Extrapyramidal Features Research Articles

A clinical profile of 100 patients with ataxia telangiectasia seen at a tertiary care center

INTRODUCTION: Ataxia telangiectasia (AT) is an autosomal-recessive disease, characterized by progressive cerebellar degeneration, mucocutaneous telangiectasia, immunodeficiency, recurrent sinopulmonary infections, sensitivity to radiation, and increased risk of malignancy. The objective of this study was to report the clinical profile of a large cohort of patients with AT seen in a tertiary care referral center. METHODS: This study was a chart review of 100 patients with AT seen by the department of neurology at the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India, which is a tertiary care referral center. Detailed demographic, clinical, laboratory, and electrophysiological data were collected from the case records. RESULTS: The mean age of presentation was 9.04 ± 3.52 years. Females (n = 40) had earlier age of presentation (8.87 ± 3.09 years) when compared to males (9.15 ± 3.80 years). The mean age for onset of illness was 3.9 ± 2.84 years, and the mean duration of illness was 4.81 ± 3.30 years. A positive family history was obtained in 20% and consanguinity in 60%. Oculomotor abnormalities included impaired pursuit and slow saccades in 60%, oculomotor apraxia in 84%, and nystagmus in 23%. All the patients had cerebellar ataxia. Extrapyramidal features such as dystonia, choreoathetosis, tremors, and myoclonus were observed in 31% of patients. CONCLUSION: Progressive cerebellar ataxia and telangiectasias were the consistent findings observed in all our patients. Dystonia and chorea were the other extrapyramidal features observed. Owing to increased risk of malignancies, screening should be an integral part of management.

Phenotypic and genetic spectrum of SCN8A-related disorders, treatment options, and outcomes.

Pathogenic variants in SCN8A have originally been described in patients with developmental and epileptic encephalopathy (DEE). However, recent studies have shown that SCN8A variants can be associated with a broader phenotypic spectrum, including the following: (1) Patients with early onset, severe DEE, developing severe cognitive and motor regression, pyramidal/extrapyramidal signs, and cortical blindness. Severe SCN8A-DEE is characterized by intractable seizures beginning in the first months of life. The seizures are often prolonged focal hypomotor and occur in clusters, with prominent vegetative symptoms (apnea, cyanosis, mydriasis), evolving to clonic or bilateral tonic-clonic manifestations. Spasm-like episodes, cortical myoclonus, and recurrent episodes of status epilepticus are also common. Electroencephalograms (EEGs) show progressive background deterioration and multifocal abnormalities, predominant in the posterior regions. (2) Sporadic and familial patients with mild-to-moderate intellectual disability, discrete neurological signs, and treatable epilepsy. EEG is abnormal in half of the cases, showing multifocal or diffuse epileptiform abnormalities. (3) Familial cases with benign infantile seizures, sometimes associated with paroxysmal dyskinesia later in life, with no other neurological deficits, normal cognition, and usually normal interictal EEG. (4) Patients without epilepsy but with cognitive and/or behavioral disturbances, or with movement disorders. Extrapyramidal features, such as dyskinesia, ataxia, and choreoathetosis are common in all groups. Early death has been reported in about 5% of the patients, most often in the subgroup of severe DEE. Premature death occurs during early childhood and often for causes other than sudden unexpected death in epilepsy. All epilepsy subgroups exhibit better seizure control with sodium channel blockers, usually at supratherapeutic doses in the severe cases. In severe SCN8A-DEE, ketogenic diet often has a good effect, whereas levetiracetam has a negative effect, if any. The familial SCN8A-related epilepsies show an autosomal dominant pattern of inheritance, whereas the vast majority of SCN8A-DEEs occur de novo.

Cerebellar cognitive-affective syndrome preceding ataxia associated with complex extrapyramidal features in a Turkish SCA48 family.

SCA48 is a novel spinocerebellar ataxia (SCA) originally and recently characterized by prominent cerebellar cognitive-affective syndrome (CCAS) and late-onset ataxia caused by mutations on the STUB1 gene. Here, we report the first SCA48 case from Turkey with novel clinical features and diffusion tensor imaging (DTI) findings, used for the first time to evaluate a SCA48 patient. A 65-year-old female patient with slowly progressive cerebellar ataxia, cognitive impairment, behavioral changes, and a vertical family history was evaluated. Following the exclusion of repeat expansion ataxias, whole exome sequencing (WES) was performed. Brain magnetic resonance imaging (MRI), including DTI, and single-photon emission computed tomography (SPECT) were used to study the primarily affected tracts and regions. WES revealed the previously reported heterozygous truncating mutation in ubiquitin ligase domain of STUB1 (ENST00000219548:c.823_824delCT, ENSP00000219548:p.L275Dfs*16) leading to a frameshift. Patient's cognitive status was compatible with CCAS. Novel clinical features different from the original report include later onset chorea, dystonia, general slowness of movements, apraxia, and palilalia, some of which have been recently reported in two families with different STUB1 mutations. CCAS is a prominent and often early feature of SCA48 which may be followed years after the onset of the disease by other complex neurological signs and symptoms. DTI may be helpful for demonstrating the cerebello-frontal tracts, involved in CCAS-associated SCA48, the differential diagnosis of which may be challenging especially in its early years.

Coexistence of autoimmune antibody-NMDA and paraneoplastic antibody anti-Hu in a patient with behavioral, sensory, motor, cerebellar and extrapyramidal features – A rare case report

Coexistence of autoimmune antibody-NMDA and paraneoplastic antibody anti-Hu in a patient with behavioral, sensory, motor, cerebellar and extrapyramidal features – A rare case report

Progressive myelopathy in an adult

A 55-year-old man reported progressive unsteadiness affecting both legs for 2 years. He dragged both feet while walking and felt the right leg was weaker than the left. He had...

STXBP1 encephalopathy: Connecting neurodevelopmental disorders with α-synucleinopathies?

De novo pathogenic variants in STXBP1 encoding syntaxin1-binding protein (STXBP1, also known as Munc18-1) lead to a range of early-onset neurocognitive conditions, most commonly early infantile epileptic encephalopathy type 4 (EIEE4, also called STXBP1 encephalopathy), a severe form of epilepsy associated with developmental delay/intellectual disability. Other neurologic features include autism spectrum disorder and movement disorders. The progression of neurologic symptoms has been reported in a few older affected individuals, with the appearance of extrapyramidal features, reminiscent of early onset parkinsonism. Understanding the pathologic process is critical to improving therapies, as currently available antiepileptic drugs have shown limited success in controlling seizures in EIEE4 and there is no precision medication approach for the other neurologic features of the disorder. Basic research shows that genetic knockout of STXBP1 or other presynaptic proteins of the exocytic machinery leads to widespread perinatal neurodegeneration. The mechanism that regulates this effect is under scrutiny but shares intriguing hallmarks with classical neurodegenerative diseases, albeit appearing early during brain development. Most critically, recent evidence has revealed that STXBP1 controls the self-replicating aggregation of α-synuclein, a presynaptic protein involved in various neurodegenerative diseases that are collectively known as synucleinopathies, including Parkinson disease. In this review, we examine the tantalizing link among STXBP1 function, EIEE, and the neurodegenerative synucleinopathies, and suggest that neural development in EIEE could be further affected by concurrent synucleinopathic mechanisms.

Amitriptyline induced Acute Dyskinesia

Overall prevalence of tricyclic antidepressants (TCA’s) causing extra-pyramidal features are low. Amongst them acute dyskinesia is not a commonly seen clinical presentation. Here, I describe a case of acute dyskinesia induced by amitriptyline. The challenges in the diagnosis and management are discussed.

Spinocerebellar ataxia 48 presenting with ataxia associated with cognitive, psychiatric, and extrapyramidal features: A report of two Italian families

IntroductionSpinocerebellar ataxia 48 has recently been described as an adult onset ataxia associated with a cerebellar cognitive affective syndrome, caused by a heterozygous mutation in the STUB1 gene. MethodsWe characterized the clinical and neuroimaging phenotype of eight patients from two autosomal dominant ataxia multigenerational Italian families, in whom we conducted whole exome sequencing, targeted multigene sequencing, and Sanger sequencing studies. ResultsWe describe a complex syndrome characterized by ataxia and cognitive-psychiatric disorder in all cases, variably associated with chorea, parkinsonism, dystonia, urinary symptoms, and epilepsy. MRI showed a significant cerebellar atrophy, coupled to a T2-weighted hyperintensity affecting the dentate nuclei and extending to the middle cerebellar peduncles, whereas FDG-PET studies revealed glucose hypometabolism in cerebellum, striatum, and cerebral cortex.We identified two different novel STUB1 mutations segregating in the two families. One of the two mutations, p.(Gly33Ser), occurs in the TRP domain, whereas p.(Pro228Ser) is located in the ubiquitin ligase region. DiscussionWe emphasize the similarity of the described clinical picture with that of SCAR16, an autosomal recessive ataxia caused by biallelic mutations in the same gene, and of spinocerebellar ataxia type 17, which is considered the main Huntington's disease-like syndrome. The pathogenesis of the disease and the relationship between SCA48 and SCAR16 remain to be clarified.

Phenotype-genotype discrepancies in the prospective Huntington at-risk observational study.

ObjectiveTo examine phenotype–genotype discrepancies (PGDs) wherein genotype‐concealed and prospective judgments of the motor onset of Huntington disease (HD) occurred among at‐risk adults who had nonexpanded (<37) cytosine–adenine–guanine (CAG) trinucleotide DNA repeats.MethodsWe examined the prospective clinical assessments of investigators who were kept unaware of individual CAG lengths in the Prospective Huntington At‐Risk Observational Study (PHAROS) who enrolled and followed undiagnosed adults at risk for HD who chose not to learn their gene status. Subjects (n = 1001) at 43 Huntington Study Group research sites in the US and Canada were evaluated prospectively and systematically between 1999 and 2009. At each site, an investigator was designated to perform comprehensive clinic assessments and another investigator to rate only the motor examination. Phenoconversion from a “premanifest” status to a confidently “manifest” status was based on investigator judgment (diagnostic confidence level) of the extrapyramidal motor features of HD.ResultsThere were 20 PGDs that over time had less severe motor scores than the 101 phenoconversions with CAG ≥37, but more severe motor scores than nonconversions. Following conversion, subjects with CAG ≥37 expansions worsened more motorically and cognitively than PGD subjects in the < 37 group. PGDs were concentrated among three sites and a few investigators, especially raters who only assessed the motor examination.InterpretationThe ability to detect the clinical onset of HD in a timely and reliable fashion remains the key for developing experimental treatments aimed at postponing the clinical onset of HD. Comprehensive clinical evaluation is a more accurate and reliable basis for determining HD clinical onset than sole reliance on judging the extrapyramidal features of HD.

Genotype, extrapyramidal features, and severity of variant ataxia-telangiectasia.

ObjectiveVariant ataxia‐telangiectasia is caused by mutations that allow some retained ataxia telangiectasia‐mutated (ATM) kinase activity. Here, we describe the clinical features of the largest established cohort of individuals with variant ataxia‐telangiectasia and explore genotype‐phenotype correlations.MethodsCross‐sectional data were collected retrospectively. Patients were classified as variant ataxia‐telangiectasia based on retained ATM kinase activity.ResultsThe study includes 57 individuals. Mean age at assessment was 37.5 years. Most had their first symptoms by age 10 (81%). There was a diagnostic delay of more than 10 years in 68% and more than 20 years in one third of probands. Disease severity was mild in one third of patients, and 43% were still ambulant 20 years after disease onset. Only one third had predominant ataxia, and 18% had a pure extrapyramidal presentation. Individuals with extrapyramidal presentations had milder neurological disease severity. There were no significant respiratory or immunological complications, but 25% of individuals had a history of malignancy. Missense mutations were associated with milder neurological disease severity, but with a higher risk of malignancy, compared to leaky splice site mutations.InterpretationIndividuals with variant ataxia‐telangiectasia require malignancy surveillance and tailored management. However, our data suggest the condition may sometimes be mis‐ or underdiagnosed because of atypical features, including exclusive extrapyramidal symptoms, normal eye movements, and normal alpha‐fetoprotein levels in some individuals. Missense mutations are associated with milder neurological presentations, but a particularly high malignancy risk, and it is important for clinicians to be aware of these phenotypes. ANN NEUROL 2019;85:170–180.

Clinical and neuropathological phenotype associated with the novel V189I mutation in the prion protein gene

Prion diseases are neurodegenerative disorders which are caused by an accumulation of the abnormal, misfolded prion protein known as scrapie prion protein (PrPSc). These disorders are unique as they occur as sporadic, genetic and acquired forms. Sporadic Creutzfeldt-Jakob Disease (CJD) is the most common human prion disease, accounting for approximately 85–90% of cases, whereas autosomal dominant genetic forms, due to mutations in the prion protein gene (PRNP), account for 10–15% of cases. Genetic forms show a striking variability in their clinical and neuropathological picture and can sometimes mimic other neurodegenerative diseases.We report a novel PRNP mutation (V189I) in four CJD patients from three unrelated pedigrees. In three patients, the clinical features were typical for CJD and the diagnosis was pathologically confirmed, while the fourth patient presented with a complex phenotype including rapidly progressive dementia, behavioral abnormalities, ataxia and extrapyramidal features, and the diagnosis was probable CJD by current criteria, on the basis of PrPSc detection in CSF by Real Time Quaking-Induced Conversion assay. In all the three patients with autopsy findings, the neuropathological analysis revealed diffuse synaptic type deposition of proteinase K-resistant prion protein (PrPres), and type 1 PrPres was identified in the brain by western blot analysis. So, the histopathological and biochemical profile associated with the V189I mutation was indistinguishable from the MM1/MV1 subtype of sporadic CJD.Our findings support a pathogenic role for the V189I PRNP variant, confirm the heterogeneity of the clinical phenotypes associated to PRNP mutations and highlight the importance of PrPSc detection assays as diagnostic tools to unveil prion diseases presenting with atypical phenotypes.

Interesting MRI finding in SSPE – a case report

Introduction: 10% of the subacute sclerosing panencephalitis (SSPE) presents with atypical features. Aim: SSPE is rare chronic encephalitis caused by persistent infection with defective measles virus. Characteristic MRI findings include signal changes (T2W and FLAIR hyperintensities) in bilateral occipital and parietal regions involving both gray and white matter. Early involvement of cerebellum and brainstem is not common. Case study: A 17-year-old male presented with complaints of recurrent seizures, slow walking, and behavioral abnormality. Neurological examination revealed cogwheel rigidity in all four limbs. MRI of the brain revealed asymmetrical cortical and subcortical altered signal intensities (T2W and FLAIR hyperintensity and T1W hypointensity) involving temporal and occipital lobes bilaterally (left more than right) with diffuse atrophy of cerebrum and cerebellum. Results and discussion: Early onset extrapyramidal features, seizures without myoclonus with MRI finding of posterior predominant asymmetrical cortical and subcortical signal abnormality is uncommon in SSPE. Conclusions: A high index of clinical suspicion for SSPE has to be maintained in patients haling from endemic areas, unvaccinated individuals presenting with seizures, behavioral abnormality, and extrapyramidal features.

Efficiency of Transcranial Magnetic Stimulation in Progressive Supranuclear Palsy: Estimation Using Goniometry and Dinamometry

Progressive supranuclear palsy (PSP) is a degenerative movement disorder involving gradual deterioration and death of specific brain areas. Extrapyramidal features (losing balance, frequent falls, and paralysis of vertical gaze) make daily life difficult for the individual. Novel rehabilitation techniques complementary to human or robotic rehabilitation methods in such cases are emerging. Repetitive transcranial magnetic stimulation (rTMS) is such a tool, which began to be used in the rehabilitation of motor disorders. We observed positive effects of rTMS (over the motor cortex area, 1.0 sec–1, 20 min per day, for 5 days) on the motor functions in a PSP case using a mechanography approach (pre- and post-treatment goniometry and dynamometry). The respective measurements showed that rTMS led to noticeable increases in the angles of most tested movements of the upper and lower limbs of the patient and in the forces developed during such movements.

Hyperargininemia Experiences over Last 7 Years from a Tertiary Care Center.

Context:Several Enzymes carry out chemical reactions for the production of energy and carrying out normal functioning of the organism. Disorders of these functions can result in permanent damage to the child affecting multiple systems. Most metabolic disorders are at least controllable and therefore it is important to recognize them early for ensuring optimum growth and development. This involves proper pattern recognition by the clinician.Aims:In this study we are discussing a rare treatable metabolic disorder namely Hyperargininemia seen by the authors in the last seven years.Settings and Design:Various parameters of confirmed hyperargininemia patients were analysed.Methods and Material:It is a descriptive study where all patients were confirmed cases with red blood cell arginase levels <10.Statistical Analysis used:Descriptive statistical analysis, Mann-whitney test, spearman’s rho.Results:In this study we found consanguinity in 30 % of patients. At least one sibling was affected in 13 % of patients. Females were more in this group though the pattern remains AR. Symptom onset showed variability from less than 1 year to up to 17 years. Commonest clinical feature was cognitive dysfunction, spasticity, seizures, microcephaly and lesser number with extrapyramidal and cerebellar features. Failure to thrive and dysmorphic features were also seen.Conclusion:Hyperargininemia commonly manifests as regression, failure to thrive, spasticity, seizures with or without microcephaly. When the above phenotype is seen, it is mandatory to screen for urea cycle disorders.

Trajectories of motor abnormalities in milder phenotypes of ataxia telangiectasia

To describe and classify the neurologic trajectories in patients with mild neurologic forms of ataxia telangiectasia (A-T) from the Dutch A-T cohort, combined with patients reported in the literature. Clinical, genetic, and laboratory data of 14 patients with mild neurologic phenotypes of A-T from the Dutch cohort were analyzed and combined with corresponding data from the literature. A mild neurologic phenotype was defined by a later onset, nonataxia presenting or dominant feature, or slower progression compared to the classic A-T phenotype. Neurologic trajectories were classified based on age at onset, presenting feature, and follow-up data. One hundred five patients were included in the study. Neurologic trajectories were categorized into 6 groups: patients with childhood-onset extrapyramidal (EP) features with cerebellar symptoms developing later (group 1; 18 patients), childhood-onset cerebellar symptoms, with EP features developing later (group 2; 35 patients), childhood- to adolescence-onset dystonia, without cerebellar symptoms (group 3; 23 patients), childhood- to adolescence-onset isolated cerebellar symptoms (group 4; 22 patients), childhood- to adult-onset prominent muscle weakness (group 5; 2 patients), and patients with adult-onset EP features, with anterior horn cell disease arising subsequently (group 6; 5 patients). This systematic study of the different motor abnormalities and their course over time in patients with mild phenotypes of A-T, enabled us to recognize 6 essentially different phenotypic patterns. Awareness of these different trajectories of motor abnormalities in milder forms of A-T will contribute to a reduction of diagnostic delay in this severe multisystem disorder.

Flunarizine for Headache Prophylaxis in Children With Sturge-Weber Syndrome

BackgroundChildren with Sturge-Weber syndrome can experience severe headache with or without transient hemiparesis. Flunarizine, a calcium antagonist, has been used for migraine. The experience with flunarizine for headache in a cohort of children at a national center for Sturge-Weber syndrome is reviewed, reporting its efficacy and adverse effect in this population. MethodsWe collected data from health care professionals' documentation on headache (severity, frequency, duration) before and on flunarizine in 20 children with Sturge-Weber syndrome. Adverse effects reported during flunarizine treatment were collated. The Wilcoxon signed rank test was used to determine the significance of pre- versus post-treatment effect. ResultsFlunarizine was used for headache alone (13) or mixed migrainous episodes and vascular events (7). The median duration of treatment was 145 days (range 43 to 1864 days). Flunarizine reduced headache severity (z = −3.354, P = 0.001), monthly frequency (z = −2.585, P = 0.01), and duration (z = −2.549, P = 0.01). Flunarizine was discontinued owing to intolerable adverse effects in a minority (2). Sedation and weight gain were the most common side effects. There were no reports of behavior change or extrapyramidal features. ConclusionsThe most effective management for headaches in patients with Sturge-Weber syndrome has not been established. This retrospective observational study found benefit of flunarizine prophylaxis on headache severity, frequency, and duration in children with Sturge-Weber syndrome without severe side effects. Flunarizine is not licensed for use in the United Kingdom, but these data support its off-license specialist use for headache prophylaxis in Sturge-Weber syndrome.

Non-ataxic manifestations of Spinocerebellar ataxia-2, their determinants and predictors

IntroductionTo evaluate the non-ataxic clinical manifestations in genetically proven Spinocerebellar ataxia 2 (SCA2) and identify their determinants and predictors. MethodsSeventy-three subjects with genetically proven SCA2 were evaluated clinically for the common non-ataxic manifestations. Based on the presence or absence of non-ataxic manifestations, patients were classified into groups and then compared for significant differences in the CAG repeat length, age at onset (AAO), duration of disease, and ataxia rating score. Predictors of non-ataxic symptoms were identified using multivariable binary logistic regression. ResultsThe most common non-ataxic clinical manifestations were peripheral neuropathy, extrapyramidal features, pyramidal signs, cognitive impairment and lower motor neuron signs. The CAG repeat length was inversely related to the AAO of symptoms (r = −0.46, p < .001). Patients with peripheral neuropathy and psychiatric symptoms had earlier AAO. Patients with cognitive impairment and extrapyramidal symptoms had higher CAG repeat length whereas presence of lower motor neuron signs was more common in patients with lower CAG repeat length. ConclusionThe lower strength of association between CAG repeat length and AAO in our cohort suggests the presence of additional factors underlying the variability in AAO. Both CAG repeat length and AAO were identified as significant determinants and predictors of non-ataxic symptoms.

Wilson Disease with Hepatic Impairment and Thrombocytopenia: A Case Report

: Introduction: Wilson disease is a rare autosomal recessive disorder. The Case report describes the penicillamine induced thrombocytopenia. Case Report: A 14-year-old girl presented with previously diagnosed with Wilson disease treated with penicillamine and pyridoxine. Complaints of dyskinesia, slurred speech, severe hyperbilirubinemia and prominent extrapyramidal features consisting of the rigidity, tremors and ophthalmic examination of her eyes reveal the Kayser-Fleischer ring and sunflower cataract and low blood count. Conclusion: Wilson disease is a rare inherited disorder. Approximately 30% of the patient cannot tolerate penicillamine due to early hypersensitivity or bone marrow suppression or renal failure occurs due to the failure of therapy. Hence zinc is considered an alternative therapy for pediatric patients.Key words: Wilson disease, thrombocytopenia, hepatic impairment, penicillamine, zinc

Extrapyramidal deficits in ALS: a combined biomechanical and neuroimaging study.

Extrapyramidal deficits are poorly characterised in amyotrophic lateral sclerosis (ALS) despite their contribution to functional disability, increased fall risk and their quality-of-life implications. Given the concomitant pyramidal and cerebellar degeneration in ALS, the clinical assessment of extrapyramidal features is particularly challenging. The comprehensive characterisationof postural instability in ALS using standardised clinical assessments, gait analyses and computational neuroimaging tools in a prospective study design. Parameters of gait initiation in the anticipatory postural adjustment phase (APA) and execution phase (EP) were evaluated in ALS patients with and without postural instability and healthy controls. Clinical and gait analysis parameters were interpreted in the context of brain imaging findings. ALS patients with postural instability exhibit impaired gait initiation with an altered APA phase, poor dynamic postural control and significantly decreased braking index. Consistent with their clinical profile, "unsteady" ALS patients have reduced caudate and brain stem volumes compared to "steady" ALS patients. Our findings highlight that the ALS functional rating scale (ALSFRS-r) does not account for extrapyramidal deficits, which are major contributors to gait impairment in a subset of ALS patients. Basal ganglia degeneration in ALS does not only contribute to cognitive and behavioural deficits, but also adds to the heterogeneity of motor disability.

Expanding spectrum of RARS2 gene disorders: Myoclonic epilepsy, mental retardation, spasticity, and extrapyramidal features.

SummaryPontocerebellar hypoplasia type 6 (PCH6) is an autosomal recessive mitochondrial disease, typically characterized by pontine atrophy, vermian hypoplasia, infantile encephalopathy, generalized hypotonia, and intractable seizures. The purpose of this study is to describe the seizures and other neurological manifestations of RARS2 gene mutations and to compare the clinical features with other causes of progressive myoclonic epilepsy. Detailed history, physical examination, and clinical and genetic work‐up were performed in 2 siblings who presented with progressive myoclonic epilepsy. One sibling, a 20‐year‐old woman, and the other a 24‐year‐old man, had a homozygous missense variant (c.848T>A; p.Leu283Gln) in exon 10 of the RARS2 gene. The female patient had action and audiogenic myoclonic jerks, postural tremors, spastic dysarthria, and bradykinesia, and her male sibling had similar features with oculomotor apraxia. The RARS2 gene mutation can present with myoclonic epilepsy, mental retardation, and pyramidal and extrapyramidal features, and is an important differential for causes of progressive myoclonic epilepsy.