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The mechanochemical coupling of ATPase hydrolysis and conformational dynamics in kinesin motors facilitates intramolecular interaction cycles between the kinesin motor and neck domains, which are essential for microtubule-based motility. Here, we characterized a charge-inverting KIF1A-E239K mutant that we identified in a family with axonal-type Charcot-Marie-Tooth disease and also in 24 cases in human neuropathies including spastic paraplegia and hereditary sensory and autonomic neuropathy. We show that Glu239 in the ß7 strand is a key residue of the motor domain that regulates the motor-neck interaction. Expression of the KIF1A-E239K mutation has decreased ability to complement Kif1a+/- neurons, and significantly decreases ATPase activity and microtubule gliding velocity. X-ray crystallography shows that this mutation causes an excess positive charge on ß7, which may electrostatically interact with a negative charge on the neck. Quantitative mass spectrometric analysis supports that the mutation hyper-stabilizes the motor-neck interaction at the late ATP hydrolysis stage. Thus, the negative charge of Glu239 dynamically regulates the kinesin motor-neck interaction, promoting release of the neck from the motor domain upon ATP hydrolysis.
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Adenosina Trifosfatasas/genética , Cinesinas/genética , Mutación/genética , Neuronas/fisiología , Anciano , Secuencia de Aminoácidos , Axones/fisiología , Enfermedad de Charcot-Marie-Tooth , Humanos , Masculino , Microtúbulos/genética , Persona de Mediana Edad , Alineación de SecuenciaRESUMEN
INTRODUCTION: This study analyzes and describes atypical presentations of Charcot-Marie-Tooth disease type 4C (CMT4C). METHODS: We present clinical and physiologic features of 5 patients with CMT4C caused by biallelic private mutations of SH3TC2. RESULTS: All patients manifested scoliosis, and nerve conduction study indicated results in the demyelinating range. All patients exhibited signs of motor impairment within the first years of life. We describe 2 or more different genetic diseases in the same patient, atypical presentations of CMT, and 3 new mutations in CMT4C patients. DISCUSSION: A new era of unbiased genetic testing has led to this small case series of individuals with CMT4C and highlights the recognition of different genetic diseases in CMT4C patients for accurate diagnosis, genetic risk identification, and therapeutic intervention. The phenotype of CMT4C, in addition, appears to be enriched by a number of features unusual for the broad CMT category. Muscle Nerve 57: 749-755, 2018.
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Enfermedad de Charcot-Marie-Tooth , Mutación/genética , Proteínas/genética , Adolescente , Adulto , Animales , Animales Recién Nacidos , Enfermedad de Charcot-Marie-Tooth/complicaciones , Enfermedad de Charcot-Marie-Tooth/diagnóstico , Enfermedad de Charcot-Marie-Tooth/genética , Niño , Enfermedades Desmielinizantes/etiología , Femenino , Pruebas Genéticas , Humanos , Péptidos y Proteínas de Señalización Intracelular , Masculino , Ratas , Ratas Sprague-Dawley , Nervio Ciático/metabolismo , Escoliosis/etiologíaRESUMEN
OBJECTIVES: To analyse and describe the clinical and genetic spectrum of Charcot-Marie-Tooth disease (CMT) caused by mutations in the neurofilament light polypeptide gene (NEFL). METHODS: Combined analysis of newly identified patients with NEFL-related CMT and all previously reported cases from the literature. RESULTS: Five new unrelated patients with CMT carrying the NEFL mutations P8R and N98S and the novel variant L311P were identified. Combined data from these cases and 62 kindreds from the literature revealed four common mutations (P8R, P22S, N98S and E396K) and three mutational hotspots accounting for 37 (55%) and 50 (75%) kindreds, respectively. Eight patients had de novo mutations. Loss of large-myelinated fibres was a uniform feature in a total of 21 sural nerve biopsies and 'onion bulb' formations and/or thin myelin sheaths were observed in 14 (67%) of them. The neurophysiological phenotype was broad but most patients with E90K and N98S had upper limb motor conduction velocities <38 m/s. Age of onset was ≤3 years in 25 cases. Pyramidal tract signs were described in 13 patients and 7 patients were initially diagnosed with or tested for inherited ataxia. Patients with E90K and N98S frequently presented before age 3 years and developed hearing loss or other neurological features including ataxia and/or cerebellar atrophy on brain MRI. CONCLUSIONS: NEFL-related CMT is clinically and genetically heterogeneous. Based on this study, however, we propose mutational hotspots and relevant clinical-genetic associations that may be helpful in the evaluation of NEFL sequence variants and the differential diagnosis with other forms of CMT.
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Enfermedad de Charcot-Marie-Tooth/genética , Enfermedad de Charcot-Marie-Tooth/patología , Mutación/genética , Proteínas de Neurofilamentos/genética , Axones/patología , Ataxia Cerebelosa/genética , Ataxia Cerebelosa/patología , Genotipo , Humanos , Linaje , Fenotipo , Nervio Sural/patologíaRESUMEN
INTRODUCTION: Charcot-Marie-Tooth disease type 1C (CMT1C) is a rare, dominantly inherited neuropathy caused by mutations in the lipopolysaccharide-induced tumor necrosis factor (LITAF) or small integral membrane protein of the lysosome/late endosome (SIMPLE) gene. METHODS: We present a case series comprised of 10 patients in whom CMT1C is caused by a Gly112Ser substitution in the encoded protein. We focus on clinical presentation, electrodiagnostic analyses, and our findings in the context of previously described cases. RESULTS: The Gly112Ser mutation causing CMT1C is a mild form of CMT, as patients walked on time, had less weakness than those with Charcot-Marie-Tooth disease type 1A (CMT1A), had a CMT neuropathy score (CMTNS) indicative of mild disease, and had faster ulnar and median motor nerve conduction velocities compared to those with CMT1A. DISCUSSION: The G112S mutation in LITAF seems to be clinically indistinguishable from a mild presentation of CMT1A. Muscle Nerve 56: 1092-1095, 2017.
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Enfermedad de Charcot-Marie-Tooth/genética , Enfermedad de Charcot-Marie-Tooth/fisiopatología , Glicina/genética , Mutación/genética , Proteínas Nucleares/genética , Serina/genética , Factores de Transcripción/genética , Adolescente , Adulto , Anciano , Enfermedad de Charcot-Marie-Tooth/diagnóstico , Niño , Preescolar , Fenómenos Electrofisiológicos/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Inherited peripheral neuropathies, like many other degenerative disorders, have been challenging to treat. At this point, there is little specific therapy for the inherited neuropathies other than genetic counseling as well as symptomatic treatment and rehabilitation. In the past, ascorbic acid, progesterone antagonists, and subcutaneous neurotrophin-3 (NT3) injections have demonstrated improvement in animal models of CMT 1A, the most common inherited neuropathy, but have failed to translate any effect in humans. Given the difficulty in treatment, it is important to understand the molecular pathogenesis of hereditary neuropathies in order to strategize potential future therapies. The hereditary neuropathies are in an era of molecular insight and over the past 20 years, more than 78 subtypes of Charcot Marie Tooth disease (CMT) have been identified and extensively studied to understand the biological pathways in greater detail. Next generation molecular sequencing has also improved the diagnosis as well as the understanding of CMT. A greater understanding of the molecular pathways will help pave the way to future therapeutics of CMT. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
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Enfermedad de Charcot-Marie-Tooth , Neuropatías Hereditarias Sensoriales y Autónomas , Enfermedad de la Neurona Motora , Animales , Enfermedad de Charcot-Marie-Tooth/diagnóstico , Enfermedad de Charcot-Marie-Tooth/genética , Enfermedad de Charcot-Marie-Tooth/metabolismo , Enfermedad de Charcot-Marie-Tooth/patología , Enfermedad de Charcot-Marie-Tooth/terapia , Modelos Animales de Enfermedad , Neuropatías Hereditarias Sensoriales y Autónomas/diagnóstico , Neuropatías Hereditarias Sensoriales y Autónomas/genética , Neuropatías Hereditarias Sensoriales y Autónomas/metabolismo , Neuropatías Hereditarias Sensoriales y Autónomas/patología , Neuropatías Hereditarias Sensoriales y Autónomas/terapia , Humanos , Enfermedad de la Neurona Motora/diagnóstico , Enfermedad de la Neurona Motora/genética , Enfermedad de la Neurona Motora/metabolismo , Enfermedad de la Neurona Motora/patología , Enfermedad de la Neurona Motora/terapia , Neurotrofina 3/genética , Neurotrofina 3/metabolismoRESUMEN
INTRODUCTION: Symptoms and signs in women with Charcot-Marie-Tooth disease type 1X (CMT1X) are often milder from those in men, but the available electrophysiologic evidence regarding CMT1X in women has been characterized in some patients as non-uniform or asymmetric. METHODS: We retrospectively reviewed electrodiagnostic findings from 45 women and 31 men with CMT1X. RESULTS: Motor nerve conduction parameters in CMT1X women were less abnormal (P < 0.05), and a wider range of motor conduction velocities (CVs) were seen in women (P < 0.001) compared with men. In women, nerve conduction studies showed lack of conduction block without temporal dispersion. Motor CVs were more frequently in the normal range in women compared with men. There was no significant relationship to age of presentation and motor CV or compound muscle action potential in women. CONCLUSION: NCS parameters in CMT1X women did not demonstrate features suggestive of an acquired demyelinating neuropathy. Muscle Nerve, 2016 Muscle Nerve 54: -, 2016 Muscle Nerve 54: 728-732, 2016.
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Enfermedad de Charcot-Marie-Tooth/diagnóstico , Enfermedad de Charcot-Marie-Tooth/fisiopatología , Electrodiagnóstico/métodos , Conducción Nerviosa/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores Sexuales , Adulto JovenRESUMEN
INTRODUCTION: HINT1 mutations cause an autosomal recessive distal hereditary motor axonal neuropathy with neuromyotonia. This is a case report of a HINT1 mutation in the United States. METHODS: A 30-year-old man of Slovenian heritage and no significant family history presented with scoliosis as a child and later developed neuromyotonia and distal weakness. Electrodiagnostic testing revealed an axonal motor neuropathy and neuromyotonic discharges. Previous diagnostic work-up, including testing for Cx32, MPZ, PMP-22, NF-L, EGR2, CLCN1, DM1, DM2, SMN exon 7/8, emerin, LMNA, MPK, SCNA4, acid maltase gene, paraneoplastic disorder, and a sural nerve biopsy, was negative. RESULTS: Genetic testing for a HINT1 mutation was performed and revealed a homozygous mutation at p.Arg37Pro. CONCLUSION: This entity should be distinguished clinically and genetically from myotonic dystrophy and channelopathies with the clinical features of neuromyotonia and an axonal neuropathy. This case illustrates the importance of identifying the correct phenotype to avoid unnecessary and costly evaluations.
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Neuropatía Hereditaria Motora y Sensorial/genética , Síndrome de Isaacs/genética , Mutación/genética , Proteínas del Tejido Nervioso/genética , Adulto , Electrodiagnóstico , Neuropatía Hereditaria Motora y Sensorial/complicaciones , Humanos , Síndrome de Isaacs/complicaciones , Masculino , Estados UnidosRESUMEN
INTRODUCTION: We describe a 6-year-old girl with a T118M PMP22 mutation and heterozygous deletion of PMP22 on chromosome 17 (17p11.2-p12) resulting in a severe sensorimotor polyneuropathy. METHODS: This study is a case report in which the relevant mutations are described. RESULTS: Foot pain, cavovarus feet, tibialis anterior atrophy, absent reflexes, and inability to walk were found when the patient was age 6 years. Nerve conduction studies showed evidence of a sensorimotor polyneuropathy and compressive mononeuropathies of bilateral median nerves at the wrist and ulnar nerves at the elbow. Genetic testing revealed deletion of a PMP22 allele and T118M PMP22 mutation in the remaining allele. CONCLUSIONS: The severe sensorimotor polyneuropathy and hereditary neuropathy with liability to pressure palsies (HNPP) in this patient was likely a consequence of both decreased expression of PMP22 causing features consistent with HNPP and unopposed expression of the T118M mutant form of PMP22 that is relatively benign in the heterozygous state. The T118M mutant form of PMP22 can be disease-modifying in the appropriate circumstances.
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Mutación Missense/genética , Proteínas de la Mielina/genética , Polineuropatías/diagnóstico , Polineuropatías/genética , Síndrome de Smith-Magenis/genética , Niño , Deleción Cromosómica , Cromosomas Humanos Par 17/genética , Femenino , Humanos , Linaje , Polineuropatías/cirugíaRESUMEN
OBJECTIVES: Periodic paralysis is a rare genetic condition characterized by episodes of neuromuscular weakness, often provoked by electrolyte abnormalities, physiologic stress, physical exertion, and diet. In addition to mutations in genes coding for skeletal muscle ion channels, in 2019, Gustavasson et al discovered that the MCM3AP gene could be responsible for periodic paralysis. In this study, we present 2 individuals with clinical episodes of periodic paralysis who have variants in the MCM3AP gene. METHODS: Two unrelated probands were independently evaluated with clinical, genetic, and electrodiagnostic testing. RESULTS: Proband 1 is a 46-year-old man who presented with decades of ongoing episodic weakness and fatigue, clinically diagnosed with periodic paralysis and supported by electrodiagnostic studies. Proband 2 is a 34-year-old woman with a history of episodic paralysis since childhood. Genetic testing in both individuals revealed potentially pathogenic variants in the MCM3AP gene. CONCLUSIONS: Periodic paralysis is a condition that significantly affects the lives of those diagnosed. The results illustrate that MCM3AP gene variants can been associated with a clinical and electrodiagnostic presentation of periodic paralysis. Additional future research should focus on clarifying any relationship between these genetic variants and the disease, as well as other possible genetic causes.
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Distrofias Musculares , Masculino , Femenino , Humanos , Niño , Adulto , Persona de Mediana Edad , Músculo Esquelético , Fatiga , Pruebas Genéticas , Parálisis , Acetiltransferasas , Péptidos y Proteínas de Señalización IntracelularRESUMEN
This study presents the clinical and electrophysiological findings of four subjects with a pathogenic heterozygous GDAP1 variant causing Charcot-Marie-Tooth disease 2K (CMT2K) and one additional subject with an uncertain GDAP1 variant and clinical findings of CMT 2K. The study evaluated these five subjects using clinical, laboratory, electrophysiological, and genetic testing. The findings showed that clinical features demonstrated no pes cavus, no significant weakness in the hands or feet, normal reflexes in four out of the five subjects, and mild to normal electrodiagnostic findings. The variant was associated with painful and numb feet with diminished sensation to pinprick. This study suggests that GDAP1 variants may be associated with very mild, predominantly sensory Charcot-Marie-Tooth disease, warranting continuing research for this type of the disease.
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Valosin containing protein (VCP) mutations have been reported to present with a high degree of variability and can be present in patients even if they may have an initial normal work up. A 55-year-old woman was labeled as "normal" and "pain medication seeking" after an unrevealing work up of clinical, laboratory, electrodiagnostic, radiographic, pathologic, and genetic testing. She continued to present with chronic neck pain, and had variable features of scapuloperoneal atrophy, which was also seen in her family. The patient and her family were found to have a known pathogenic c.464G>A, p.Arg155His (R155H) mutation in the VCP gene. Despite traditional thinking of attempting to localize neurological syndromes, VCP mutations are difficult to localize as they can present with significant clinical heterogeneity including a scapuloperoneal syndrome with variable neuropathic and myopathic features.
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Mutations in MFN2 cause a range of Charcot-Marie-Tooth disease (CMT) phenotypes with different inheritance patterns and underlying pathogenic mechanisms. Recently, a family with a dominantly inherited CMT harboring c.2222T>G (p.Leu741Trp) mutation in MFN2 has been reported for the first time. Here, we report a second family also with a dominantly inherited CMT harboring the same mutation, thereby confirming the pathogenicity of this mutation. Interestingly, the disease onset of this second family is much later than the previously reported cases.
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Enfermedad de Charcot-Marie-Tooth/genética , GTP Fosfohidrolasas/genética , Proteínas Mitocondriales/genética , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , LinajeRESUMEN
TITLE: Survey of the functional priorities in patients with disability due to neuromuscular disorders. OBJECTIVE: This study attempts to determine the functional priorities for patients with neuromuscular disorders. METHODS: A survey asking about functional priorities with respect to activities of daily living, ankle foot orthotic design, and assistive device design, was distributed to patients with neuromuscular disorders to assess the needs of patients from their perspectives. Descriptive statistics were used to analyse answers. RESULTS: A total of 171 subjects with neuromuscular disorders responded to the questionnaire. Of the respondents with weakness in both the upper and lower extremities, 45% stated that if they had to choose between correction of one or the other, they would prefer that of their lower extremities. Activities that patients most frequently wanted to gain independence with were mobility and transfers (46%), followed by toilet use and hygiene (32%). The most popular control mechanism of an assistive device was voice activation (35%). CONCLUSION: This study assessed the functional priorities of those with neuromuscular disorders. Although such individuals can experience a range of weakness in the upper and/or lower extremities, common functional priorities were reported: independence with mobility, transfers, toilet use and hygiene. Knowledge of these priorities will help guide development of assistive devices that will restore function in the future. Implications for Rehabilitation Neuromuscular Disorders ⢠Neuromuscular disorders result in disabling weakness; there are few cures and many are unable to carry out activities of daily living. ⢠Information that would be helpful in determining functional priorities is limited. ⢠In a survey of 171 patients with neuromuscular disorders, functional priorities included mobility and transfers (46%), followed by toilet use and hygiene (32%). ⢠Of the respondents with weakness in both the upper and lower extremities, 45% stated that if they had to choose between correction of one or the other, they would prefer that of their lower extremities. ⢠If an assistive device were to be created to help those with neuromuscular disorders, the most popular control mechanism would be voice activation (35%).
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Actividades Cotidianas , Personas con Discapacidad , Extremidad Inferior/fisiopatología , Evaluación de Necesidades , Enfermedades Neuromusculares/fisiopatología , Aparatos Ortopédicos , Dispositivos de Autoayuda , Adolescente , Adulto , Anciano , Niño , Preescolar , Diseño de Equipo , Femenino , Humanos , Iowa , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
Hereditary sensory and autonomic neuropathy type I (HSAN I) is an autosomal dominant disease characterized by distal sensory loss, pain insensitivity, and autonomic disturbances. The major underlying causes of HSAN I are point mutations in the SPTLC1 gene. Patients with mutations in the SPTLC1 genes typically exhibit dense sensory loss and incidence of lancinating pain. Although most of these mutations produce sensory loss, it is unclear which mutations would lead to the painful phenotype. In this case series, we report that the V144D mutation in SPTLC1 gene may relate to both painful and painless peripheral neuropathies. The unique clinical phenotype of this mutation may guide clinical workup and treatment for patients with painful and painless neuropathies.
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The clinical effect of T118M variant of the PMP22 gene has been controversial. Several studies have suggested that it may be autosomal recessive, partial loss of function, or a benign variant. Here we report three cases in further support that the T118M variant of the PMP22 gene is a partial loss of function variant. These three unrelated cases were heterozygotes with the T118M variant of the PMP22 gene. All three cases presented with painful peripheral neuropathy and varying degrees of Charcot-Marie-Tooth exam features. Electrophysiological studies revealed polyneuropathy with axonal and demyelinating features in one case, but there were minimal electrophysiological changes in the other two cases. We propose that the T118M variant can cause painful peripheral neuropathy, which may be an underrecognized feature of this variant.
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INTRODUCTION: Mutations in the gene encoding DNA polymerase gamma (POLG) impair its ability to proofread mitochondrial DNA (mtDNA) during replication [1]. This results in a high frequency of randomly distributed mtDNA mutations and thus a wide range of phenotypes, including seizures, neuropathy, and cerebellar ataxia [1, 2]. We document a phenotype associated with the rare POLG variant c.1370G>A (p.R457Q). METHODS: Over 10 years, we performed electrodiagnostic and neuropsychologic on a patient who presented with a variety of neurologic symptoms. RESULTS: Testing revealed an axonal sensorimotor polyneuropathy, depression and executive function difficulties, and asymmetric ataxia. Genetic testing revealed a POLG variant of uncertain significance (c.1370G>A, p.R457Q) in a heterozygous state. CONCLUSIONS: We have identified a mutation in POLG that could result in a diverse array of symptoms and signs of our patient. However, interpreting pathogenicity of rare variants such as R457Q is challenging and will likely require identification of patients with similar phenotypes caused by the variant of uncertain significance.
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Ataxia/genética , ADN Polimerasa gamma/genética , Depresión/genética , Epilepsia/genética , Trastornos de la Memoria/genética , Polineuropatías/genética , Anciano , Ataxia/fisiopatología , Depresión/fisiopatología , Progresión de la Enfermedad , Electromiografía , Epilepsia/fisiopatología , Función Ejecutiva , Variación Genética , Heterocigoto , Humanos , Masculino , Trastornos de la Memoria/fisiopatología , Conducción Nerviosa , Polineuropatías/fisiopatologíaRESUMEN
PURPOSE: Charcot-Marie-Tooth Disease type 1A (CMT1A) is caused by a duplication of the peripheral myelin protein gene 22 at chromosome 17p11.2-12. There is limited data regarding whether body mass index (BMI) affects electrophysiological or clinical data in those with CMT1A. METHODS: Electrophysiological data, the Charcot-Marie-Tooth examination score (CMTES) and BMI from 101 patients with known CMT1A were obtained and analyzed. RESULTS: When controlling for age, a higher BMI does not affect ulnar motor nerve conduction studies in those with CMT1A, but rather components of the CMTES (loss of pinprick and motor strength in the lower extremities). CONCLUSIONS: BMI and clinical components of the CMTES are correlated, but it is uncertain which came first-whether the loss of lower extremity pinprick sensation and motor strength results in a higher BMI or if higher BMI results in these signs.
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Índice de Masa Corporal , Enfermedad de Charcot-Marie-Tooth/fisiopatología , Conducción Nerviosa/fisiología , Adulto , Enfermedad de Charcot-Marie-Tooth/complicaciones , Electrodiagnóstico , Femenino , Humanos , Extremidad Inferior/fisiopatología , Masculino , Persona de Mediana Edad , Fuerza Muscular/fisiología , Obesidad/complicaciones , Obesidad/fisiopatología , Análisis de Regresión , Sensación/fisiología , Trastornos Somatosensoriales/complicaciones , Trastornos Somatosensoriales/fisiopatología , Nervio Cubital/fisiopatologíaRESUMEN
We present a report of a 47-year-old woman with developmental delay who presented with subarachnoid hemorrhage and acute hydrocephalus. She did not have an aneurysm, but there was symmetric calcification and gadolinium-enhancement of the meninges within the Sylvian fissure. Biopsy and genetic testing confirmed transthyretin-type amyloidosis. It is important to consider such rare causes in atypical presentations of non-aneurysmal subarachnoid hemorrhage.
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Neuropatías Amiloides Familiares/complicaciones , Hidrocefalia/etiología , Hemorragia Subaracnoidea/etiología , Femenino , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: We report a unique finding of a patient whose restless legs syndrome (RLS) symptoms abated after the placement of a spinal cord stimulator for chronic neuropathic pain. RLS is a common disorder, with many patients unable to find sufficient relief from their symptoms. CASE DESCRIPTION: A patient diagnosed with neuropathic pain who also suffered from RLS symptoms despite medication therapy underwent implantation of a spinal cord stimulator after a successful trial. This patient was interviewed formally about his RLS symptoms immediately before his procedure and at 6 weeks, 6 months, and 2.5 years after the procedure. The patient also completed the International Restless Legs Syndrome Scale questionnaire to objectively quantify the severity of his symptoms. Finally, the patient kept a 5-day journal detailing when the stimulator was in use. The patient reported subjective symptomatic improvement in his RLS symptoms with improved sleep quality and quantity, in addition to improvement in his back pain. The patient's score on the International Restless Legs Syndrome Scale improved after implantation from 33 to 0 on a 40-point scale. Moreover, when asked to keep a journal record of his stimulator use, the patient noted that he only used the stimulator before going to bed to help his RLS symptoms and no longer required any medication for his previous RLS symptoms. CONCLUSIONS: Epidural stimulation may be an additional, alternative, or novel therapy in the treatment of RLS.
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Espacio Epidural/fisiología , Síndrome de las Piernas Inquietas/terapia , Estimulación de la Médula Espinal , Anciano , Espacio Epidural/diagnóstico por imagen , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Síndrome de las Piernas Inquietas/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Introduction. Hereditary Spastic Paraplegia (HSP) is a rare hereditary disorder that primarily involves progressive spasticity of the legs (hamstrings, quadriceps, and calves). Methods. A 27-year-old gentleman was a fast runner and able to play soccer until age 9 when he developed slowly progressive weakness. He was wheelchair-bound by age 25. He was evaluated by laboratory testing, imaging, electrodiagnostics, and molecular genetics. Results. Electrodiagnostic testing revealed an axonal sensorimotor polyneuropathy. Genetic testing for HSP in 2003 was negative; repeat testing in 2013 revealed a mutation in KIF5A (c.611G>A;p.Arg204Gln). Conclusions. A recent advance in neurogenetics has allowed for more genes and mutations to be identified; over 76 different genetic loci for HSP and 59 gene products are currently known. Even though our patient had a sensorimotor polyneuropathy on electrodiagnostic testing and a 2003 HSP genetic panel that was negative, a repeat HSP genetic panel was performed in 2013 due to the advancement in neurogenetics. This revealed a mutation in KIF5A.