BACKGROUND

 Neuromuscular and movement disorders comprise a heterogeneous group of acquired and inherited conditions affecting the motor unit and central movement pathways. Genetic data from underserved populations, including Filipinos, remain limited, highlighting the need for population-specific characterization.

OBJECTIVE

To characterize inherited neuromuscular and movement disorders among Filipinos and determine the diagnostic yield and genetic spectrum using next-generation sequencing (NGS).

METHODS

This referral single-center retrospective study reviewed Filipino patients who underwent genetic testing for suspected inherited neuromuscular and movement disorders. Variants were classified according to the American College of Medical Genetics and Genomics (ACMG) criteria.

RESULTS

Among 85 patients, 24 (28.2%) had pathogenic/likely pathogenic variants, 33 (38.8%) had variants of uncertain significance (VUS) and 28 (32.9%) were negative. Confirmed diagnoses included pediatric cases of limb-girdle muscular dystrophy, Duchenne muscular dystrophy, spinal muscular atrophy and GNE-related myopathy, and adult cases with myofibrillar myopathy, spinocerebellar ataxia and amyotrophic lateral sclerosis. Pathogenic variants involved 26 genes, most commonly SMN1.

CONCLUSION

This NGS-based characterization of inherited neuromuscular and movement disorders in Filipinos showed 28% diagnostic yield and a spectrum comparable to other Asian cohorts. The high rate of VUS underscores the need for family segregation studies and careful genotype–phenotype correlation. This study highlights the critical role of genetic testing in accurate diagnosis and targeted management to improve outcomes for patients with these rare disorders.

Retrospective Studies ; Referral And Consultation ; Population ; Movement Disorders ; Movement

A 19-year-old female with a 2-day history of involuntary fast jerk-like movements of the left upper and lower extremities presented at the emergency department. Patient had no other known comorbidities and family history was unremarkable. Anti-streptolysin O titer (ASO) and C-reactive protein (CRP) were all normal. Two-dimensional echocardiography (2D Echo) revealed thickened anterior mitral valve leaflet with prolapsed A2 scallop, mild mitral regurgitation, thickened right coronary cusp of aortic valve without restriction of motion, trivial aortic regurgitation, other findings were unremarkable. Patient was managed as a case of Sydenham’s chorea secondary to acute rheumatic fever, with valvular heart disease secondary. Patient was initially started on valproic acid 500mg tablet every 8 hours, benzathine penicillin 1.2M units intramuscular, and carvedilol 12.5mg/tablet twice a day. The patient was then shifted to haloperidol 5mg ¼ tablet twice a day, diphenhydramine 50mg intravenously coinciding with haloperidol doses due to visual side effects of valproic acid. This report highlights the importance of a high index of suspicion and complete history and physical examination in order to diagnose and manage movement disorders in a low-income setting.

Human ; Female ; Young Adult: 19-24 Yrs Old ; Movement Disorders ; Diphenhydramine ; Aortic Valve Insufficiency ; Heart Valve Diseases ; C-reactive Protein

Clinical grading diagnosis of disorder of consciousness (DOC) patients relies on behavioral assessment, which has certain limitations. Combining multi-modal technologies and brain-computer interface (BCI) paradigms can assist in identifying patients with minimally conscious state (MCS) and vegetative state (VS). This study collected electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS) signals under motor BCI paradigms from 14 DOC patients, who were divided into two groups based on clinical scores: 7 in the MCS group and 7 in the VS group. We calculated event-related desynchronization (ERD) and motor decoding accuracy to analyze the effectiveness of motor BCI paradigms in detecting consciousness states. The results showed that the classification accuracies for left-hand and right-hand movement tasks using EEG were 93.28% and 76.19% for the MCS and VS groups, respectively; the classification precisions using fNIRS were 53.72% and 49.11% for these groups. When combining EEG and fNIRS features, the classification accuracies for left-hand and right-hand movement tasks in the MCS and VS groups were 95.56% and 87.38%, respectively. Although there was no statistically significant difference in motor decoding accuracy between the two groups, significant differences in ERD were observed between different consciousness states during left-hand movement tasks ( P < 0.001). This study demonstrates that motor BCI paradigms can assist in assessing the level of consciousness, with EEG being more sensitive for evaluating residual motor intention intensity. Moreover, the ERD feature of motor intention intensity is more sensitive than BCI classification accuracy.
Humans ; Brain-Computer Interfaces ; Spectroscopy, Near-Infrared/methods* ; Electroencephalography/methods* ; Consciousness Disorders/diagnosis* ; Male ; Movement ; Adult ; Female ; Intention ; Persistent Vegetative State/diagnosis*

OBJECTIVES: To summarize the clinical manifestations and genetic characteristics of creatine deficiency syndrome (CDS) caused by GAMT gene mutations. METHODS: A retrospective analysis was conducted on the clinical and genetic data of two children diagnosed with GAMT deficiency-type CDS at the Children's Medical Center of Xiangya Hospital, Central South University, from December 2020 to December 2024. RESULTS: The two patients presented with symptoms in infancy, and both had compound heterozygous mutations in the GAMT gene. Case 1 exhibited seizures and intellectual disability, while Case 2 had intellectual disability and attention-deficit hyperactivity disorder. Magnetic resonance spectroscopy of cranial MRI in both patients indicated reduced creatine peaks. After creatine treatment, seizures in Case 1 were controlled, but both patients continued to experience intellectual disabilities and behavioral issues. As of December 2024, a total of 21 cases have been reported in China (including this study), and 115 cases have been reported abroad. All patients exhibited developmental delay or intellectual disabilities, with 66.9% (91/136) experiencing seizures, 33.8% (46/136) presenting with motor disorders, and 36.8% (50/136) having behavioral problems. Seventy-five percent (102/136) of patients received creatine treatment, leading to significant improvements in seizures and motor disorders, although cognitive improvement was not substantial. CONCLUSIONS GAMT deficiency-type CDS is rare and presents with nonspecific clinical features. Timely diagnosis facilitates targeted treatment, which can partially improve prognosis.
Child ; Female ; Humans ; Male ; Creatine/deficiency* ; Guanidinoacetate N-Methyltransferase/deficiency* ; Intellectual Disability/genetics* ; Mutation ; Retrospective Studies ; Rhabdomyolysis/genetics* ; Language Development Disorders ; Movement Disorders/congenital*

Movement disorder, as a presentation of an acute or chronic cerebrovascular disease (CVD) occur in less than five percent of CVD cases. Although a rare presentation of CVDs, stroke is a common etiology of secondary movement disorder. Hemichorea is particularly prevalent following stroke. The objectives of this report are to (1) present nine cases of sudden-onset hyperkinetic movement disorders manifested in acute and chronic stroke patients (2) emphasize the importance of early diagnosis by clinical signs and symptoms identified through computed tomography (CT) and magnetic resonance imaging (MRI), and (3) determine the different anatomic locations involved in this disorder. Hemichorea is the most common hyperkinetic movement disorder seen after stroke with a predilection in older age. It demonstrated that deep vascular lesions had a greater probability of developing movement disorder. Hemichorea-hemiballismus with abrupt onset should be approached as an acute stroke until other potential causes are ruled out. The exact pathophysiology of these abnormal movements remains unclear, although some theories propose dysfunction within the motor circuitry pathway. While many cases resolve spontaneously, medical or surgical interventions may be necessary to manage symptoms, potentially influencing long-term outcomes.

Human ; Male ; Female ; Aged: 65-79 Yrs Old ; Middle Aged: 45-64 Yrs Old ; Movement Disorders ; Chorea ; Hemiballismus ; Dyskinesias ; Stroke

Movement disorder, as a presentation of an acute or chronic cerebrovascular disease (CVD) occur in less than five percent of CVD cases. Although a rare presentation of CVDs, stroke is a common etiology of secondary movement disorder. Hemichorea is particularly prevalent following stroke. The objectives of this report are to (1) present nine cases of sudden-onset hyperkinetic movement disorders manifested in acute and chronic stroke patients (2) emphasize the importance of early diagnosis by clinical signs and symptoms identified through computed tomography (CT) and magnetic resonance imaging (MRI), and (3) determine the different anatomic locations involved in this disorder. Hemichorea is the most common hyperkinetic movement disorder seen after stroke with a predilection in older age. It demonstrated that deep vascular lesions had a greater probability of developing movement disorder. Hemichorea-hemiballismus with abrupt onset should be approached as an acute stroke until other potential causes are ruled out. The exact pathophysiology of these abnormal movements remains unclear, although some theories propose dysfunction within the motor circuitry pathway. While many cases resolve spontaneously, medical or surgical interventions may be necessary to manage symptoms, potentially influencing long-term outcomes.

Human ; Male ; Female ; Aged: 65-79 Yrs Old ; Middle Aged: 45-64 Yrs Old ; Movement Disorders ; Chorea ; Hemiballismus ; Dyskinesias ; Stroke

Introduction: We present a patient with long-standing uncontrolled type 2 diabetes mellitus (T2 DM) who developed sudden onset of choreiform movement, which rapidly resolved after insulin therapy and haloperidol. Case Description: A 53-year-old Filipino male, with T2DM and hypertension for more than 10 years, presented with sudden onset of hyperkinetic, involuntary, non-patterned, continuous movements of the left upper and lower extremities. Investigations revealed severe hyperglycemia without acidemia and ketonuria. Cranial computed tomography scan showed hyperdensity on the right caudate and lentiform nuclei. On cranial magnetic resonance imaging, there was T1- weighted hyperintense and T2 - weighted hypointense signal involving the right putamen, globus pallidus and caudate. Cranial magnetic resonance angiography showed stenosis on the cavernous segment of the right internal carotid artery (ICA), left ICA and middle cerebral artery (MCA) junction, the A1 segment of the left anterior communicating artery and proximal P2 segments of the bilateral posterior cerebral arteries. The patient was managed with a basal-bolus insulin regimen to control the blood glucose and haloperidol to manage the extrapyramidal symptoms. Consequently, there was complete resolution of the involuntary movements. Conclusion This case illustrates the importance of a systematic approach to movement disorders and early recognition of this rare diabetes complication known as chorea hyperglycemia basal ganglia syndrome or diabetic striatopathy.
Movement Disorders ; Diabetes Complications

Vitamin B12 deficiency has long been known to present with various neurological manifestations, but only rarely presents as movement disorders, especially in adults. We present the case of a 30-year-old vegan male presenting with tremors on both legs when standing which was relieved by vitamin B12 supplementation. To the best of our knowledge, this is the first documented case of slow orthostatic tremor or pseudo-orthostatic tremor caused by vitamin B12 deficiency.
Vitamin B 12 Deficiency ; Vitamin B 12 ; Vegans ; Movement Disorders ; Tremor ; Electromyography

OBJECTIVE: To investigate the effect of miR-22 targeting formin-like protein 2 (FMNL2) on the migration and apoptosis of childhood acute myeloid leukemia (AML) cells. METHOD: Peripheral blood samples from 11 children with AML, 10 children with immune thrombocytopenia, human AML cell lines TF-1a, HL-60, THP-1 and human bone marrow stromal cells HS-5 were used as the research objects. UniCel DxH 800 automatic hematology analyzer detected platelet count, hemoglobin, and white blood cell count in peripheral blood samples, and RT-qPCR detected miR-22 expression in peripheral blood samples and AML cells. HL-60 cells were transfected with Lipofectamine^TM 2000 kit, the experiments were divided into seven groups: blank (no cells transfected), miR-NC, miR-22 mimics, si-NC, si-FMNL2 , miR-22 mimics+OE-NC and miR-22 mimics+OE-FMNL2 . RT-qPCR was used to detect the expression of miR-22 in each group. Transwell was used to detect cell migration. Flow cytometry was used to detect cell apoptosis. Dual-luciferase reporter gene detection experiments verified the targeting relationship between miR-22 and FMNL2 . Western blot was used to detect the expression of FMNL2 protein. RESULTS: Compared with the control group, the number of leukocytes in the peripheral blood of children with AML was significantly increased (P <0.001), while the concentration of hemoglobin and the number of platelets were significantly decreased P <0.001). The expression level of miR-22 in peripheral blood of children with AML was significantly lower than that in control group (P <0.001). Compared with HS-5 cells, the expression levels of miR-22 in TF-1a, HL-60, and THP-1 cells were significantly decreased (P <0.05), and in HL-60 cells was the lowest. Therefore, HL-60 cells were selected for subsequent experiments. Up-regulation of miR-22 or silencing of FMNL2 could reduce the number of migrating cells and increase apoptosis rate (P <0.05). MiR-22 targeted and negatively regulated the expression of FMNL2 . FMNL2 overexpression reversed the effects of up-regulated miR-22 on migration and apoptosis of HL-60 cells. CONCLUSION MiR-22 can inhibit the migration and promote apoptosis of HL-60 cells by down regulating the expression of FMNL2 .
Humans ; Child ; MicroRNAs/metabolism* ; Leukemia, Myeloid, Acute/metabolism* ; Cell Proliferation ; Apoptosis ; Myeloproliferative Disorders ; Cell Movement ; Hemoglobins ; Cell Line, Tumor ; Formins

The radial migration of cortical pyramidal neurons (PNs) during corticogenesis is necessary for establishing a multilayered cerebral cortex. Neuronal migration defects are considered a critical etiology of neurodevelopmental disorders, including autism spectrum disorders (ASDs), schizophrenia, epilepsy, and intellectual disability (ID). TRIO is a high-risk candidate gene for ASDs and ID. However, its role in embryonic radial migration and the etiology of ASDs and ID are not fully understood. In this study, we found that the in vivo conditional knockout or in utero knockout of Trio in excitatory precursors in the neocortex caused aberrant polarity and halted the migration of late-born PNs. Further investigation of the underlying mechanism revealed that the interaction of the Trio N-terminal SH3 domain with Myosin X mediated the adherence of migrating neurons to radial glial fibers through regulating the membrane location of neuronal cadherin (N-cadherin). Also, independent or synergistic overexpression of RAC1 and RHOA showed different phenotypic recoveries of the abnormal neuronal migration by affecting the morphological transition and/or the glial fiber-dependent locomotion. Taken together, our findings clarify a novel mechanism of Trio in regulating N-cadherin cell surface expression via the interaction of Myosin X with its N-terminal SH3 domain. These results suggest the vital roles of the guanine nucleotide exchange factor 1 (GEF1) and GEF2 domains in regulating radial migration by activating their Rho GTPase effectors in both distinct and cooperative manners, which might be associated with the abnormal phenotypes in neurodevelopmental disorders.
Autism Spectrum Disorder/metabolism* ; Cell Movement/genetics* ; Humans ; Interneurons/metabolism* ; Neurodevelopmental Disorders/genetics* ; Neurons/metabolism* ; Rho Guanine Nucleotide Exchange Factors/genetics*