The Diagnostic Challenge of Frontal Alzheimer's Disease: Case Report and Literature Review

Atypical forms of Alzheimer's disease (AD) have long been described, but it's only recently that the aphasic, frontal, and visuospatial variants have been included in the clinical diagnostic and research criteria for AD. The frontal form, also known as the behavioral and/or dysexecutive form of AD, is still a poorly understood and poorly defined entity. Patients present with either behavioral or executive disorders, or both. It is now possible to establish, in vivo, a diagnosis of frontal variant AD (fv-AD) with a high degree of probability by comparing the neuropsychological profile and biomarkers. However, the neuropsychological and behavioral profile of patients with fv-AD is still poorly understood, often leading to diagnostic difficulties and confusion with the behavioral variant of frontotemporal lobar degeneration (bv-FTLD), which is the main differential diagnosis. We will illustrate the difficulties sometimes encountered in practice in the differential diagnosis between these pathologies through a clinical observation

A riboflavin-responsive neuronopathy with unique characteristics: Brown-Vialetto- Van Laere syndrome

Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare disease characterized by progressiveaxonal neuropathy, optic atrophy, hearing loss, bulbar dysfunction, and respiratoryfailure associated with mutations in the SLC52A2 and SLC52A3 genes thatcode for the human riboflavin transporters RFVT2 and RFVT3, respectively. Nearly70 cases have been reported by molecular diagnosis. The majority of familial casesare autosomal recessive, with a female to male ratio of 3:1. We describe the clinicalcase of a 14 years-old boy with BVVLS who presented from a young age withprogressive sensorineural hearing loss of insidious onset, followed by atrophy of thetongue with fasciculations. Sometimes the clinical spectrum mimics juvenile-onsetmotor neuron disease (MND). It is important to identify BVVLS that may respond tohigh doses of riboflavin

Adult-onset vanishing white matter disease presenting as dementia

Vanishing White Matter Disease (VWMD), also known as Childhood Ataxia with Central Hypomyelination (CACH) is a leukoencephalopathy with an autosomal recessive inheritance. It is caused by mutations in any of the five genes encoding the five subunits of the eukaryotic translational initiation factor 2B (eIF2B). Although VWMD was initially described in young children, it is now well known that it has a wide phenotypic spectrum, affecting people of all ages.VWMD is typically characterized by normal or mildly delayed initial psychomotor development, followed by episodic or chronic neurological deterioration, often provoked by infections or minor head trauma. Neurological signs consist mainly of cerebellar ataxia and spasticity. There is no specific treatment beside the “prevention” of cellular stress. Therefore, early recognition of the diagnosis is important to avoid triggering factors and allow genetic counseling.The reported case describes the clinical and radiological characteristics of a patient with adulthood onset of VWMD, revealed by subcortical dementia.</p

Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries

Objective Genetic diagnosis and mutation identification are now compulsory for Duchenne (DMD) and Becker muscular dystrophies (BMD), which are due to dystrophin (DMD) gene mutations, either for disease prevention or personalized therapies. To evaluate the ethnic-related genetic assortments of DMD mutations, which may impact on DMD genetic diagnosis pipelines, we studied 328 patients with DMD and BMD from non-European countries. Methods We performed a full DMD mutation detection in 328 patients from 10 Eastern European countries (Poland, Hungary, Lithuania, Romania, Serbia, Croatia, Bosnia, Bulgaria, Ukraine,and Russia) and 2 non-European countries (Cyprus and Algeria). We used both conventional methods (multiplex ligation-dependent probe amplification [MLPA] followed by gene-specific sequencing) and whole-exome sequencing (WES) as a pivotal study ran in 28 patients where DMD mutations were already identified by standard techniques. WES output was also in-terrogated forDMDgene modifiers. Results We identified DMD gene mutations in 222 male patients. We identified a remarkable allele heterogeneity among different populations with a mutation landscape often country specific. We also showed that WES is effective for picking up all DMD deletions and small mutations and its adoption could allow a detection rate close to 90% of all occurring mutations. Gene modifiers haplotypes were identified with some ethnic-specific configurations. Conclusions Our data provide unreported mutation landscapes in different countries, suggesting that ethnicity may orient genetic diagnosis flowchart, which can be adjusted depending on the mutation type frequency, with impact in drug eligibility