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]

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]

The index patient presented a long narrow face, high arched palate, discrete micrognathia (Fig. 1B), scoliosis and scapula alata (Fig. 1D). She did not present facial weakness, ophthalmoparesis, or ptosis. [kundoc.com]

• Feeding Difficulties

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

  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]

  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]

  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]

  Feeding difficulties in infancy MedGen UID: 436211 •Concept ID: C2674608 • Finding Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking [ncbi.nlm.nih.gov]

• Difficulty Walking

  Difficulty walking MedGen UID: 86319 •Concept ID: C0311394 • Finding Any persistent problem with walking. Myopathic facies MedGen UID: 90695 •Concept ID: C0332615 • Finding A facial appearance characteristic of myopathic conditions. [ncbi.nlm.nih.gov]

  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]

• Respiratory Abnormalities

  Examination of the index patient did not reveal respiratory abnormalities. Nerve conduction studies were normal in the three patients. [kundoc.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]

• 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]

• Neck Muscle Weakness

  Neck muscle weakness MedGen UID: 66808 •Concept ID: C0240479 • Finding Decreased strength of the neck musculature. [ncbi.nlm.nih.gov]

• Muscle Weakness Congenital

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

• 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

  On the one hand, patients of the same type shared a number of clinical features: limb weakness and delayed motor milestone at birth in the typical congenital, proximal limb weakness at early childhood in the mild childhood and rapidly progressive disease [spandidos-publications.com]

  Of note, most carriers are asymptomatic, but mild facial and limb weakness may be present. Progression may result in gait difficulty and kyphoscoliosis. [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

  Gowers sign MedGen UID: 65865 •Concept ID: C0234182 • Finding A phenomenon whereby patients are not able to stand up without the use of the hands owing to weakness of the proximal muscles of the lower limbs. [ncbi.nlm.nih.gov]

  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

  Limb muscle weakness MedGen UID: 107956 •Concept ID: C0587246 • Finding Hyporeflexia MedGen UID: 195967 •Concept ID: C0700078 • Finding Reduction of neurologic reflexes such as the knee-jerk reaction. [ncbi.nlm.nih.gov]

  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]

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]

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

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]

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]

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]

18:230) Cardiac and extraocular muscles are typically spared Pathophysiology Congenital forms caused by mutations involving the thin filament of the sarcomere and cause contractile dysfunction, leading to muscle weakness (J Neuromuscul Dis 2017;4:99) Etiology [pathologyoutlines.com]

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

[…] 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]

[…] and 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 Epidemiology [pathologyoutlines.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]

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]

Complications Congenital myopathies are associated with a number of complications, such as: Delays in motor skills Scoliosis Pneumonia Respiratory failure Feeding problems Prevention There's no way to prevent congenital myopathies. [mayoclinic.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]