activities of daily living, socialization, and motor skills. Our study revealed abnormalities in the neurological examination (ataxia, mild pyramidal tract abnormalities, hyperactivity, autism spectrum disorder) in all 14 patients with SMEI and 4 of the 8 patients with MAE. EEGs showed background slowing, and focal and generalized epileptiform activity in 10 patients with SMEI. In patients with MAE EEGs showed monomorphic centroparietal theta rhythm in nine patients, and generalized epileptiform activity in all patients. Deterioration of adaptive behavior occurred in all the patients with SMEI and in eight patients with MAE. SMEI and MAE showed clinical and EEG findings according to those previously described. Nevertheless, severe epileptic encephalopathy was detected in patients with SMEI while patients with MAE presented with a milder form of epileptic encephalopathy. The outcome was good in approximately one third of the patients with MAE.

OBJECTIVES: The purpose of this study was to advance the knowledge on the clinical use of SCN1A testing for severe epilepsies within the spectrum of generalized epilepsy with febrile seizures plus by performing genetic screening in patients with Dravet and Doose syndromes and establishing genotype-phenotype correlations. METHODS: Mutation screening in SCN1A was performed in 15 patients with Dravet syndrome and 13 with Doose syndrome. Eight prediction algorithms were used to analyze the impact of the mutations in putative protein function. Furthermore, all SCN1A mutations previously published were compiled and analyzed. In addition, Multiplex Ligation-Dependent Probe Amplification (MLPA) technique was used to detect possible copy number variations within SCN1A. RESULTS: Twelve mutations were identified in patients with Dravet syndrome, while patients with Doose syndrome showed no mutations. Our results show that the most common type of mutation found is missense, and that they are mostly located in the pore region and the N- and C-terminal of the protein. No copy number variants in SCN1A were identified in our cohort. CONCLUSIONS: SCN1A testing is clinically useful for patients with Dravet syndrome, but not for those with Doose syndrome, since both syndromes do not seem to share the same genetic basis. Our results indicate that indeed missense mutations can cause severe phenotypes depending on its location and the type of amino-acid substitution. Moreover, our strategy for predicting deleterious effect of mutations using multiple computation algorithms was efficient for most of the mutations identified.

OBJECTIVES: The purpose of this study was to advance the knowledge on the clinical use of SCN1A testing for severe epilepsies within the spectrum of generalized epilepsy with febrile seizures plus by performing genetic screening in patients with Dravet and Doose syndromes and establishing genotype-phenotype correlations. METHODS: Mutation screening in SCN1A was performed in 15 patients with Dravet syndrome and 13 with Doose syndrome. Eight prediction algorithms were used to analyze the impact of the mutations in putative protein function. Furthermore, all SCN1A mutations previously published were compiled and analyzed. In addition, Multiplex Ligation-Dependent Probe Amplification (MLPA) technique was used to detect possible copy number variations within SCN1A. RESULTS: Twelve mutations were identified in patients with Dravet syndrome, while patients with Doose syndrome showed no mutations. Our results show that the most common type of mutation found is missense, and that they are mostly located in the pore region and the N- and C-terminal of the protein. No copy number variants in SCN1A were identified in our cohort. CONCLUSIONS: SCN1A testing is clinically useful for patients with Dravet syndrome, but not for those with Doose syndrome, since both syndromes do not seem to share the same genetic basis. Our results indicate that indeed missense mutations can cause severe phenotypes depending on its location and the type of amino-acid substitution. Moreover, our strategy for predicting deleterious effect of mutations using multiple computation algorithms was efficient for most of the mutations identified.