Our report underscores the consideration of contiguous gene deletion in children with ANM who present with congenital hypotonia and cardiomyopathy. [nlm.medscape.idmu.unboundmedicine.unboundmedicine.com]

The latter is of particular interest in the present context. [books.google.com]

Muscle weakness and contractures can be present early and are progressive. Motor development is delayed and may be limited to rolling from side-to-side. [wohproject.org]

The present study further investigates the expression and fate of mutant slow TnT in muscle cells. Intact slow TnT mRNA was readily detected in patient muscle, indicating unaffected transcription and RNA splicing. [ncbi.nlm.nih.gov]

Definition / general One of the most common non dystrophic congenital myopathies, with a heterogeneous clinical presentation and characteristic rod-like inclusions (nemaline bodies) within myofibers Essential features Skeletal muscle with red to purple [pathologyoutlines.com]

• Hemophilia A

  Ganglioside GM3 synthase (alpha 2,3-sialytransferase) deficiency 609056 Gaucher disease 230800 Glucose/galactose malabsorption 606824 Glutaric acidemia (glutary1-CoA dehydrogenase deficiency) 231670 Gorlin syndrome 109400 Hallervorden-Spatz disease 234200 Hemophilia [ddcclinic.org]

  A H +306900 Hemophilia B A #609310 Hereditary non-polyposis colon cancer OCM #600155 Hirschsprung disease 2 OOM M #236250 Homocystinuria A #607748 Hypercholanemia, familial A Hypertension A M H #241500 Hypophosphatasia OCM H #218700 Hypothyroidism and [biochemgenetics.ca]

• Weakness

  RESULTS: The child had congenital onset of severe, diffuse weakness that remained fairly static for five years. Exam showed ptosis and facial weakness as well as marked proximal and distal limb weakness. [neurology.org]

  Introduction : Nemaline myopathy (NM) is a congenital neuromuscular disorder often characterized by hypotonia, facial weakness, skeletal muscle weakness, and the presence of rods on muscle biopsy. [pubfacts.com]

  INTRODUCTION: Nemaline myopathy (NM) is a congenital neuromuscular disorder often characterized by hypotonia, facial weakness, skeletal muscle weakness, and the presence of rods on muscle biopsy. [ncbi.nlm.nih.gov]

• Feeding Difficulties

  Morbidity from respiratory tract infections and feeding difficulties frequently diminished with increasing age. Aggressive early management is warranted in most cases of congenital nemaline myopathy. ...read moreread less [typeset.io]

  Muscle weakness may also cause difficulty speaking (dysarthria) and swallowing resulting in feeding difficulties. Some infants with nemaline myopathy may require a feeding tube. [rarediseases.org]

  Dysarthria and feeding difficulties are common. Respiratory problems secondary to involvement of the diaphragm and intercostal muscles are common. [egl-eurofins.com]

  Typical congenital NM (45 % of all individuals with NM) is often evident at birth or during the first year of life with hypotonia, muscle weakness and feeding difficulties. [mgz-muenchen.de]

• Respiratory Insufficiency

  Delayed motor skills 0002194 Infantile onset Onset in first year of life Onset in infancy [ more ] 0003593 Myopathy Muscle tissue disease 0003198 Nemaline bodies 0003798 Respiratory insufficiency Respiratory impairment 0002093 Rigidity Muscle rigidity [rarediseases.info.nih.gov]

  Affected infants display tremors with hypotonia and mild contractures of the shoulders and hips; proximal contractures progressively weaken and a pectus carinatum develops before infants die of respiratory insufficiency, often by age 2. [medical-dictionary.thefreedictionary.com]

  Progressive worsening of the proximal contractures, weakness, and a pectus carinatum deformity develop before the children die of respiratory insufficiency, usually in the second year. [wwww.unboundmedicine.com]

  Proximal contractures progressively weaken and a pectus carinatum deformity develops before children die of respiratory insufficiency, usually in the second year. [ghr.nlm.nih.gov]

• Nasal Voice

  Patients often have an expressionless face and a nasal voice due to the affected facial and bulbar muscles. Respiratory involvement is less prominent but may be subclinical, manifesting as frequent lower respiratory tract infections. [mgz-muenchen.de]

  Consequently, patients with this genetic mutation often cannot lift their heads and speak with a nasal voice. [en.wikipedia.org]

• Muscle Rigidity

  […] tissue disease 0003198 Nemaline bodies 0003798 Respiratory insufficiency Respiratory impairment 0002093 Rigidity Muscle rigidity 0002063 Showing of 20 | Last updated: 12/1/2018 Making a diagnosis for a genetic or rare disease can often be challenging [rarediseases.info.nih.gov]

• Hypotension

  History of tuberculosis History of malignancy History of other autoimmune disease Hypotension Hyperpigmentation Auricular−cartilage calcification Vitiligo Electrolyte abnormalities Hypoglycemia Normal Normal Normal Hyperaldosteronism with myopathy [6 [wikidoc.org]

• Myopathy

  Disease description A form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. [uniprot.org]

  MeSH terms Alternative Splicing Amino Acid Sequence Animals Cell Line Codon, Nonsense Humans Infant Mice Molecular Sequence Data Muscle Fibers, Slow-Twitch/physiology* Mutation, Missense* Myopathies, Nemaline*/genetics Myopathies, Nemaline*/metabolism [ncbi.nlm.nih.gov]

  Pathology by systems > Locomotory system > Muscles > nemaline myopathies Synopsis nemaline myopathy nemaline cardiomyopathy Associations radiotherapy ( 14506646 ) Etiology NEM1: autosomal dominant nemaline myopathy (NEM1) (MIM.161800) - mutations in the [humpath.com]

  Amish nemaline myopathy and dilated cardiomyopathy caused by a homozygous contiguous gene deletion of TNNT1 and TNNI3 in a Mennonite child. [nlm.medscape.idmu.unboundmedicine.unboundmedicine.com]

• Muscle Weakness

  People with the childhood-onset type usually develop muscle weakness in adolescence. The adult-onset type is the mildest of all the various types. People with this type usually develop muscle weakness between ages 20 and 50. 2. [encyclopedia.pub]

  weakness than the other forms, with most individuals being able to eventually walk independently Severe Congenital (Neonatal) Nemaline Myopathy : apparent at birth, with profound muscle weakness, severe hypotonia, and life-threatening complications, [patientworthy.com]

  Muscle weakness, low muscle tone, and trouble eating are the usual signs. Some patients may have difficulties with breathing but this is not true for all patients. [thinkgenetic.com]

  Introduction : Nemaline myopathy (NM) is a congenital neuromuscular disorder often characterized by hypotonia, facial weakness, skeletal muscle weakness, and the presence of rods on muscle biopsy. [pubfacts.com]

• Fracture

  Another patient who, in all other respects, fitted into the typical congenital subgroup, had multiple congenital fractures. Fractures in later life occurred in 13 cases, often after minor trauma. [zdoc.site]

  […] forms, with most individuals being able to eventually walk independently Severe Congenital (Neonatal) Nemaline Myopathy : apparent at birth, with profound muscle weakness, severe hypotonia, and life-threatening complications, such as cardiomyopathy, fractures [patientworthy.com]

  Atypical features in a minority of cases included arthrogryposis, central nervous system involvement, and congenital fractures. Progressive distal weakness developed in a minority of patients. [typeset.io]

  Like patients with the intermediate form of NM spontaneous movements are present but no contractures or fractures. Patients often have an expressionless face and a nasal voice due to the affected facial and bulbar muscles. [mgz-muenchen.de]

  Bone fractures. Cardiomyopathy. Respiratory failure. Intermediate congenital nemaline myopathy Many people need breathing support and a wheelchair. [my.clevelandclinic.org]

• Myalgia

  Swelling Tender Erythema and induration Alcohol intoxication Change in mental status Telangiectasia Peripheral neuropathy Monspecific and are normal in many patients Normal or ↑↑ Normal Normal Organ system Disease Age of onset Muscle weakness Fever Myalgia [wikidoc.org]

  A typical hallmark of this kind of NM may be myalgia. Respiratory and cardiac involvement is uncommon but, when present, often occurs in association with increasing weakness and physical disability. [mgz-muenchen.de]

  Muscle pain (myalgia) may also occur. Involvement of certain neck muscles may make it difficult to hold one’s head up and cause the head to drop. [rarediseases.org]

  Symptoms such as lower limb weakness, dyspnea and myalgia developed rapidly in 7 cases during adulthood. Three of these patients displayed rapid clinical progression and acute respiratory insufficiency, while their prognosis was poor. [spandidos-publications.com]

  When surveyed, additional infrequent muscle complaints reported included myalgias (7 of 33, 21%) and muscle slowness (2 of 31, 6.5%). [n.neurology.org]

• Muscle Hypotonia

  Nemaline myopathy (NM) is a congenital myopathy first described in 1963 by Shy and Conen, characterized by hypotonia and general muscle weakness predominantly in facial muscles, cervical and trunk flexor muscles, foot dorsiflexor muscles and finger extensor [scielo.br]

• Tremor

  Clinical Characteristics General description (for patients): Amish nemaline myopathy presents in the newborn period with tremors, especially in muscles of the jaw and lower limbs. [wohproject.org]

  Fogel Elsevier Health Sciences, ٠٦‏/١١‏/٢٠١٣ - 281 من الصفحات 0 مراجعات This issue of Neurologic Clinics features a review of clinical neurogenetics as it pertains to the following disorders: Huntington Disease; Autism/ASD;Fragile X Tremor Ataxia Syndrome [books.google.com]

  Clinical description It has a neonatal onset and patients present with hypotonia associated to contractures, a severe pectus carinatum, and tremor that subsides after 2-3 months of age. Etiology TNNT1 (19q13.4) is the causative gene of the Amish NM. [rarediseases.info.nih.gov]

  Affected infants display tremors with hypotonia and mild contractures of the shoulders and hips; proximal contractures progressively weaken and a pectus carinatum develops before infants die of respiratory insufficiency, often by age 2. [medical-dictionary.thefreedictionary.com]

  A rare form of nemaline myopathy known as Amish Nemaline Myopathy has only been seen in a genetically isolated cohort of Old Order Amish patients who may additionally present with tremors in the first 2-3 months of life. [ncbi.nlm.nih.gov]

• Dysarthria

  Dysarthria and feeding difficulties are common. Respiratory problems secondary to involvement of the diaphragm and intercostal muscles are common. [egl-eurofins.com]

  Dysarthria and dysphagia are common; deep tendon reflexes are depressed or absent. [mgz-muenchen.de]

  Some infants may have an abnormal waddling walk (gait), swallowing difficulties (dysphagia), speech difficulties (dysarthria), and a nasal tone to the voice. [rarediseases.org]

  Difficulty speaking (dysarthria) and swallowing (dysphagia). Displaced jaw, farther back than normal (retrognathia). Elongated face. Extremely arched roof of the mouth. Nasally speech (velopharyngeal dysfunction). [my.clevelandclinic.org]

• Absent Deep Tendon Reflexes

  Company Science NGS Panel – Genetic Testing for Nemaline Myopathy Nemaline myopathy (NEM, NM) is one of the most common congenital myopathies characterized by hypotonia, weakness and absent deep tendon reflexes. [centogene.com]

  NM is characterized by weakness, hypotonia, and depressed or absent deep tendon reflexes. Muscle weakness is usually most severe in the face, the neck flexors, and the proximal limb muscles. [egl-eurofins.com]

  deep tendon reflexes and nemaline bodies (rods) on skeletal muscle biopsy. [els.net]

Treatment: No treatment is available for the primary disease. Prognosis: Death commonly results from respiratory insufficiency in the second year of life. [wohproject.org]

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional. [rarediseases.info.nih.gov]

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment Official Title: Treatment of TNNT1-Myopathy With L-Tyrosine. [clinicaltrials.gov]

No proven effective therapy other than symptomatic treatment Symptomatic treatment has shown to be helpful in many patients ( Semin Pediatr Neurol 2011;18:230 ) Mechanical nighttime ventilation Orthoses Nasogastric feeding and nutritional support Aggressive [pathologyoutlines.com]

Management and Treatment How is nemaline myopathy treated? Nemaline myopathy treatment focuses on reducing your symptoms. Treatments may include: Continuous positive airway pressure (CPAP) therapy, to help improve breathing during sleep. [my.clevelandclinic.org]

Prognosis Life expectancy rarely exceeds 2 years as a consequence of severe respiratory insufficiency. Visit the Orphanet disease page for more resources. [rareguru.com]

Prognosis: Death commonly results from respiratory insufficiency in the second year of life. [wohproject.org]

DIP ) Pathway : Protein interactions : P13805 Tissue (According to GeneNote, PubMed, HPA ) Tissue expression: PubMed Reference Human Protein Atlas (HPA): CAB015168 Clinical (According to OMIM, PubMed ) OMIM : 191041 PubMed: Early detection Diagnosis Prognosis [actrec.gov.in]

Prognosis Life expectancy rarely exceeds 2 years as a consequence of severe respiratory insufficiency. Last updated: 10/10/2011 This table lists symptoms that people with this disease may have. [rarediseases.info.nih.gov]

Three of these patients displayed rapid clinical progression and acute respiratory insufficiency, while their prognosis was poor. [spandidos-publications.com]

Pathology by systems > Locomotory system > Muscles > nemaline myopathies Synopsis nemaline myopathy nemaline cardiomyopathy Associations radiotherapy ( 14506646 ) Etiology NEM1: autosomal dominant nemaline myopathy (NEM1) (MIM.161800) - mutations in the [humpath.com]

Etiology TNNT1 (19q13.4) is the causative gene of the Amish NM. Genetic counseling Transmission follows an autosomal recessive pattern. Prognosis Life expectancy rarely exceeds 2 years as a consequence of severe respiratory insufficiency. [rareguru.com]

Genetics The understanding of the genetic etiology of NM is continuing evolve. To this date 12 genes have been linked to Nemaline Myopathy (ACTA1, CFL2, KBTBD13, KHLH40, KHLH41, LMOD3, MYBN, NEB, TNNT1, TNNT3, TPM2, TPM3). [childrenshospital.org]

Although ten genes have been implicated in the etiology of NM, an important number of patients remain without a molecular diagnosis. [content.iospress.com]

Genealogic epidemiology of inbreeding. Am. J. Epidemiol. 125:453-461. Khoury, MT, B.H. Cohen, E.L. Diamond et al. 1987c. Inbreeding and prereproductive mortality in the Old Order Amish II. Genealogic epidemiology of prereproductive mortality. Am. J. [the-medical-dictionary.com]

Relevant External Links for TNNT1 Genetic Association Database (GAD) TNNT1 Human Genome Epidemiology (HuGE) Navigator TNNT1 Atlas of Genetics and Cytogenetics in Oncology and Haematology: TNNT1 No data available for Genatlas for TNNT1 Gene Close physical [genecards.org]

In China, only a few NM cases were reported, and related epidemiological data have not yet become available. [spandidos-publications.com]

Epidemiology Frequency The true incidence of congenital myopathies is unknown as no large population-based studies have been conducted. However, there are a varied number of stuidies that demonstrate a relative incidence of the diseases. [emedicine.medscape.com]

[…] severity Most common mutations are NEB (recessive) and ACTA1 (dominant) Terminology Nemaline myopathy (NM), nemaline rod myopathy "Nemaline" means thread-like, describes the appearance of rods ( Semin Pediatr Neurol 2011;18:230 ) Greek nema = thread Pathophysiology [pathologyoutlines.com]

Jin’s main research interest is in gene regulation, structure-function relationship and pathophysiological adaptation of contractile and cytoskeleton proteins. Research in Dr. [obgyn.med.wayne.edu]

Genetic analyses are necessary to further investigate the pathophysiology of the observed clinical and pathological features of these patients. [spandidos-publications.com]

[…] subtypes: central core and multiminicore myopathy); centronuclear myopathy (subtypes: myotubular myopathy and autosomal centronuclear myopathy); congenital fiber-type disproportion myopathy; myosin storage myopathy; and nonspecific myopathic changes Pathophysiology [emedicine.medscape.com]

Unfortunately for nemaline myopathy, there are barriers that will prevent this exact gene therapy approach from being used. [nemaline.org]

There is no cure for NEM to date, but a number of procedurescould significantly improve the quality of life 1, 15 : Treatment of lower respiratory tract infections Ventilator use for nocturnal hypoxia Special feeding techniques Physical therapy to help prevent [centogene.com]

A feeding tube prevents this from happening. There are a number of different types of feeding tube which are available, and these are fitted by a short surgical procedure. [gofundme.com]

Such therapy is aimed at preserving muscle strength and function and to prevent the development of contractures. In addition, respiratory support may be necessary, potentially including mechanical ventilation to prevent nocturnal hypoventilation. [rarediseases.org]