Three sporadic patients (two men and one woman) were examined with involuntary movements and dysarthria associated with abnormal concentrations of serum copper, serum ceruloplasmin, and urinary copper excretion.
Three factors (F1-F3) characterized the clinical outcome (F1: tremor and pathological reflexes; F2: dystonia and dysarthria; F3: cerebellar abnormalities and gait), and three factors the laboratory findings (LF1: serum level of ceruloplasmin; LF2: liver enzymes; LF3: INR).
We report here on the characterization of a mutation in the ceruloplasmin gene in a 45 year old woman with insulin-dependent diabetes mellitus who presented with the recent onset of gait disturbance and dysarthria.
A four-generation pedigree exhibiting early-onset autosomal dominant Alzheimer disease (AD) with spastic paraplegia, dystonia, and dysarthria due to a novel 6-nucleotide insertional mutation in exon 3 of the presenilin 1 gene (PS1) is described.
We describe an atypical case of pantothenate kinase-associated neurodegeneration (PKAN) in which slowly progressive arm tremor was the predominant symptom beginning at the age of 25, with late-onset dystonia and dysarthria developing at the age of 50.
The presence of mutation in the PANK2 gene is associated with younger age at onset and a higher frequency of dystonia, dysarthria, intellectual impairment, and gait disturbance.
Through scanning the exons and flanking intronic sequences of PANK2 in patient and control subjects, we report a compound heterozygote c. 260A > G (NM_001324191) and c.405dupC (NM_153638) for PANK2 mutations in a Chinese patient with clinical manifestation of progressive prosopospasm, dysarthria and gait disturbance.
Snyder-Robinson syndrome is a rare form of X-linked intellectual disability caused by mutations in the spermine synthase (SMS) gene, and characterized by intellectual disability, thin habitus with diminished muscle mass, osteoporosis, kyphoscoliosis, facial dysmorphism (asymmetry, full lower lip), long great toes, and nasal or dysarthric speech.
Distinctive features of dysarthria and dyspraxia are found in individuals with GRIN2A mutations, often in the setting of epilepsy-aphasia syndromes; dysarthria has not been previously recognized in these disorders.
Mutations in the polymerase gamma-1 (POLG1) gene, encoding the catalytic subunit of the mtDNA-specific polymerase-γ, compromise the stability of mitochondrial DNA (mtDNA) and are responsible for numerous clinical presentations as autosomal dominant or recessive progressive external ophthalmoplegia (PEO), sensory ataxia, neuropathy, dysarthria and ophthalmoparesis (SANDO), spinocerebellar ataxia with epilepsy (SCAE) and Alpers syndrome.
All affected members present with cognitive impairment and two of them with mild intermittent involuntary movements in association with the clinical hallmarks of SCA15 (gait ataxia, balance impairment, and dysarthria).
We identified a novel c.260T > C, p.(Leu87Pro)XPR1 variant in a 41-year-old man complaining of micrographia and dysarthria and demonstrating mild parkinsonism, cerebellar ataxia and executive dysfunction.
The mutation in UBQLN2 was first identified in a 35-year-old female who presented with one year of progressive dysarthria, dyspnea, dysphagia, and cognitive decline.
Autosomal dominant transmission of mutations of NKX2-1 may cause congenital hypothyroidism, neonatal respiratory distress at term, and persistent neurologic findings such as ataxia, choreoathetosis, and dysarthria in families with affected subjects in multiple generations.
In contrast, the only two missense mutations located in the amino-terminal half of mature frataxin (D122Y and G130V) cause an atypical and milder clinical presentation (early-onset spastic gait with slow disease progression, absence of dysarthria, retained or brisk tendon reflexes, and mild or no cerebellar ataxia), suggesting that they only partially affect frataxin function.
Our data, with previously published reports, suggest that duplications involving SHROOM4 and DGKK may represent a new syndromic X-linked ID critical region associated with mild to severe ID, speech delay +/- dysarthria, attention deficit disorder, precocious puberty, constipation, and motor delay.