Edit concept Question Editor Create issue ticket

Autosomal Recessive Lower Motor Neuron Disease with Childhood Onset

Distal spinal muscular atrophy type 4


Presentation

  • His research focuses on understanding the variation in the clinical presentations of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) and finding biomarkers for them.[books.google.com]
  • Grasp and apply the latest knowledge from more than 25 brand-new chapters, as well as extensive revisions or total rewrites to the majority of existing chapters to present all of the most up-to-date information available on every aspect of spine surgery[books.google.com]
  • Usually @ C8-T1 - so in upper extremity mostly Presents Disrupt lateral spinothalamic tract bilaterally Loss of nociception Loss of temperature sense Intact tactile sensation, proprioception - as decussate in medulla dorsal column-medial lemniscus pathway[alancam.com]
  • Some people present with generalized weakness in infancy while others present with adult-onset weakness that may include proximal muscles and sensory loss. Many people’s first symptom is cramping in the legs.[cmtausa.org]
  • Fasciculations and cramps are present. Bulbar involvement is often mild and occurs late in the disease.[neuroweb.us]
Movement Disorder
  • Standardized criteria are also provided for epilepsy, genetic syndromes, headache, immune-based disorders, infectious diseases, movement disorders, neuromuscular disorders, and sleep disorders.[books.google.com]
  • Find the answers you need on the hottest topics in neurology, including involuntary movement disorders; single gene mutations with neuropsychiatric manifestations; psychiatric comorbidity of neurologic illnesses and treatments; deep brain stimulation[books.google.com]
  • disorders due to brain damage that are non-progressive and acquired in utero, during birth or after infancy -Etiology, can occur before or during birth secondary to lack of oxygen, maternal infections, drug or alcohol abuse, placental abnormalities,[quizlet.com]
Epilepsy
  • Standardized criteria are also provided for epilepsy, genetic syndromes, headache, immune-based disorders, infectious diseases, movement disorders, neuromuscular disorders, and sleep disorders.[books.google.com]
  • […] pediatric neurology evolved as an identified specialty as the volume and complexity of data became too much for the general pediatician or the adult neurologist to master, the discipline has now continued to evolve into so many subspecialties, such as epilepsy[books.google.com]
  • Hence clinical features include progressive cerebellar ataxia, or dementia with chorea, or prominent chorea and dystonia or progressive myoclonic epilepsy.[neuroweb.us]
Muscle Weakness
  • Four of the five affected patients had muscle weakness since age 3, strongly worsening during childhood and leading to generalized tetraplegia in adulthood.[ncbi.nlm.nih.gov]
  • Muscle weakness may be associated with soreness in the muscles and joint pain.[rarediseases.org]
  • Muscle weakness Loss of motor neurons in the spinal cord In MND causes muscle weakness.[4].The earliest symptom is usually asymmetrical weakness of one extremity or, with bulbar onset disease, slurring of speech.[5].[explainmedicine.com]
Myopathy
  • Options include the following: Myopathies: -Myopathy Expanded Panel (141 genes) -Muscular Dystrophy Panel (77 genes) -Congenital Myopathy Panel (36 genes) -Metabolic Myopathy Panel (41 genes) -Myofibrillar Myopathy Panel (12 genes) -Distal Myopathy Panel[mayomedicallaboratories.com]
  • LGMD2B is caused by mutations of a gene that also causes Miyoshi myopathy a rare muscle disorder characterized by weakness of the distal muscles of the legs and arms.[rarediseases.org]
  • SMA1 must be distinguished from other causes of neonatal hypotonia which include CNS malformations, metabolic diseases, infections, and congenital myopathies.[neuropathology-web.org]
  • Differential diagnosis Motor neurone disease Primary lateral sclerosis Muscular dystrophy Congenital myopathies Disorders of carbohydrate metabolism ( glycogen storage diseases ) Myasthenia gravis Poliomyelitis Investigations Blood tests Creatine kinase[patient.info]
  • Polyglucosan body myopathy: a new case. Neuromuscul Disord. 1992; 2 :419–22. [ PubMed : 1300190 ] Traynor BJ, Codd MB, Corr B, Forde C, Frost E, Hardiman O. Incidence and prevalence of ALS in Ireland, 1995-1997: a population- based study.[ncbi.nlm.nih.gov]
Proximal Muscle Weakness
  • LGMD2L (anoctominopathy) Affected individuals were reported to have proximal muscle weakness in lower and upper limbs and muscle hypertrophy was common. Intelligence was reported to be normal.[rarediseases.org]
  • In 4 of the 5 patients having a severe phenotype, symptoms appeared during infancy (2 to 3.5 years), with proximal muscle weakness predominating in the lower limbs and early involvement of foot and hand muscles.[pediatricneurologybriefs.com]
  • muscle weakness and early involvements of foot and hand Muscle weakness Upper limb, proximal No Yes Upper limb, distal Yes Yes Lower limb, proximal Yes Yes Lower limb, distal Yes Yes Muscle atrophy Proximal distal Proximal distal (generalized) Sensory[ojrd.biomedcentral.com]
Lordosis
  • Additional abnormalities that may develop in individuals with LGMD include abnormal side-to-side curvature of the spine (scoliosis), abnormal front-to-back curvature of the spine (lordosis), thickening and shortening of tissue that cause deformity and[rarediseases.org]
  • […] mother is a silent carrier and only male offspring will manifest disease Duchenne Muscular Dystrophy -Symptoms manifest between 2 and 5 years Duchenne Muscular Dystrophy -Progressive weakness, disinterest in running, falling, toe walking, excessive lordosis[quizlet.com]
Back Pain
  • pain and psychosocial interactions, biomechanics, and more.[books.google.com]
  • Aseptic meningitis with headache, back pain, and stiff neck develop with increasing severity of the disease.[clinicalgate.com]
Behavior Disorder
  • ., brain tumors), including cerebrovascular diseases, dementias and behavioral disorders, demyelinating disorders, and disorders of consciousness and brain death.[books.google.com]
Areflexia
  • Paralysis spread to become generalized, except for the cranial nerves, and by age 16 years, patients were tetraplegic with areflexia, contractures, and scoliosis, and required assisted respiratory ventilation. Intelligence was preserved.[pediatricneurologybriefs.com]
  • Patients typically present during infancy or early childhood with progressive weakness, hypotonia , muscle atrophy , hyporeflexia/areflexia, and varying degrees of bulbar weakness.[amboss.com]
  • […] weakness and early involvements of foot and hand Muscle weakness Upper limb, proximal No Yes Upper limb, distal Yes Yes Lower limb, proximal Yes Yes Lower limb, distal Yes Yes Muscle atrophy Proximal distal Proximal distal (generalized) Sensory loss Yes No Areflexia[ojrd.biomedcentral.com]
  • The paralysis is usually asymmetrical, predominantly involving the proximal muscles (lower limbs) with pain and tenderness with typical weakness, flaccidity and areflexia. The extent is variable from one muscle group to complete tetraparesis.[neuroweb.us]
  • Joint contractures, severe progressive scoliosis, and restrictive lung disease were present in most of the SMA II individuals, but these complications were less frequently identified in SMA III. 32 Hand tremor, tongue fasciculations, and areflexia are[clinicalgate.com]
Paresis
  • As disease progresses, a hoarse voice can develop and vocal cord paresis have been reported. Life expectancy and intelligence are not affected.[cmtausa.org]
  • The mechanism of dysarthria is a flaccid or spastic paresis of the musculature of the face, tongue, lips, palate, pharynx and larynx. At the early stage of ALS patient may experience a mild change in his voice or speech.[explainmedicine.com]
  • .  Diagnosis of exclusion Account for 2-4% of ALS Absence of LMN Invovement Presentation in early 50’s Slowly evolving spastic paresis after involving upperlimbs. Median disease duration:19yrs Fasiculation,cramps,bladder dysfunction,cognitivedeficits[slideshare.net]
  • […] present -Autosomal recessive ataxia -Results from gene mutation causing abnormal repetition of DNA sequence and ultimately, impaired mitochondrial function -Gait unsteadiness begins early in life and is followed by upper extremity ataxia dysarthria, and paresis[quizlet.com]
Headache
  • Standardized criteria are also provided for epilepsy, genetic syndromes, headache, immune-based disorders, infectious diseases, movement disorders, neuromuscular disorders, and sleep disorders.[books.google.com]
  • Aseptic meningitis with headache, back pain, and stiff neck develop with increasing severity of the disease.[clinicalgate.com]
Involuntary Movements
  • Find the answers you need on the hottest topics in neurology, including involuntary movement disorders; single gene mutations with neuropsychiatric manifestations; psychiatric comorbidity of neurologic illnesses and treatments; deep brain stimulation[books.google.com]
Stroke
  • […] identified specialty as the volume and complexity of data became too much for the general pediatician or the adult neurologist to master, the discipline has now continued to evolve into so many subspecialties, such as epilepsy, neuromuscular disease, stroke[books.google.com]

Treatment

  • […] and other new treatments; and the neurologic effects of illicit drug use.[books.google.com]
  • Yet, immunoglobulin treatment is based on the assumption of inflammatory etiology of MMND, but not a proven treatment. Rarity of MNND in itself is an impediment for evolving a possible treatment.[rarediseasesindia.org]
  • Management There is currently no effective curative treatment. [ 11 ] There is no proven effective drug treatment for SMA. [ 12, 13 ] However, scientific and clinical advances are currently heading towards developing effective treatment(s) for people[patient.info]
  • […] of the FVC. Spportive treatment Spasticity(Baclofen/tizanidine), Cramps(Vit B complex,CCB,levitriacetam), Sialorrhoea(TCA,anticholinergics), Depression(SSRIs/TCA) Diaphragm pacing has been used in selected patientswith ALS with moderately impaired[slideshare.net]
  • Type I non-sitters , type II sitters, type III walkers References: [1] [4] Treatment Subtypes and variants Non-5q spinal muscular atrophy Definition : variants of SMA that are not associated with a defect in the SMN1 gene on chromosome 5q X-linked spinal[amboss.com]

Prognosis

  • The older the age of onset, the better the prognosis![amboss.com]
  • Complications Spinal deformity Joint contractures Respiratory infection Respiratory failure Prognosis Although SMA involves a wide range of disease severity and a high mortality and morbidity rate, recent advances in multidisciplinary supportive care[patient.info]
  • Deletions of NAIP gene were mainly seen in severely affected patients, hence is useful to predict prognosis. 1. Katirji B, Kaminski HJ, Preston DC, Ruff RL, Shapiro BE. Neuromuscular disorders in clinical practice.[annalsofian.org]
  • This variant is called progressive bulbar palsy and has a worse prognosis. Some ALS patients have only lower motor neuron involvement (progressive muscular atrophy). Frontotemporal dementia develops in a significant proportion of ALS patients.[neuropathology-web.org]

Etiology

  • […] disorder results in deterioration and irreversible damage within cerebral cortex and subcortical areas -Neurons normally involved with acetylcholine transmission deteriorate within the cerebral cortex -Amyloid plaques and neurofibrillary tangles -unknown etiology[quizlet.com]
  • Etiology Pathophysiology Clinical features The most common causes of death among patients with SMA are respiratory insufficiency (due to respiratory muscle weakness ) and aspiration pneumonia (due to bulbar weakness)![amboss.com]
  • TABLE 452-1 Etiology of Motor Neuron Disorders View Table Favorite Table Download (.pdf) TABLE 452-1 Etiology of Motor Neuron Disorders Diagnostic Category Investigation Structural lesions Parasagittal or foramen magnum tumors Cervical spondylosis Chiari[accessmedicine.mhmedical.com]
  • Inflammatory etiology in MMND is suggested.[rarediseasesindia.org]
  • Introduction to the disease Motor neuron disease (MND) or amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of unknown etiology.[explainmedicine.com]

Epidemiology

  • Epidemiology References: [1] [2] [3] Epidemiological data refers to the US, unless otherwise specified.[amboss.com]
  • SMA with respiratory distress (SMARD1) Inheritance is autosomal recessive due to mutations in the IGHMBP2 gene on chromosome 11q13. [ 9 ] Epidemiology The estimated incidence is between 1 in 6,000 and 1 in 10,000 live births and the carrier frequency[patient.info]
  • Epidemiology of mutations in superoxide dismutase in amyotrophic lateral sclerosis.[ncbi.nlm.nih.gov]
  • .  Epidemiology: Incidence - 1 to 2.7/lakh Prevalence-2.7 to 7.4/lakh Sex predisposition-M F(2:1 to 7:1)(*F M in bulbar onset ALS) Age-Risk increases with age up to 74 years Geographical distribution-In regions likeChamorro people of Guam and Kii[slideshare.net]
  • This was probably due, in large part, to increased life span and better recognition of the diagnosis. 94, 95 More recent population studies from multiple European countries have all demonstrated stable incidence. 1, 5, 42, 55, 81 Many epidemiologic studies[clinicalgate.com]
Sex distribution
Age distribution

Pathophysiology

  • Etiology Pathophysiology Clinical features The most common causes of death among patients with SMA are respiratory insufficiency (due to respiratory muscle weakness ) and aspiration pneumonia (due to bulbar weakness)![amboss.com]
  • Pathophysiology Spinal muscular atrophy (SMA) types I-III Inheritance is autosomal recessive. Affected individuals have two copies of the altered gene. Those who carry one copy are usually unaffected carriers.[patient.info]
  • The following algorithms are available in Special Instructions: -Inherited Motor Neuron Disease Testing Algorithm -Neuromuscular Myopathy Testing Algorithm Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they[mayomedicallaboratories.com]

Prevention

  • Supportive therapy is aimed at preventing respiratory and orthopedic complications. Epidemiology References: [1] [2] [3] Epidemiological data refers to the US, unless otherwise specified.[amboss.com]
  • Respiratory infection Respiratory failure Prognosis Although SMA involves a wide range of disease severity and a high mortality and morbidity rate, recent advances in multidisciplinary supportive care have enhanced quality of life and life expectancy. [ 16 ] Prevention[patient.info]
  • […] disease resulting in neuromuscular junction pathology -Defect specifically in the transmission of nerve impulses to the muscles at the neuromuscular junction -Antibodies block or destroy the receptors that are needed for acetylcholine uptake and this prevents[quizlet.com]
  • These countries included Sudan, Benin, Ethiopia, Burkina Faso, and Nepal, illustrating the importance of continued widespread vaccination prevention programs. 50 Clinical Features In patients with overt manifestations of infection, symptoms consist of[clinicalgate.com]

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!