Neuromuscular syndromes are presented clinically either as a case study or as an overview from the literature, accompanied by text presenting molecular defects, and differential diagnosis.[books.google.com]
The TTN p.Gly30150Asp change is located in the highly conserved titin A-band and not present in any available SNP database.[bmcneurol.biomedcentral.com]
Differential diagnosis and investigation of respiratory muscle weakness according to clinical presentation Patients presenting with respiratory muscle weakness will typically have nocturnal symptoms including orthopnea, sleep disruption, and headache[dovepress.com]
The onset usually occurs in adult life (between the second and fourth decade) but may be congenital or present in early childhood.[medlink.com]
Patients typically present with proximal muscle weakness of legs more than arms, with no sensory involvement.[clevelandclinicmeded.com]
An Italian case of hereditary myopathy with early respiratory failure (HMERF) not associated with the titin kinase domain R279W mutation. Neuromuscul Disord. 2010 Nov;20(11):730-4. doi: 10.1016/j.nmd.2010.07.269. Epub 2010 Aug 13. Tasca G, Udd B.[ghr.nlm.nih.gov]
Myopathy 2 (MMD2) 6 Chromosome 8q22.3; Recessive Epidemiology: 3 Dutch families Gowers (Laing; Early adult onset distal myopathy type III; MPD1) 3, 4 Myosin heavy chain 7 (MYH7) ; Chromosome 14q11.2; Dominant or Sporadic Epidemiology Australian, German, Italian[neuromuscular.wustl.edu]
View Article PubMed Google Scholar Tasca G, Mirabella M, Broccolini A, Monforte M, Sabatelli M, Biscione GL: An Italian case of hereditary myopathy with early respiratory failure (HMERF) not associated with the titin kinase domain R279W mutation.[bmcneurol.biomedcentral.com]
The first Italian family with tibial muscular dystrophy caused by a novel titin mutation . J. Neurol. 257 , 575–579 (2010). 25. Udd, B. , Rapola, J. , Nokelainen, P. , Arikawa, E. & Somer, H.[nature.com]
An Italian case of hereditary myopathy with early respiratory failure (HMERF) not associated with the titin kinase domain R279W mutation.[ncbi.nlm.nih.gov]
Signs and symptoms [ edit ] Some early signs of HIBMs includes: Difficultywalking on heels, and difficulty running; Weak index finger; Frequent loss of balance.[en.wikipedia.org]
95%) Stain for F-actin (Phalloidin) "Necklace" pattern in muscle fibers 38 Muscle fiber splitting: With more severe weakness Vacuoles (50%): Rimmed, blue; With more severe weakness Fiber types: Type 1 predominance (50%) Internal nuclei No necrosis or inflammation[neuromuscular.wustl.edu]
Back to Top Pathophysiology Disruption of the structural integrity and metabolic processes of muscle cells can result from genetic abnormalities, toxins, inflammation, infection, and hormonal and electrolyte imbalances.[clevelandclinicmeded.com]
Genetic Neuromuscular Disorders: A Case-Based Approach is aimed at neuromuscular physicians and neurology residents.[books.google.com]
However, metabolic, inflammatory, toxic and endocrine myopathies present subacutely or even acutely and this requires awareness amongst front-line physicians to recognise and diagnose myopathy.[patient.info]
Design/Methods: Case report Results: A 29-year-old Afghan woman with no family history of muscle disease who developed proximal limbgirdle weakness in her early 20s that slowly progressed to prominent distal weakness and respiratoryinsufficiency (FVC[neurology.org]
Respiratory function test revealed restrictive respiratoryinsufficiency that was treated with nocturnal ventilation support.[bmcneurol.biomedcentral.com]
Falga-Tirado C, Perez-Peman P, Ordi-Ros J, Bofill JM, Balcells E (1995) Adult onset of nemaline myopathy presenting as respiratoryinsufficiency. Respiration 62(6):353–354 PubMed CrossRef Google Scholar 112.[link.springer.com]
Early involvement of the tibialis anterior is also common, except for the Portuguese family, who reported isolated respiratoryinsufficiency and a milder presentation of HMERF.[nature.com]
Differential Diagnosis Late-onset glycogen storage disease type II (GSD II) is characterized by proximal muscle weakness and respiratoryinsufficiency. Inheritance is autosomal recessive.[ncbi.nlm.nih.gov]
In the process of genetic testing of patients with myofibrillar myopathy (MFM) we encountered familial and sporadic cases of skeletal myopathy with or without associated respiratoryabnormalities who lack mutations in MFM-associated genes [ 26, 27 ].[bmcneurol.biomedcentral.com]
Patients typically present with proximalmuscleweakness of legs more than arms, with no sensory involvement.[clevelandclinicmeded.com]
Symmetrical proximalmuscleweakness with absence of sensory symptoms (paraesthesia). Atrophy of muscles (and reduced reflexes) occurs late with myopathies (early with neuropathy).[patient.info]
Keywords Myopathy Respiratory failure HMERF Titin Titin A-band mutation Fibronectin type III Background Hereditary myopathy with early respiratory failure (HMERF) also known as Edström myopathy is a disorder manifesting with predominantly proximalmuscle[bmcneurol.biomedcentral.com]
Differential Diagnosis Late-onset glycogen storage disease type II (GSD II) is characterized by proximalmuscleweakness and respiratory insufficiency. Inheritance is autosomal recessive.[ncbi.nlm.nih.gov]
Neurologic exam revealed thinning of the anterior legs, bilateral calfhypertrophy, neck flexor and extensor weakness, distal greater than proximal weakness in the legs, and proximal weakness in the arms. CK level was mildly elevated at 318 U/L.[neurology.org]
There was wasting of the trapezius, sternocleidomastoid and calf muscles, but each patient had initially bilateral calfhypertrophy (Table 1 ).[bmcneurol.biomedcentral.com]
In the muscular dystrophies, which tend to manifest in childhood or adolescence, dyspnea, cardiac abnormalities, contractures, scapular winging, calfhypertrophy, and skeletal deformities may be present in addition to slowly progressive weakness.[clevelandclinicmeded.com]
Typically, patients present with lowerlimbmuscleweakness, which slowly spreads to involve truncal, neck-flexor, facial, bulbar, and respiratory muscles. Distribution of the weakness may be distal or both proximal and distal.[medlink.com]
The patient’s mother had suffered from slowly progressing predominantly lowerlimbmuscleweakness from the age of 50 years, subsequently developed respiratory insufficiency necessitating ventilatory support at the age of 70, and died two years later[bmcneurol.biomedcentral.com]
This process is usually due to mutations in the TTN (titin) gene, located on the longarm of chromosome 2 (2q31.2); however, in rare cases, people with the characteristics of HMERF do not have mutations identified in this gene and the cause of the disease[ivami.com]
Key points for each genetic disease are identified to suggest treatment, when available, or the main clinical exams useful in follow-up of patients.[books.google.com]
Two reports by Palmio et al 1 and Pfeffer et al 2 suggest that hereditary myopathy with early respiratory failure (HMERF) may not be rare and is distributed worldwide.[jnnp.bmj.com]
This suggests that the p.Arg32450Trp mutation affects the ability of titin to control muscle protein turnover and through this action disrupts muscle sarcomere maintenance.[bmcneurol.biomedcentral.com]
Acuteness of symptoms: Weakness over hours suggests a toxic cause or episodic paralysis. Weakness developing over days - consider dermatomyositis or rhabdomyolysis. Weakness over weeks suggests polymyositis, steroid myopathy, endocrine myopathy.[patient.info]
These results suggested that this rare mutation in TTN segregated with the disease in this family.[nature.com]
Some affected individuals have weakness of muscles of the lower leg and foot, which makes it difficult to lift the toes while walking, a condition known as footdrop.[ghr.nlm.nih.gov]
Her gait was waddling and she had bilateral footdrop. No muscle atrophies or hypertrophies were observed (Table 1 ). CK levels were 2-fold-increased.[bmcneurol.biomedcentral.com]
drop Hypotonia Weakness: Intrafamilial variation Legs Ankle dorsiflexion: Often severe with footdrop Hanging big toe Proximal muscles may be involved Neck: Sternocleidomastoids & Neck flexors Hands Finger (esp 5th) & Wrist extensors Onset age: 3rd to[neuromuscular.wustl.edu]
drop can be through the use of Ankle Foot Orthoses (AFOs) which can be designed or selected by an Orthotist based upon clinical need of the individual.[en.wikipedia.org]
GNE-related myopathy (IBM2) typically presents in the late teens to early adulthood with slowly progressive distal muscle weakness involving gait disturbance and footdrop secondary to anterior tibialis muscle weakness.[invitae.com]
Electro diagnostic study showed evidence of a generalized myopathy with irritability. MRI of the lower extremities revealed characteristic fatty infiltration mostly affecting the semitendinosus, quadriceps, and tibialis anterior muscles.[neurology.org]
Variable in families: Some patients severely disabled, others mildly affected Respiratory failure: Some patients Tendon reflexes: Absent Pes cavus Tremor (30%) Laboratory Seum CK: Normal, or Mildly elevated (Up to 4x) EMG: Mixed features Myogenic & Irritable[neuromuscular.wustl.edu]
gait; Foot drop Hypotonia Weakness: Intrafamilial variation Legs Ankle dorsiflexion: Often severe with foot drop Hanging big toe Proximal muscles may be involved Neck: Sternocleidomastoids & Neck flexors Hands Finger (esp 5th) & Wrist extensors Onset[neuromuscular.wustl.edu]
Waddlinggait of Duchenne muscular dystrophy at age 3-6 years is typical. Acuteness of symptoms: Weakness over hours suggests a toxic cause or episodic paralysis. Weakness developing over days - consider dermatomyositis or rhabdomyolysis.[patient.info]
Key points for each genetic disease are identified to suggest treatment, when available, or the main clinical exams useful in follow-up of patients.[books.google.com]
You may need treatment in intensive care unit at a hospital. Chronic respiratory failure can often be treated at home. But if your chronic respiratory failure is severe, you might need treatment in a long-term care center.[medlineplus.gov]
In acquired myopathies, treatment is targeted toward the underlying cause. Treatment of statin myopathies is dependent on creatine phosphokinase levels and degree of muscle symptoms. Consider lower doses when initiating statin therapy.[clevelandclinicmeded.com]
You may receive oxygen therapy and other treatment to help you breathe. NIH: National Heart, Lung, and Blood Institute Acute respiratory distress syndrome (Medical Encyclopedia) Respiratory acidosis (Medical Encyclopedia) [ Read More ][icdlist.com]
Another protein, neural cell adhesion molecule is under-sialyated in people with IBM, but as of 2016 it had no known role in muscle function. [1] Treatment [ edit ] Treatment is palliative, not curative (as of 2009). [16] Treatment options for lower limb[en.wikipedia.org]
Prognosis This depends on the specific diagnosis. The primary disorders are incurable conditions with varied prognosis. Secondary myopathy may be corrected by treating the underlying cause.[patient.info]
Prognosis [ edit ] A 2009 review noted that muscle weakness usually begins after age 20 and after 20–30 years, the person usually requires a wheel chair for mobility.[en.wikipedia.org]
Prognosis of amyotrophic lateral sclerosis with respiratory onset. J Neurol Neurosurg Psychiatry. 2007;78(6):629–631. 10. Brooks BR, Miller RG, Swash M, Munsat TL.[dovepress.com]
In cases suspected to be a primary inflammatory myopathy, specific autoantibodies can be considered to determine the prognosis and rule out associated conditions.[clevelandclinicmeded.com]
ALS with respiratory onset: Clinical features and effects of non-invasive ventilation on the prognosis. Amyotroph Lateral Scler. 2010; 11 :379–82. [ PubMed : 20001486 ] Hedberg C, Melberg A, Dahlbom K, Oldfors A.[ncbi.nlm.nih.gov]
Rhabdomyolysis may also be seen with infectious etiologies, alcohol, and toxic exposures.[clevelandclinicmeded.com]
Carrillo N, Malicdan MC, Huizing M (2018) GNE myopathy: Etiology, diagnosis, and therapeutic challenges. Neurotherapeutics doi: 10.1007/s13311-018-0671-y "Inclusion body myopathy 3". NIH Genetic and Rare Diseases Information Center.[en.wikipedia.org]
However, the underlying genetic etiology in this family was unknown. The aim of this study was to determine the genetic cause in this family. To identify the responsible genetic mutation, we performed linkage analysis and whole-exome sequencing.[nature.com]
Oculopharyngodistal myopathy This condition is associated with both autosomal dominant and recessive inheritance, and the genetic etiology is unknown. 12 Respiratory failure in ambulant patients is common in this condition, and clinical presentation includes[dovepress.com]
Prevalence The prevalence of HMERF is not known, but it is most likely underrecognized because of its broad phenotypic spectrum and the very recent discovery of its underlying genetic etiology.[ncbi.nlm.nih.gov]
: 3 Dutch families Gowers (Laing; Early adult onset distal myopathy type III; MPD1) 3, 4 Myosin heavy chain 7 (MYH7) ; Chromosome 14q11.2; Dominant or Sporadic Epidemiology Australian, German, Italian & Austrian families Genetics: MYH7 mutations Types[neuromuscular.wustl.edu]
Epidemiology These are all relatively uncommon diseases: Duchenne muscular dystrophy is easily the most common childhood-onset muscular dystrophy and affects 1 in 3,300 boys. [ 6 ] The prevalence of Duchenne muscular dystrophy is 63 cases per million.[patient.info]
Table 1 Clinical Features of Common Myopathies Myopathy Epidemiology Distribution of Weakness Other Systemic Manifestations Acquired Myopathies Dermatomyositis Female male Peak incidence: children and ages 40–60 yr Symmetrical proximal muscle weakness[clevelandclinicmeded.com]
Jones & Jianbo Yao Canine Genetics and Epidemiology (2017) Performance comparison of two commercial human whole-exome capture systems on formalin-fixed paraffin-embedded lung adenocarcinoma samples Silvia Bonfiglio , Irene Vanni , Valeria Rossella , Anna[nature.com]
The pathophysiology is still unclear. Cardiac involvement may occur.[en.wikipedia.org]
Back to Top Pathophysiology Disruption of the structural integrity and metabolic processes of muscle cells can result from genetic abnormalities, toxins, inflammation, infection, and hormonal and electrolyte imbalances.[clevelandclinicmeded.com]
Prevention Genetic counselling is, in some of the most common myopathies such as Duchenne muscular dystrophy, the only intervention that can prevent disease. In general: Give genetic counselling early.[patient.info]
In patients with an underlying metabolic myopathy, education about following a more moderate exercise program and avoiding intense exercise and fasting is necessary in preventing recurrent episodes.[clevelandclinicmeded.com]
Some of these conditions have disease-modifying treatment available, but even in the absence of such therapy, the management of respiratory failure with supportive care such as NIV and cough assist is recommended to improve quality of life and prevent[dovepress.com]
Exercises and activities suggested by physiotherapy consultation may be helpful to prevent continued loss of physical function due to inactivity.[ncbi.nlm.nih.gov]