scholarly journals Phenoconversion from Spastic Paraplegia to ALS/FTD Associated with CYP7B1 Compound Heterozygous Mutations

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1876
Author(s):  
Julian Theuriet ◽  
Antoine Pegat ◽  
Pascal Leblanc ◽  
Sandra Vukusic ◽  
Cécile Cazeneuve ◽  
...  
Keyword(s):  
Lower Limb ◽  
Clinical Symptoms ◽  
Compound Heterozygous ◽  
Spastic Paraplegia ◽  
The Third ◽  
Limb Spasticity ◽  
Lower Limb Spasticity ◽  
Compound Heterozygous Mutations ◽  
Biallelic Mutations ◽  
Lateral Sclerosis

Biallelic mutations in the CYP7B1 gene lead to spastic paraplegia-5 (SPG5). We report herein the case of a patient whose clinical symptoms began with progressive lower limb spasticity during childhood, and who secondly developed amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) at the age of 67 years. Hereditary spastic paraplegia (HSP) gene analysis identified the compound heterozygous mutations c.825T>A (pTyr275*) and c.1193C>T (pPro398Leu) in CYP7B1 gene. No other pathogenic variant in frequent ALS/FTD causative genes was found. The CYP7B1 gene seems, therefore, to be the third gene associated with the phenoconversion from HSP to ALS, after the recently described UBQLN2 and ERLIN2 genes. We therefore expand the phenotype associated with CYP7B1 biallelic mutations and make an assumption about a link between cholesterol dyshomeostasis and ALS/FTD.

scholarly journals Case report on novel mutation in SPAST gene in Polish family with spastic paraplegia

BMC Neurology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Aleksandra Klimkowicz-Mrowiec ◽  
Anna Dziubek ◽  
Malgorzata Sado ◽  
Marek Karpiński ◽  
Agnieszka Gorzkowska
Keyword(s):  
Case Report ◽  
Genetic Testing ◽  
Family History ◽  
Lower Limb ◽  
Hereditary Spastic Paraplegia ◽  
Novel Mutation ◽  
Family Members ◽  
Spastic Paraplegia ◽  
Limb Spasticity ◽  
Lower Limb Spasticity

Abstract Background Hereditary spastic paraplegia is a large group of degenerative, neurological disorders characterized by progressive lower limb spasticity and weakness. The disease was investigated precisely but still clinicians often make incorrect or late diagnosis. Our aim was to investigate the genetic background and clinical phenotype of spastic paraplegia in large Polish family. Case presentation A 37 years old woman presented with 4-year history of walking difficulties. On neurological examination, she had signs of upper motor lesion in lower extremities. She denied sphincter dysfunction and her cognition was normal. Her family history was positive for individuals with gait problems. The initial diagnosis was familial spastic paraplegia. Genetic testing identified a novel mutation in SPAST gene. All available family members were examined and had genetic testing. The same mutation in SPAST gene was identified in other affected family members. All patients caring the mutation presented with different phenotypes. Conclusion This study presents a family with spastic paraplegia due to a novel mutation c.1390G›T(p.Glu464Term) in SPAST gene. Affected individuals showed a range of phenotypes that varied in their severity. This case report demonstrates, the signs of hereditary spastic paraplegia can be often misdiagnosed with other diseases. Therefore genetic testing should always be considered in patients with lower limb spasticity and positive family history in order to help to establish the correct diagnosis.

scholarly journals Novel Splice-Site and Missense Variant of PNPLA6 in an Austrian Family Causing Spastic Paraplegia-39 with Cerebellar Oculomotor Disorder

2022 ◽  
Author(s):  
Sebastian Viertauer ◽  
Ingo Kurth ◽  
Katja Eggermann ◽  
Christian Eggers
Keyword(s):  
Splice Site ◽  
Lower Limb ◽  
Clinical Symptoms ◽  
Hypogonadotropic Hypogonadism ◽  
Missense Variant ◽  
Compound Heterozygous ◽  
Spastic Paraplegia ◽  
Meaningful Improvement ◽  
Pathogenic Variants ◽  
Splice Site Variant

Abstract Background The term hereditary spastic paraplegia comprises an ever-expanding array of neurological disorders with distinct aetiologies. Spastic paraplegia 39 is one of the many variants with additional features of other organs and neurological systems. We describe a large kindred with two hitherto undescribed mutations of PNPLA6 and a novel clinical phenotype as, in addition to spastic paraplegia, affected subjects suffered from a prominent cerebellar oculomotor dysfunction. Methods Three of five genetically tested family members of a large kindred were affected by spastic gait and cerebellar oculomotor dysfunction. Clinical, imaging, laboratory and electrophysiological data were analyzed. Genetic analysis was done using next-generation sequencing. Segregation analyses were performed by Sanger sequencing. To assess the pathogenicity of genetic variants on the encoded protein, in silico assessments were carried out. Results Two hitherto unknown sequence variants in the PNPLA6 gene, a splice-site variant c.1635+3G>T and a missense variant c.3401A>T, p.(Asp1134Val), were detected. Compound-heterozygous siblings presented with lower limb spasticity and a marked cerebellar oculomotor disorder accompanied by moderate hypogonadotropic hypogonadism in the female. A paternal uncle being homozygous for the splice-site variant of PNPLA6 presented with increased lower limb reflexes, an unstable gait and cerebellar oculomotor dysfunction. Treatment with 4-aminopyridin, a potassium channel blocker, lead to meaningful improvement of clinical symptoms. Conclusion PNPLA6 gene variants are associated with a broad phenotypic spectrum to which we add cerebellar oculomotor dysfunction. In our kindred, the full clinical manifestation only occurred in compound-heterozygous subjects indicating that biallelic pathogenic variants lead to more serious and earlier onset of symptoms. Our findings emphasize the role of PNPLA6 in different neurodegenerative disorders.

Poster 75: Exploring Real-World OnabotulinumtoxinA Utilization Patterns for the Treatment of Lower Limb Spasticity: The Adult Spasticity International Registry (ASPIRE) Study

PM&R ◽  
2018 ◽  
Vol 10 ◽  
pp. S31-S31
Author(s):  
Alberto Esquenazi ◽  
Wolfgang H. Jost ◽  
Ganesh Bavikatte ◽  
Daniel S. Bandari ◽  
Michael C. Munin ◽  
...  
Keyword(s):  
Real World ◽  
Lower Limb ◽  
International Registry ◽  
Utilization Patterns ◽  
Limb Spasticity ◽  
Lower Limb Spasticity

scholarly journals The effectiveness of additional core stability exercises in improving dynamic sitting balance, standing balance, lower-limb spasticity, falls and gait in subacute stroke patients (CORE-trial). Study protocol for a Randomized Controlled Trial

2021 ◽  
Author(s):  
Rosa Cabanas-Valdés ◽  
Lidia Boix-Sala ◽  
Montserrat Grau-Pellicer ◽  
Juan Antonio Guzmán-Bernal ◽  
Fernanda Maria Caballero-Gómez ◽  
...  
Keyword(s):  
Lower Limb ◽  
Daily Living ◽  
Controlled Trial ◽  
Core Stability ◽  
Standing Balance ◽  
Stroke Patients ◽  
Randomized Controlled ◽  
Limb Spasticity ◽  
Lower Limb Spasticity ◽  
Dynamic Sitting

Abstract BackgroundTrunk impairment produces disorders of motor control, balance, and gait that are correlated with increased risk of falls and reduced mobility in stroke survivors. This creates disability and dependency to perform their activities of daily living. Alterations in body alignment occur, requiring treatment strategies focused on improving the postural control. bearing. Core stability exercises (CSE) are a good strategy to improve local strength of trunk, dynamic sitting, standing balance, and gait. There is some evidence about its effectiveness but it is still necessary to run a large multicenter trial to ratify that existing evidence.MethodsThis is a single-blind multicenter randomized controlled trial. Two parallel groups are compared and both perform the same type of therapy. A control group (CG) (n=110) performs conventional physiotherapy (CP) (1 hour per session) focused on improving balance. An experimental group (EG) (n=110) performs CSE (30 minutes) in addition to CP (30 minutes) (1 hour/session in total). EG is divided in two subgroups, in which only half of patients (n=55) perform CSE plus transcutaneous electrical nerve stimulation (TENS). Primary outcome measures are dynamic sitting, assessed by Spanish-version of Trunk Impairment Scale and stepping, assessed by Brunel Balance Assessment. Secondary outcomes are postural control, assessed by Postural Assessment Scale for Stroke patients; standing balance and risk of fall assessed by Berg Balance Scale; gait speed by BTS G-Walk (accelerometer); rate of falls, lower-limb spasticity by Modified Ashworth Scale; activities of daily living by Barthel Index; and quality of life by EQ-5D-5L. These are evaluated at baseline (T0), at 3 weeks (T1), at 5 weeks -at the end of the intervention (T2), at 17 weeks (T3) and at 29 weeks (T4). Study duration per patient is 29 weeks (a 5-week intervention, followed by a 24-week post-intervention). DiscussionThe study will provide useful information on the short and long term effects of a physiotherapy rehabilitation program based on core stability exercises performed in subacute phase.Trial registrationClinicalTrials.gov Identifier NCT03975985. Data registration June 5th, 2019. Retrospectively registered. Date of registration in primary registry: June 5, 2019. Protocol version 1

scholarly journals A STUDY OF RELATION OF LOWER LIMB SPASTICITY WITH LIPID PROFILE AND FASTING PLASMA GLUCOSE LEVELS IN CHRONIC MOTOR COMPLETE SPINAL CORD INJURY PATIENTS.

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Batra Amit ◽  
Prakash Om ◽  
Jindal Rajeshwari ◽  
Batra Shivra
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Lower Limb ◽  
Density Lipoprotein ◽  
Fasting Plasma ◽  
Cord Injury ◽  
Limb Spasticity ◽  
Lower Limb Spasticity

Background: Most common cause of spinal cord injury in India is fall from height followed by road accidents which may lead to incomplete or complete disruption of neural signal transmission across and below the level of injury. Spasticity is a common but not an inevitable complication following spinal cord injury. Study Objective: The present study tried to explore the correlation between the lower limb spasticity following spinal cord injury and the metabolic markers. Study design: Hospital-based cross-sectional study. Material and Methods: Fifty patients recruited from Department of Physical Medicine and Rehabilitation, Sawai Man Singh Hospital, Jaipur (Raj.), were categorized into mild (16),moderate (11), and severe (23)spastic groups based on assessment of  ankle/knee extensor muscle group spasticity using the modified Ashworth scale. The metabolic profile markers such as Total Cholesterol (TC), Low-density Lipoprotein (LDL), High-Density Lipoprotein (HDL), Triglyceride (TG) and Fasting Plasma Glucose (FPG) were estimated and compared between the three groups. Results: The triglycerides, total cholesterol, low density lipoproteins and the fasting plasma glucose level were significantly negatively correlated with the grading of spasticity in lowerlimbs (P <0.001). The high density lipoproteins level was higher in a severe spastic group as compared to the mild and moderate spastic groups; but this result was statistically non-significant (P=0.14). Conclusion: Spasticity in motor complete SCI may have beneficial effects in preserving glucose homeostasis and defending rise in adiposity, rationalizing the need for its judicious management to maintain the crucial balance between its beneficial and problematic effects. Keywords: Spasticity, Modified Ashworth score, Spinal cord injury, lipid profile, fasting plasma glucose.

Sign in / Sign up

Export Citation Format

Share Document