Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a 64-year-old woman, suffering from late-onset obsessive-compulsive disorder (OCD) from the age of 57, who developed dysarthria and dysphagia, spastic diplegic, and proximal muscles weakness. Needle electromyography showed no active denervation. Neuropsychological evaluation showed intact cognitive functioning. We diagnosed upper motor neuron disease (MND), with no known genetic correlates. Brain magnetic resonance (MRI) detected bilateral hippocampal atrophy with sclerosis of right hippocampus. 18F-FDG positron emission tomography (PET) showed moderate right temporal cortex thinning. Six months later, motor and behavioral symptoms worsened. Neuropsychological examination revealed long-term memory deficit and executive dysfunction. MRI and PET evidenced severe worsening of atrophy in temporal and frontal lobes. Four years later a definitive diagnosis of primary lateral sclerosis (PLS) and FTD was made. To our knowledge, this is the first report of PLS and FTD with OCD at onset.
 ...
PMID:A case of late-onset OCD developing PLS and FTD. 2945 Oct 27

Primary lateral sclerosis (PLS) is a rare neurodegenerative disorder at the upper motor neurone extreme of the spectrum of motor neurone disease. The diagnosis is clinical and based on the characteristic features of slowly progressive spasticity beginning in the lower limbs, or more rarely with spastic dysarthria, typically presenting around 50 years of age. The absence of lower motor neurone involvement is considered to be a defining feature, but confident distinction of PLS from upper motor neurone-predominant forms of amyotrophic lateral sclerosis may be difficult in the first few years. Corticobulbar involvement in PLS is frequently accompanied by emotionality. While there may be dysphagia, gastrostomy is rarely required to maintain nutrition. Cognitive dysfunction is recognised, though dementia is rarely a prominent management issue. PLS is not necessarily life shortening. Specialised multidisciplinary care is recommended. Increasing international research cooperation is required if the aspiration of dedicated therapeutic trials for PLS is to be achieved.
 ...
PMID:Primary lateral sclerosis: diagnosis and management. 3221 63

Autosomal-recessive mutations in the Alsin Rho guanine nucleotide exchange factor (ALS2) gene may cause specific subtypes of childhood-onset progressive neurodegenerative motor neuron diseases (MND). These diseases can manifest with a clinical continuum from infantile ascending hereditary spastic paraplegia (IAHSP) to juvenile-onset forms with or without lower motor neuron involvement, the juvenile primary lateral sclerosis (JPLS) and the juvenile amyotrophic lateral sclerosis (JALS). We report 11 patients from seven unrelated Turkish and Yemeni families with clinical signs of IAHSP or JPLS. We performed haplotype analysis or next-generation panel sequencing followed by Sanger Sequencing to unravel the genetic disease cause. We described their clinical phenotype and analyzed the pathogenicity of the detected variants with bioinformatics tools. We further reviewed all previously reported cases with ALS2-related MND. We identified five novel homozygous pathogenic variants in ALS2 at various positions: c.275_276delAT (p.Tyr92CysfsTer11), c.1044C>G (p.Tyr348Ter), c.1718C>A (p.Ala573Glu), c.3161T>C (p.Leu1054Pro), and c.1471+1G>A (NM_020919.3, NP_065970.2). In our cohort, disease onset was in infancy or early childhood with rapid onset of motor neuron signs. Muscle weakness, spasticity, severe dysarthria, dysphagia, and facial weakness were common features in the first decade of life. Frameshift and nonsense mutations clustered in the N-terminal Alsin domains are most prevalent. We enriched the mutational spectrum of ALS2-related disorders with five novel pathogenic variants. Our study indicates a high detection rate of ALS2 mutations in patients with a clinically well-characterized early onset MND. Intrafamilial and even interfamilial diversity in patients with identical pathogenic variants suggest yet unknown modifiers for phenotypic expression.
 ...
PMID:Genotype-phenotype correlation in seven motor neuron disease families with novel ALS2 mutations. 3315 58


<< Previous 1 2