Symptoma

Nemaline Myopathy Type 4

NM4

Results: Our patient presented at birth with hypotonia and weakness, and subsequently developed respiratory failure in infancy. He is ambulatory but has increasing fatigue requiring a wheelchair by mid-afternoon. [omicsonline.org]

Subsarcolemmal caps were present in 6-10% of the fibres and immunoreactive with anti-tropomyosin antibodies. [ncbi.nlm.nih.gov]

In the second part of the project we performed a deep morphological analysis in our cohort of more than 100 patients presenting a congenital myopathy and we identified homogeneous cohorts of patients presenting neonatal or antenatal onset congenital myopathies [theses.fr]

Within families, there can be considerable variation with respect to disease presentation and degree of muscle involvement. The serum creatine kinase (CK) levels are either normal or usually mildly elevated. [neurology.mhmedical.com]

  • Feeding Difficulties

    The CM clinical spectrum ranges from severe forms presenting with congenital hypotonia, delayed motor milestones, feeding difficulties, muscle weakness, facial muscle involvement, and ophtalmoplegia (including progressive scoliosis chronic respiratory [centrodinoferrari.com]

    Many affected infants have feeding difficulties and about 25-40% of infants with congenital NM die, often from respiratory failure. [genedx.com]

    Management and treatment A multidisciplinary approach is needed to handle respiratory insufficiency (permanent or intermittent use of mechanical ventilation and treatment of lower respiratory tract infections) and feeding difficulties (feeding techniques [orpha.net]

    The most common form of NM is the typical congenital form, which presents in infancy or early childhood with hypotonia, static or slowly progressive muscle weakness, and feeding difficulties. [invitae.com]

    difficulties Uncommon - Between 30% and 50% cases Autosomal recessive inheritance Uncommon - Between 30% and 50% cases Accelerate your rare disease diagnosis with us Learn more Other less frequent symptoms Patients with Scoliosis and Arrhythmia. may [mendelian.co]

  • Pathologist

    PMID: 23413262 Assay Assay and technical information Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion [invitae.com]

  • Death in Infancy

    […] in infancy Central hypotonia Micrognathia Cognitive impairment Anteverted nares Long philtrum Narrow mouth Hyperhidrosis Camptodactyly of finger Wide nose Difficulty running Facial palsy Generalized amyotrophy Pulmonary embolism Skin ulcer Hemiparesis [mendelian.co]

    In contrast to NEM, severe cases with death in infancy are rare in cap myopathy. Only one case of severe cap myopathy, associated with death at the fifth year of life has been reported. This patient carried an ACTA1 mutation [12]. [kundoc.com]

  • Difficulty Walking

    The muscle weakness slowly worsens over time and can lead to delayed development of motor skills, such as crawling or walking; muscle pain during exercise; and difficulty walking. [icdlist.com]

  • Failure to Thrive

    Failure to thrive necessitated nasogastric tube feeding at ten months followed by gastrostomy insertion at 13 months of age. CK levels as well as ECG were normal. [content.iospress.com]

    Nemaline rods and complex I deficiency in three infants with hypotonia, motor delay and failure to thrive. [ncbi.nlm.nih.gov]

  • Hypertension

    […] and Sinusitis, related diseases and genetic alterations Hypertension and Neurological speech impairment, related diseases and genetic alterations [mendelian.co]

    […] invasive ventilation; HV, central hypoventilation; RH#, mild restricted right cardiac function; VI, mild valve insufficiencies; LV", minor left ventricular hypertrophy; AD, borderline aortic dilatation; EF#, reduction of ejection fraction; AH, arterial hypertension [kundoc.com]

    She was otherwise known for obesity, hypertension and past history of seizures. [ojrd.biomedcentral.com]

  • Mitral Valve Prolapse

    valve prolapse Anal atresia Lumbar hyperlordosis Frequent falls Reduced tendon reflexes Nasal speech Poor head control Gowers sign Easy fatigability Toe walking Neurological speech impairment Dilatation Waddling gait Type 1 muscle fiber predominance [mendelian.co]

  • Muscle Hypotonia

    The main clinical manifestations include weakness (usually most severe in the face, the neck flexors and the proximal limb muscles), hypotonia and depressed or absent deep tendon reflexes. [orpha.net]

    Muscle hypotonia since birth was present in all cases. The other clinical findings reported were skeletal or facial dysmorphisms, breastfeeding difficulties and respiratory failure ( Table ). [scielo.br]

  • Muscle Weakness Congenital

    The most common presenting symptoms are hypotonia and muscle weakness. [invitae.com]

  • Myopathic Facies

    Clinical signs : hypotonia mainly at the level of the proximal muscles and the muscles of the neck, arched palate, myopathic facies, progressive respiratory insufficiency. Occasionally: micrognathia, scoliosis. CPK level normal or low. [sites.uclouvain.be]

  • Onset in Infancy or Childhood

    […] in those with RYR1 mutations Core–rod myopathy AD/AR AR AD α-Actin 1 ( ACTA1 ) Nebulin ( NEB ) Kelch repeat and BTB/ ( KBTBD13 ) Onset in infancy or childhood. [neurology.mhmedical.com]

    Clinical features of cap myopathy are onset in infancy or childhood, mainly proximal and axial muscle weakness, a long myopathic face with high arched palate, skeletal deformities, such as scoliosis, and respiratory problems. [kundoc.com]

  • Limb Weakness

    Based upon the subtype, the degree of limb weakness does not always correlate to the severity of respiratory weakness. [emedicine.medscape.com]

    At the age of 45 years, she presented with a waddling gait and a mild proximal and distal lower limb weakness, resulting in problems to run and difficulties to climb the stairs. She walked unassisted without distance limitation. [kundoc.com]

  • Gowers Sign

    sign Easy fatigability Toe walking Neurological speech impairment Dilatation Waddling gait Type 1 muscle fiber predominance Generalized muscle weakness Abnormality of the cardiovascular system Progressive muscle weakness Scapular winging EMG: myopathic [mendelian.co]

    He did not show a Gowers’ sign. Symmetrical weakness was present in neck flexors (4/5), 119 deltoid muscles (4/5), scapulo-humeral muscles, resulting in scapular winging (Fig. 1E), and in feet extensors (4/5). [kundoc.com]

  • Gowers Sign

    sign Easy fatigability Toe walking Neurological speech impairment Dilatation Waddling gait Type 1 muscle fiber predominance Generalized muscle weakness Abnormality of the cardiovascular system Progressive muscle weakness Scapular winging EMG: myopathic [mendelian.co]

    He did not show a Gowers’ sign. Symmetrical weakness was present in neck flexors (4/5), 119 deltoid muscles (4/5), scapulo-humeral muscles, resulting in scapular winging (Fig. 1E), and in feet extensors (4/5). [kundoc.com]

  • Hyporeflexia

    Diagnosis is made based upon clinical signs such as muscle weakness, absent or low deep tendon reflexes (hyporeflexia), and a high-arched palate, along with electron-dense aggregates, called nemaline rods, being observed at the microscopic level within [en.wikipedia.org]

Look out for: scoliosis, kyphosis, cronic ear infections (tubes often needed) Recommended: annual sleep study, swallow study/study of aspiration, nutritionist workup, cranial/facial follow-up, endocrine work-up, baseline cardiologist work-up and follow-up [nemaline.org]

  • Right Axis Deviation

    Electrocardiography showed no significant abnormalities except for a right axis deviation in the index patient and her son. [kundoc.com]

Treatment must continue throughout life, as there is no known cure. It is important to diagnose early and start treatment quickly since there is usually no repair to damage that has occurred to brain, eyes, bones, and ears. [rheumatology.org]

Management and treatment A multidisciplinary approach is needed to handle respiratory insufficiency (permanent or intermittent use of mechanical ventilation and treatment of lower respiratory tract infections) and feeding difficulties (feeding techniques [orpha.net]

No effective treatment is known. [en.wikipedia.org]

We will not be successful in finding a treatment or cure unless we know who the affected individuals are, what the diagnosis is and how the disease is affecting the individual. [cmdir.org]

These is insufficient scientific evidence of the effectiveness of these treatments. [ncbi.nlm.nih.gov]

Prognosis Prognosis depends on the NM type, and life expectancy ranges from few months to a near-normal lifespan. The documents contained in this web site are presented for information purposes only. [orpha.net]

We highlight the severe neonatal forms (nemaline, X-linked myotubular) to be identified early to establish prognosis and provide appropriate genetic counseling. [ncbi.nlm.nih.gov]

The 3 most common types of congenital myopathy, in order, are Central core and multiminicore myopathies (core myopathies) Centronuclear myopathy Nemaline myopathy The types are distinguished primarily by their histologic features, symptoms, and prognosis [msdmanuals.com]

Adult-onset NM is usually sporadic ( Etiology Seven genes involved in muscle thin filament structure and function, have been linked to NM: NEB (2q22), TPM2 (9p13), TPM3 (1q21.2), ACTA1 (1q42.13), TNNT1 (19q13.4), CFL2 (14q12) and KBTBD13 (15q22.31). [orpha.net]

(Etiology) Cap Myopathy can be caused by mutations in the ACTA1, TPM2, or TPM3 genes This condition follows an autosomal dominant manner of inheritance, however, most cases are not inherited; they result from new mutations in the gene and occur in people [dovemed.com]

Diagnosis and etiology of congenital muscular dystrophy: We are halfway there. Annals of Neurology, 80(1), 101-111. [sydney.edu.au]

We propose that gene panels should be used as a first-tier test in patients with suspected muscle disorders of undetermined etiology. [ojrd.biomedcentral.com]

As such, consideration for the specific etiology is needed. Additionally, many infants/neonates with congenital myopathy can make improvements in the first few years of life. [emedicine.medscape.com]

[…] amyotrophy Precursor T-cell acute lymphoblastic leukemia Translocation renal cell carcinoma Synonym(s): - Cap disease Classification (Orphanet): - Rare genetic disease - Rare neurologic disease Classification (ICD10): - Diseases of the nervous system - Epidemiological [csbg.cnb.csic.es]

Summary Epidemiology Annual incidence has been estimated at 1/50,000 live births in a Finnish study but the disease is more common in the Amish community. Clinical description The age of onset varies from birth to adulthood. [orpha.net]

Relevant External Links for TPM3 Genetic Association Database (GAD) TPM3 Human Genome Epidemiology (HuGE) Navigator TPM3 Atlas of Genetics and Cytogenetics in Oncology and Haematology: TPM3 No data available for Genatlas for TPM3 Gene Mutations of tropomyosin [genecards.org]

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]

東京都立小児総合医療センター神経内科 Department of Neurology, Tokyo Metropolitan Children’s Medical Center  Tokyo, Japan 3 国立精神・神経医療研究センター神経研究所疾病研究第一部 Department of Neuromuscular Research, National Center of Neurology and Psychiatry  Tokyo, Japan 4 東京医科大学病態生理学分野 Department of Pathophysiology [jpccs.jp]

How can Cap Myopathy be Prevented? Cap Myopathy may not be preventable, since it is a genetic disorder. [dovemed.com]

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]