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Background: The BUB 1 mitotic checkpoint serine/threonine kinase B (BUB1B) gene encodes a key protein in the mitotic spindle checkpoint, which acts as a surveillance mechanism, crucial for the maintenance of the correct chromosome number during cell deviation. Mutations of BUB1B gene are linked to mosaic variegated aneuploidy 1 (MVA1) syndrome, a rare autosomal recessive disorder characterized by widespread mosaic aneuploidies, involving different chromosomes and tissues. MVA1 is clinically characterized by intrauterine growth restriction, post-natal growth retardation, and severe neurologic impairment including microcephaly, developmental delay/intellectual disability, epileptic seizures, and generalized hypotonia. Malignancies are also serious sequelae associated with the disorder. We reported on a case of two-year-old Italian girl with MVA1 who shows severe neurologic impairment, microcephaly and epileptic seizures. Materials and methods: Clinical data collection and genetic diagnosis of the patient were assessed. Mutational analysis covers the chromosomal microarray analysis, the gene methylation pattern studied using the methylation-specific multiplex ligation-dependent probe amplification, and the family-based Whole Exome Sequencing (WES). A literature research based on reported cases of MVA and premature chromatid separation was also included. Results: Karyotyping has revealed 12% of mosaics in the patient who carries a novel variant in BUB1B gene (c.2679A > T, p.Arg893Ser) detected by WES. Thirty-one cases of MVA1 including the present report, and four prenatally diagnosed cases with MVA1 were selected and inspected. Conclusion: Clinical and genetic findings reported in the girl strongly suggest a new MVA1 genotype–phenotype correlation and lead to a reappraisal of a severe syndrome. Diagnosis and in-depth follow-up provided worthwhile data. [ABSTRACT FROM AUTHOR]

Acute autoimmune encephalitis is a severe neurological disorder presenting with altered level of consciousness, confusion, irritability, headache, vomiting, and in some cases seizures. An infective event precedes by 1–2 weeks the onset of the symptoms. Cognitive impairment is considered the cardinal symptom. The autoimmune encephalitis comprises an increasingly group of inflammatory brain disorder caused by an underlying abnormal immune response to the CNS to the infective agent. In children, several antibodies have been recorded as causative agent. Among these, GAD65, MOG, and NMDAR antibodies are more commonly reported and with less frequency, the Dopamine-2 receptor, GABA A receptor, GABA B receptor, and Glycinereceptorandm-GluR5. We report here a 10-year-old male with acute autoimmune encephalitis with altered status of consciousness and severe cerebral involvement at the brain-MRI. Serum and cerebrospinal fluid disclosed the presence of anti-AMPA-GluR3 antibodies suggesting a possible pathogenetic correlation with the disorder presented by the proband. Precocious treatment with intravenous methylprednisolone and immunoglobulin resulted in progressive but constant improvement. At 3-month follow-up, the clinical condition of the child and the neuro-radiological brain anomalies returned to the normal. At the 2-year follow-up, no recurrence or other disturbances were reported. [ABSTRACT FROM AUTHOR]

Since its first clinical description (on his son) by William James West (1793–1848) in 1841, and the definition of the classical triad of (1) infantile spasms; (2) hypsarrhythmia, and (3) developmental arrest or regression as "West syndrome", new and relevant advances have been recorded in this uncommon disorder. New approaches include terminology of clinical spasms (e.g., infantile (IS) vs. epileptic spasms (ES)), variety of clinical and electroencephalographic (EEG) features (e.g., typical ictal phenomena without EEG abnormalities), burden of developmental delay, spectrum of associated genetic abnormalities, pathogenesis, treatment options, and related outcome and prognosis. Aside the classical manifestations, IS or ES may present with atypical electroclinical phenotypes (e.g., subtle spasms; modified hypsarrhythmia) and may have their onset outside infancy. An increasing number of genes, proteins, and signaling pathways play crucial roles in the pathogenesis. This condition is currently regarded as a spectrum of disorders: the so-called infantile spasm syndrome (ISs), in association with other causal factors, including structural, infectious, metabolic, syndromic, and immunologic events, all acting on a genetic predisposing background. Hormonal therapy and ketogenic diet are widely used also in combination with (classical and recent) pharmacological drugs. Biologically targeted and gene therapies are increasingly studied. The present narrative review searched in seven electronic databases (primary MeSH terms/keywords included West syndrome, infantile spasms and infantile spasms syndrome and were coupled to 25 secondary clinical, EEG, therapeutic, outcomes, and associated conditions terms) including MEDLINE, Embase, Cochrane Central, Web of Sciences, Pubmed, Scopus, and OMIM to highlight the past knowledge and more recent advances. [ABSTRACT FROM AUTHOR]

Microcephaly is defined as a head circumference measurement of 2 or 3 standard deviations below the mean for age and sex. However, distinguishing the value of -2 or -3 standard deviations as a cutoff is relevant in the clinical practice, since the limit of -3 standard deviations is more frequently associated with cognitive impairment. The use of ultrasound scans in pregnancy has allowed the identification of subjects with a measurement of the head circumference at the limit of the cutoff for gestational age, but who do not subsequently show cognitive delay. The same is true for newborns with a -2 to -3 standard deviations cutoff, and without anomalous clinical signs, for which a cognitive delay is not easily diagnosed. In this case, to define an infant as being affected by microcephaly (with a prognosis usually recognized as harmful) may be unnecessarily distressful for parents or caregivers. In the cases mentioned, resuming the word "small head" instead of microcephaly to define such subjects could be more appropriate and more appreciated. [ABSTRACT FROM AUTHOR]

There is an ample evidence that hypopigmentation of the skin along the Blaschko's lines is frequently associated with neurological disorders. Nowadays, the term 'Hypomelanosis of Ito' (HI) is applied when, together with the cutaneous lesions, various and multisystem organs are involved. Among these, the most frequent are cerebral manifestations, such as cognitive delay and epileptic seizures. For this reason, hypomelanosis of Ito has been included in the group of neurocutaneous syndromes, neurologic manifestations being one of the most frequent. Epileptic seizures have been reported in patients with this disorder, but in a very few particular attention has been focused on the type and frequency of epilepsy and on the response to the treatment. Herein, we report on five patients with HI who showed episodes of epileptic seizures with onset in childhood, in absence of malformative anomalies except for the skin lesions. A survey on the frequency and types of epileptic seizures in HI children and in the literature is reported. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning a case study of big toe dorsal flection being questioned as pseudo-Babinski phenomenon or neuropodiatric curiosity.

The co-occurrence of microcephaly and Legg-Calvè-Perthes disease (LCPD) in members of the same family has been previously recorded only in two Hungarian brothers. To study the clinical and radiological phenotype in a (second) family with LCPD and microcephaly, clinical, X-ray and MRI follow-up study of two Albanian siblings aged 8 and 11 years, were made. Both siblings had primary microcephaly, seizures and mild-to-moderate mental retardation. At head imaging the boy was found to have skull asymmetry, partial lack of frontal lobe development and partial agenesis of corpus callosum and the girl had a complex brain malformation consisting in thickening of the fronto-temporal cortex, colpocephaly, increased curvature of the Sylvian fissure, elevated tentorium with mild hypoplasia of the cerebellar vermis and dilated cisterna magna. In addition, the brother had ADHD and the sister minor eye anomalies mainly consisting in epicanthic folds and pale bilateral (temporal) optic disk. We recorded (and documented for the first time by brain MRI) a second family with familial co-occurrence of LCPD and microcephaly and the first occurrence of complex brain anomalies in the context of a small head circumference. The present report could encourage the observation of similar cases. [ABSTRACT FROM AUTHOR]

The co-occurrence of microcephaly and Legg-Calvè-Perthes disease (LCPD) in members of the same family has been previously recorded only in two Hungarian brothers. To study the clinical and radiological phenotype in a (second) family with LCPD and microcephaly, clinical, X-ray and MRI follow-up study of two Albanian siblings aged 8 and 11 years, were made. Both siblings had primary microcephaly, seizures and mild-to-moderate mental retardation. At head imaging the boy was found to have skull asymmetry, partial lack of frontal lobe development and partial agenesis of corpus callosum and the girl had a complex brain malformation consisting in thickening of the fronto-temporal cortex, colpocephaly, increased curvature of the Sylvian fissure, elevated tentorium with mild hypoplasia of the cerebellar vermis and dilated cisterna magna. In addition, the brother had ADHD and the sister minor eye anomalies mainly consisting in epicanthic folds and pale bilateral (temporal) optic disk. We recorded (and documented for the first time by brain MRI) a second family with familial co-occurrence of LCPD and microcephaly and the first occurrence of complex brain anomalies in the context of a small head circumference. The present report could encourage the observation of similar cases. [ABSTRACT FROM AUTHOR]