Trehalose Ameliorates Zebrafish Emotional and Social Deficits Caused by CLN8 Dysfunction.

CLN8 and other neuronal ceroid lipofuscinoses (NCLs) often lead to cognitive decline, emotional disturbances, and social deficits, worsening with disease progression. Disrupted lysosomal pH, impaired autophagy, and defective dendritic arborization contribute to these symptoms. Using a zebrafish model, we identified significant impairments in locomotion, anxiety, and aggression, along with subtle deficits in social interactions, positioning zebrafish as a useful model for therapeutic studies in NCL.

Glucose metabolism impairment as a hallmark of progressive myoclonus epilepsies: a focus on neuronal ceroid lipofuscinoses.

Glucose is the brain's main fuel source, used in both energy and molecular production. Impaired glucose metabolism is associated with adult and pediatric neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), GLUT1 deficiency syndrome, and progressive myoclonus epilepsies (PMEs). PMEs, a group of neurological disorders typical of childhood and adolescence, account for 1% of all epileptic diseases in this population worldwide.

Coffin-Siris and Nicolaides-Baraitser syndromes are a common well recognizable cause of intellectual disability.

Background: Nicolaides-Baraitser and Coffin-Siris syndromes are emerging conditions with overlapping clinical features including intellectual disability and typical somatic characteristics, especially sparse hair, low frontal hairline, large mouth with thick and everted lips, and hands and feet anomalies. Since 2012, mutations in genes encoding six proteins of the BAF complex were identified in both conditions.

Methods And Results: We have clinically evaluated a cohort of 1161 patients with intellectual disability from three different Italian centers.

A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling.

Chromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. De novo dominant mutations in different members of the SWI/SNF chromatin remodeling complex have recently been described in individuals with Coffin-Siris (CSS) and Nicolaides-Baraitser (NCBRS) syndromes. Using a combination of whole-exome sequencing, NGS-based sequencing of 23 SWI/SNF complex genes, and molecular karyotyping in 46 previously undescribed individuals with CSS and NCBRS, we identified a de novo 1-bp deletion (c.

Evaluation of tibial osteopathy occurrence in neurofibromatosis type 1 Italian patients.

Neurofibromatosis Type 1 (NF1) is a common autosomal dominant disorder characterized by high penetrance, widely variable expressivity and occurrence of specific skeletal changes such as tibial osteopathy (TO). We collected data on patients referred to the Italian Neurofibromatosis Study Group in order to compare clinical features between 49 NF1 patients with TO, and 98 age-matched NF1 patients without TO, and to determine whether the presence of TO is associated with a different risk of developing the typical NF1 complications. We assessed both groups for: age at diagnosis of NF1, gender distribution, family history, gender inheritance, presence of scoliosis, sphenoid wing osteopathy, other skeletal abnormalities, macrocrania, hydrocephalus, plexiform neurofibromas, tumors, optic pathway gliomas, T2H (high-signal intensity areas on T2 weighted brain MRI), epilepsy, headache, mental retardation, cardiovascular malformations, and Noonan phenotype.

Quantitative ultrasound and dual-energy x-ray absorptiometry in children and adolescents with neurofibromatosis of type 1.

Reduced areal bone mineral density (aBMD) is a common feature of neurofibromatosis type 1 (NF1). Moreover, in recent years there has been a growing interest in using quantitative ultrasound (QUS) for the evaluation of bone status. In 55 NF1 subjects (mean age: 9.

Schwannomatosis associated with multiple meningiomas due to a familial SMARCB1 mutation.

Schwannomatosis (MIM 162091) is a condition predisposing to the development of central and peripheral schwannomas; most cases are sporadic without a clear family history but a few families with a clear autosomal dominant pattern of transmission have been described. Germline mutations in SMARCB1 are associated with schwannomatosis. We report a family with multiple schwannomas and meningiomas.

Late-onset childhood occipital epilepsy (Gastaut type): a family study.

Late onset childhood occipital epilepsy-Gastaut type (LOCOE) is a rare idiopathic epilepsy syndrome with an uncertain long-term prognosis. Elementary visual hallucinations and interictal spike-and-wave complexes in the occipital areas represent the main electroclinical findings of the syndrome. The functional nature of LOCOE has been emphasized together with the presence of genetic predisposition in the affected patients.

Incident reporting in anesthesia: misidentification of propofol concentrations due to similarities in drug packaging.

We report three cases of misidentification of propofol concentrations due to similarities in drug packaging, which were identified by the incident reporting system. Incident reporting is an approach used to assess the incidence of adverse and potentially adverse events, established to manage the contributing factors and to develop appropriate strategies to prevent errors in anesthesia. Inadvertently, 2% propofol was administered instead of 1%, causing overdosage and prolonged anesthesia in two consecutive patients in the same operating room.

Efficacy and safety of topiramate in infants according to epilepsy syndromes.

Studies of the efficacy of topiramate (TPM) in infants and young children are few. Here we report an open, prospective, and pragmatic study of effectiveness of TPM in terms of epilepsy syndromes, in children aged less than 2 years. The median follow-up period was 11 months.

Craniofacial dyssynostosis: case report and review.

Craniofacial dyssynostosis (CFD) is a rare disorder related to premature closure of the lambdoid suture and the posterior part of the sagittal suture. Epilepsy, mental retardation, abnormalities of the corpus callosum, and short stature have been reported. We studied a patient with CFD, hydronephrosis, and partially empty sella turcica; the latter two features are reported for the first time.

Malformations of cortical development in neurofibromatosis type 1.

The authors report three patients with neurofibromatosis type 1 and different types of malformations of cortical development: Patient 1 had a possible transmantle cortical dysplasia involving the right temporoinsuloparieto-occipital areas; Patient 2 had a periventricular band of heterotopic gray matter with an overlying pachygyric cerebral cortex; and Patient 3 had a left perisylvian polymicrogyria. Because all of these lesions result from different pathogenetic mechanisms, neurofibromin may play a role during several stages of cortical development.

Epilepsy in neurofibromatosis 1.

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.

Nucleotide variation in Sabin type 2 poliovirus from an immunodeficient patient with poliomyelitis.

The molecular and antigenic properties of a Sabin-like type 2 poliovirus, isolated from the stool samples of a 2-year-old agammaglobulinaemic child who developed paralysis 1 year after receiving the third dose of oral poliovirus vaccine, were analysed. The virus revealed 0.88 % genome variation in the VP1 region compared with the standard reference strain, compatible with replication of the virus in the intestine over approximately 1 year.

GM2 gangliosidosis variant B1 neuroradiological findings.

Variant B1 is a rare type of GM2 gangliosidosis. Clinically, it shows a wide spectrum of forms ranging from infantile to juvenile. We report the first magnetic resonance imaging (MRI) findings from three patients affected by GM2 gangliosidosis variant B1, two presenting with the infantile form and one with the juvenile form.

Familial Axenfeld-Rieger anomaly, cardiac malformations, and sensorineural hearing loss: a provisionally unique genetic syndrome?

Axenfeld-Rieger anomaly (ARA) is an autosomal dominant disorder of the anterior chamber of the eye that includes a prominent and anteriorly displaced Schwalbe line and an iridocorneal synechiae, and is associated with iris hypoplasia, corectopia, and hole formation. Extraocular developmental abnormalities, especially of the teeth, facial bones, and periumbilical skin, have also been reported with ARA, in the context of the so-called Axenfeld-Rieger syndrome (ARS). Genetic heterogeneity exists, as ARA maps to chromosome 6p25, whereas ARS can be linked to both chromosome 4q25 and chromosome 13q14.

Pseudo-TORCH syndrome or Baraitser-Reardon syndrome: diagnostic criteria.

Intracranial calcification and microcephaly, which represent the main clinical features of the TORCH-syndrome, can also be determined by a rare autosomal recessive infection-like condition named pseudo-TORCH syndrome. This emerging entity has been registered in eight families so far. We report on five patients from three unrelated Italian families affected by pseudo-TORCH syndrome.

Neurofibromatosis type 2 attributable to gonosomal mosaicism in a clinically normal mother, and identification of seven novel mutations in the NF2 gene.

Neurofibromatosis type 2 (NF2) is an autosomal dominant cancer syndrome that predisposes to the development of bilateral vestibular schwannomas sometimes associated with schwannomas at other locations, meningiomas, ependymomas and juvenile posterior subcapsular lenticular opacities. This disease is caused by inactivating mutations in the NF2 tumour-suppressor gene, located in 22q12. Recently, somatic mosaicism has been demonstrated in some "de novo" NF2 patients.

[Premedication with intranasal midazolam in children of various ages].

Background And Aim: To evaluate the efficacy of premedication with midazolam (mdz) administered using a nasal route compared to diazepam (dz) administered by mouth in children of different ages.

Experimental Design: A comparative type study was performed in randomly selected pediatric patients undergoing surgery. The study lasted 3 months.

Central nervous system imaging in reevaluation of patients with neurofibromatosis type 1.

We report the results of the reevaluation of 24 patients with neurofibromatosis type 1 (NF1) using central nervous system (CNS) imaging techniques. The first examination by computed tomography (CT) or magnetic resonance imaging (MRI) indicated the presence of optic glioma in three cases, "unidentified bright objects" (UBOs) in six, and a suspected right frontal tumor in one. In two patients optic glioma and UBOs were both present and in one of them a bulbar tumor was also suspected.

Relationship between café-au-lait spots as the only symptom and peripheral neurofibromatosis (NF1): a follow-up study.

We re-examined 21 children with the possible diagnosis of peripheral neurofibromatosis (NF1) based on the presence of café-au-lait (CAL) spots as the single clinical finding. We evaluated whether "typical" or "atypical" appearance of the spots was important for the final diagnosis and whether the co-existence of other non-specific signs (e.g.

Diagnosis of neurofibromatosis type 1 using RFLPs tightly linked to gene.

This study reports the results of a linkage analysis in nine families with members who had neurofibromatosis type 1 (NF1), using five restriction fragment length polymorphisms (RFLPs) tightly linked to the NF1 locus. The purpose of this analysis was to determine whether the at-risk individuals were carrying the NF1 allele and whether the nine families would be informative for prenatal testing. The families included 25 patients with NF1, 3 individuals at risk for NF1, and 11 unaffected subjects, with a total of 39 family members and 12 matings.

11q- and constitutional X trisomy in a patient with M5b acute non-lymphocytic leukemia.

A patient with M5b acute nonlymphoblastic leukemia (ANLL) and a 47,XXX del(11) (q23) karyotype is described. Partial remission was obtained after treatment with daunorubicin, arabinosylcytosine and VP-16. Subsequently, two courses of chemotherapy for resistant ANLL were administered without achieving complete remission.

[Correlations between karyotype and phenotype in structural and numerical abnormalities of chromosome 18].

Five cases with different abnormalities of chromosome 18 are described: one case with trisomy 18, two cases with ring 18, one case with partial trisomy 18q and one case with a mosaic 18p-/iso 18q. The karyotypes of the parents were normal. Cytogenetic analysis was performed on PHA stimulated blood lymphocytes.

[Familial segregation of simple and complex chromosomal rearrangements].

We report our observations about familial segregations of chromosomal aberrations: the simple forms and complex rearrangements. Congenital malformations and mental retardation, can be present both in unbalanced and in balanced translocations. Various hypotheses have been proposed to explain this phenomenon: in particular a possible "position effect" or genic mutation or genomic imprinting.