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Distal Hereditary Motor Neuropathy

dSMA


Presentation

  • Abstract Patients presenting with distal weakness can be a diagnostic challenge; the eventual diagnosis often depends upon accurate clinical phenotyping.[ncbi.nlm.nih.gov]
Italian
  • By a combination of autozygosity mapping, identity-by-descent segment detection and whole-exome sequencing approaches, we identified two novel homozygous mutations in the SIGMAR1 gene (p.E138Q and p.E150K) in two distinct Italian families affected by[ncbi.nlm.nih.gov]
Muscle Rigidity
  • Neurological examination showed an asymmetric tetraparesis, with muscle atrophy, predominantly in the lower limbs, associated to profound global arreflexia, bradykinesia, muscle rigidity, with cogwheeling, rest tremor (right hand), postural instability[deepdyve.com]
Hand Muscle Weakness
  • One family member demonstrated vocal cord palsy as the initial sign of disease; however, in the other family hand muscle weakness was the first major symptom. No affected patients demonstrated sensory loss or upper motor neuron involvements.[ncbi.nlm.nih.gov]
  • In affected FC465 members, respiratory difficulty during exercise was the initial and predominant symptom; however, in affected FC654 members, hand muscle weakness was the first dominant symptom.[spandidos-publications.com]
Small Hand
  • Physical examination revealed atrophy and weakness of small hand muscles and mild atrophy and weakness of the lower limbs. There was generalized hyperreflexia with the exception of ankle reflexes which were diminished.[ncbi.nlm.nih.gov]
Impulsivity
  • Maintaining proper axon diameter is essential for the efficient transmission of nerve impulses. The function of heat shock protein beta-8 is not well understood, but studies have shown that it interacts with heat shock protein beta-1.[ghr.nlm.nih.gov]
Pyramidal Tract Signs
  • Sensory abnormalities and pyramidal tract signs were absent in all cases, as was pes cavus. In all family members, the disease pursued a slowly progressive course that caused disability of proximal thigh muscles after 20 years of evolution.[nature.com]
Hyperreflexia
  • There was generalized hyperreflexia with the exception of ankle reflexes which were diminished. Her 25year-old son had only stiffness of both legs at the age of 22. Physical examination revealed only generalized hyporeflexia.[ncbi.nlm.nih.gov]
Akinesia
  • […] targeted analysis of a familial mutation TRPV4 - hereditary motor and sensory neuropathy type 2C This test is available for the following conditions: Conditions Neurological Motor neuropathy This product is also part of the following panels: WES fetal akinesia[order.radboudumc.nl]
Bradykinesia
  • Results : 45 years-old male patient presented progressive gait disorder, with lower limb weakness, associated to bradykinesia, followed by gait ataxia and falls since age 30 y.o.[deepdyve.com]
Postural Instability
  • Neurological examination showed an asymmetric tetraparesis, with muscle atrophy, predominantly in the lower limbs, associated to profound global arreflexia, bradykinesia, muscle rigidity, with cogwheeling, rest tremor (right hand), postural instability[deepdyve.com]

Treatment

  • The proteasomal inhibitor treatment increased the intracellular amount of σ1R(31_50del) and led to the formation of nuclear aggregates. Stable expressing σ1R(31_50del) induced endoplasmic reticulum stress and enhanced apoptosis.[ncbi.nlm.nih.gov]
  • Treatment varies based on a case-by-case basis. If you or a family member has been diagnosed with Jerash type distal hereditary motor neuropathy, talk with your doctor about the most current treatment options.[diseaseinfosearch.org]
  • The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.[orpha.net]
  • Physical therapy is the predominant treatment of symptoms.[ipfs.io]
  • Treatment with: -plasma exchange within 2 months of randomization.[clinicaltrials.jp]

Prognosis

  • Consequently, the correct diagnosis is important both for prognosis and for its value in genetic counseling.[clinicalgate.com]
  • Prognosis If patients with HSN I receive appropriate counselling and treatment, the prognosis is good. Early treatment of foot infections may avoid serious complications. Also the complications are manageable, allowing an acceptable quality of life.[ojrd.biomedcentral.com]
  • A specific genetic diagnosis can provide patients and their relatives with information about prognosis and recurrence risk and may be relevant to future gene-specific therapies ( 17, 22 ).[tidsskriftet.no]

Etiology

  • ., demyelinating vs. axonal), by etiology, or by pattern of inheritance. Spastic Paraplegia, Hereditary A group of inherited diseases that share similar phenotypes but are genetically diverse.[bioportfolio.com]
  • 結節性硬化症 Tuberous sclerosis complex (TSC), unknown genetic etiology 結節性硬化症、遺伝子型不明 1 不要 有 HPS2395 HPS2396 HPS2397 HPS2398 HPS2399 HPS2400 159.[cell.brc.riken.jp]
  • Several demyelinating etiologies can produce a “Dejerine-Sottas” phenotype with early onset, palpable nerves, and marked onion-bulb formation.[now.aapmr.org]
  • Although dHMN shows similar involvement of posterior compartment muscles, it also severely affects anterior compartment muscles, especially the vastus muscle group, which suggests that the etiologies and pathophysiologies of CMT1A and dHMN differ.[nature.com]
  • The etiology of PPS is not completely known, but it is most likely related to the normal aging process (i.e., most individuals lose some motor neurons after age 55 years) superimposed on chronically denervated muscles.[clinicalgate.com]

Epidemiology

  • CONCLUSION: Since next-generation sequencing will not be easily accessible, epidemiological data and clinical "phenotyping" remain the best strategy for clinicians to reach a correct genetic diagnosis in CMT2 and dHMN patients.[ncbi.nlm.nih.gov]
  • CONCLUSION Since next-generation sequencing will not be easily accessible, epidemiological data and clinical "phenotyping" remain the best strategy for clinicians to reach a correct genetic diagnosis in CMT2 and dHMN patients.[unboundmedicine.com]
  • Epidemiologic Study of Charcot-Marie-Tooth Disease: A Systematic Review. Neuroepidemiology. 2016. 46 (3):157-65. [Medline]. Garcia CA, Malamut RE, England JD, Parry GS, Liu P, Lupski JR.[emedicine.medscape.com]
  • Epidemiology Hereditary sensory neuropathy type I (HSN I) constitutes a clinically and genetically heterogenous group of disorders of low prevalence. No detailed epidemiological data are currently available.[ojrd.biomedcentral.com]
  • Epidemiology including risk factors and primary prevention HMSN is the most common inherited neuromuscular disease with overall prevalence of approximately 1/2500 and incidence 15/100,000 in the general population.[now.aapmr.org]
Sex distribution
Age distribution

Pathophysiology

  • Although dHMN shows similar involvement of posterior compartment muscles, it also severely affects anterior compartment muscles, especially the vastus muscle group, which suggests that the etiologies and pathophysiologies of CMT1A and dHMN differ.[nature.com]
  • Pathophysiology CMT1A The extra PMP22 gene copy within the 1.5 mB duplication on chromosome 17 is believed to cause most cases. [12] PMP22 is a 160 amino acid integral membrane protein that is expressed at high levels in myelinating Schwann cells, localizing[emedicine.medscape.com]

Prevention

  • Indeed, in vitro, both mutations reduce cell viability, the formation of abnormal protein aggregates preventing the correct targeting of sigma-1R protein to the mitochondria-associated ER membrane (MAM) and thus impinging on the global Ca 2 signalling[ncbi.nlm.nih.gov]
  • The NCARDRS helps scientists look for better ways to prevent and treat CMT. You can opt out of the register at any time. Page last reviewed: 18/02/2019 Next review due: 18/02/2022[nhs.uk]
  • Primary prevention is genetic counseling.[now.aapmr.org]
  • Heat shock protein 27 interacts with vimentin and prevents insolubilization of vimentin subunits induced by cadmium. Exp Mol Med 2005 ; 37 : 427 - 435 May DA, Disler DG, Jones EA, Balkissoon AA, Manaster BJ.[nature.com]
  • Genetic counselling is an important tool for preventing new cases if this is wished by at-risk family members.[ojrd.biomedcentral.com]

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