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]

Results: All patients, two males and one female, presented a consistent clinical phenotype characterized by neonatal hypotonia, retarded motor development and bone deformities including pectus excavatum, elongated face and high-arched palate. [neurology.org]

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]

A less common presentation of CNM occurs with autosomal dominant or recessive inheritance, presenting with mild weakness and hypotonia, which may be unrecognizable in infants. [rarediseases.org]

• Feeding Difficulties

  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]

  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]

  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]

  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]

• Developmental Delay

  BETA-UREIDOPROPIONASE DEFICIENCY; UPB1D Is also known as ;beta-alanine synthase deficiency Related symptoms: Autosomal recessive inheritance Intellectual disability Seizures Global developmental delay Generalized hypotonia SOURCES: MONDO ORPHANET UMLS [mendelian.co]

  Delay Developmental Delay associated with Autism, Autism Spectrum Disorder and Aspergers Syndrome Down Syndrome/Trisomy 21 Dravet Syndrome Edwards Syndrome/Trisomy 18 Fragile X Syndrome Fumarase Deficiency GLUT1-DS Condition Glutaric Aciduria Type 1 [bladderbowel.gov.au]

  Myopathies are grouped as follows: Congenital myopathies: characterized by developmental delays in motor skills, skeletal and facial abnormalities. They are occasionally diagnosed at birth. [thefetus.net]

  Motor delay MedGen UID: 381392 •Concept ID: C1854301 • Finding A type of Developmental delay characterized by a delay in acquiring motor skills. [ncbi.nlm.nih.gov]

  He shows sandal gaps on both flat feet with clinodactyly of the fourth and fifth toes (and more) 612513 PMID: 22579565 severe developmental delay, congenital microcephaly, intractable epilepsy, and renal anomalies, as well as a congenital choledochal [panelapp.genomicsengland.co.uk]

• Difficulty Walking

  Difficulty walking MedGen UID: 86319 •Concept ID: C0311394 • Finding Reduced ability to walk (ambulate). [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]

• Swelling

  Without treatment, 50% of patients develop joint pain and swelling of the bones surrounding the large joints, especially the knees. There can be growth delay; children with NOMID are often very short. Not all children have all of these symptoms. [rheumatology.org]

• Respiratory Insufficiency

  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]

  Nemaline Myopathy is a condition characterized by proximal muscle weakness, delayed motor milestones and occasionally respiratory insufficiency and feeding problems (Sewry, Laitila, and Wallgren-Pettersson 2019). [childrenshospital.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]

  Recently, human leiomodin-3 (Lmod3) mutations were found to cause nemaline myopathy with shorter thin filaments and impaired contractility, leading to severe muscle weakness and respiratory insufficiency. [scripps.edu]

• Respiratory Distress

  distress and dysphagia - (AR) 3.32 Multiple EGF-like-domains 10 * Recessive congenital myopathy with minicores * Early onset myopathy, areflexia, respiratory distress and dysphagia - EMARDD Recessive congenital myopathy with minicores - (AR) 3.33 Multiple [musclegenetable.fr]

  distress Acidosis EEG abnormality Hypertrophic cardiomyopathy Lactic acidosis Full cheeks Polyneuropathy Increased serum lactate Neuronal loss in central nervous system Epileptic encephalopathy Bradycardia Neonatal respiratory distress Motor polyneuropathy [mendelian.co]

  distress, and dysphagia, early-onset, 614399 MEGF10 Myopathy, areflexia, respiratory distress, and dysphagia, early-onset, mild variant, 614399 DNM2 Myopathy, centronuclear, 160150 MYF6 Myopathy, centronuclear, 3, 614408 CCDC78 Myopathy, centronuclear [gsdseq.ir]

  distress, and dysphagia MTM1 ✓ X-linked centronuclear myopathy MYF6 * ✓ centronuclear myopathy-3 MYH7 ✓ ✓ myosin storage myopathy, Laing distal myopathy, congenital fiber-type disproportion MYPN ✓ nemaline myopathy NEB ✓ nemaline myopathy-2 RYR1 ✓ ✓ [invitae.com]

  Distress, andDysphagia Myopathy, areflexia, respiratory distress, and dysphagia, early-onset, 614399 Tags Green List (high evidence) MICU1 2 reviews 2 green BIALLELIC, autosomal or pseudoautosomal Sources Expert Review Green Radboud University Medical [panelapp.genomicsengland.co.uk]

• Dyspnea

  Shortness of breath (dyspnea). As people with NM get older, symptoms may include: Abnormal spine rigidity. Scoliosis. Shortening or tightening of your joints (joint contractures). Sunken chest (pectus excavatum). [my.clevelandclinic.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]

• Dysphagia

  DEVELOPMENT: All the children presented dysphagia, with severe feeding problems during the first three years of life that nevertheless are somewhat mitigated as time goes by. [ncbi.nlm.nih.gov]

  (AR) 3.32 Multiple EGF-like-domains 10 * Recessive congenital myopathy with minicores * Early onset myopathy, areflexia, respiratory distress and dysphagia - EMARDD Recessive congenital myopathy with minicores - (AR) 3.33 Multiple EGF-like-domains [musclegenetable.fr]

  In more serious cases there is dysphagia and severe respiratory problems (rarely and cardiomyopathy). Ophthalmoplegia also occurs in 20% of cases. [mdahellas.gr]

  early-onset, 614399 MEGF10 Myopathy, areflexia, respiratory distress, and dysphagia, early-onset, mild variant, 614399 DNM2 Myopathy, centronuclear, 160150 MYF6 Myopathy, centronuclear, 3, 614408 CCDC78 Myopathy, centronuclear, 4, 614807 BIN1 Myopathy [gsdseq.ir]

  Dysphagia, cardiomyopathy and ophtalmoplegia were not observed. [scielo.br]

• Proximal Muscle Weakness

  Most affected patients develop hypotonia and mild proximal muscle weakness as neonates, but sometimes symptoms of core myopathy do not manifest until adulthood. Many also have facial weakness. [msdmanuals.com]

  Major clinical symptoms for NEM include the following 1 : Muscle weakness of face, neck and trunk and upper arms and legs (proximal muscle weakness) Hypotonia Decreased or absent deep tendon reflexes Feeding and swallowing difficulties Breathing difficulties [centogene.com]

  Nemaline Myopathy is a condition characterized by proximal muscle weakness, delayed motor milestones and occasionally respiratory insufficiency and feeding problems (Sewry, Laitila, and Wallgren-Pettersson 2019). [childrenshospital.org]

• Foot Deformity

  Affected individuals may have feeding and swallowing difficulties, foot deformities, abnormal curvature of the spine (scoliosis), and joint deformities (contractures). [encyclopedia.pub]

  Other symptoms include foot deformities, curvature of the spine (scoliosis), as well as joint deformities (contractures). (For more information, search for “nemaline myopathy” in the Rare Disease Database.) [rarediseases.org]

• Joint Deformity

  Other treatments include physical therapy, splints and other aids to treat joint deformities if they occur. Surgery is occasionally needed. Hearing aids are needed for children with deafness. [rheumatology.org]

  Affected individuals may have feeding and swallowing difficulties, foot deformities, abnormal curvature of the spine (scoliosis), and joint deformities (contractures). [encyclopedia.pub]

  At least three mutations in the TPM2 gene have been found to cause distal arthrogryposis type 1, a disorder characterized by joint deformities (contractures) in the hands and feet. [ghr.nlm.nih.gov]

• Lordosis

  Some affected individuals develop an abnormally curved lower back ( lordosis ) or a spine that curves to the side ( scoliosis ). [ghr.nlm.nih.gov]

  Drooping eyelids High-arched palate Swallowing difficulties Delay in reaching developmental milestones, such as sitting, crawling, walking or running Lordosis, scoliosis Breathing difficulties Tiring easily with mild exertion How is Cap Myopathy Diagnosed [dovemed.com]

  Some affected individuals develop an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). [medlineplus.gov]

  In addition, there is difficulty in swallowing, feeding from the neonatal age, in movement, difficulty breathing, bleeding, delayed development and skills, large curve of hard palate, characteristic long face and scoliosis / lordosis may also develop. [mdahellas.gr]

  If the muscles extending the hip joint are affected, the posture in that joint becomes flexed and lumbar lordosis increases. The patients usually have difficulties standing up from a sitting position. [ncbi.nlm.nih.gov]

• 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]

  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]

• Foot Drop

  His first symptom was foot drop at the age of three, followed by distal muscle atrophy, slight hypomimia, high-arched palate, and weakness of the neck and elbow flexors, hands, tibialis anterior and toe extensors. [researchportal.helsinki.fi]

  Myopathies (Muscular Dystrophy Association) - PDF Also in Spanish Myopathy (National Institute of Neurological Disorders and Stroke) Foot Drop (National Institute of Neurological Disorders and Stroke) [medlineplus.gov]

  Bilateral foot-drop as predominant symptom in nebulin (NEB) gene related "core-rod" congenital myopathy Malfatti E ; Monges S ; Lehtokari VL ; Schaeffer U ; Abath Neto O ; Kiiski K ; Lubieniecki F ; Taratuto AL ; Wallgren-Pettersson C ; Laporte J ; Romero [myobase.org]

  Childhood-onset nemaline myopathy This condition may lead to inability to bend your foot up toward your leg (foot drop). It can progress to inability to move your ankles and lower leg muscles. [my.clevelandclinic.org]

• 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]

  From birth, these patients had marked ptosis, facial weakness, poor sucking, hypotonia, respiratory weakness, and relatively preserved limb strength. [emedicine.medscape.com]

  Facial weakness, ophthalmoparesis, ptosis, dysphagia and limb contractures are less common features of cap myopathy and have thus far only been reported in patients with TPM2 mutations (Table 1). 3. [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]

  Status epilepticus Bifid scrotum Delayed CNS myelination Bladder exstrophy Exstrophy Pes planus Lower limb muscle weakness Mitral valve prolapse Anal atresia Lumbar hyperlordosis Frequent falls Reduced tendon reflexes Nasal speech Poor head control Gowers [mendelian.co]

  Fifty percent of individuals in the study were unable to rise from the floor; 16% could rise with assistance; 16% had a classic Gowers sign; 14% had a modified Gowers sign; and only 7% rose without difficulty (n = 44 total) (figure 3B). [n.neurology.org]

  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

  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]

• Delayed Milestone

  DMD usually presents in early childhood with delayed milestones, including delays in sitting and standing independently. [blueprintgenetics.com]

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]

Is there a treatment? There is currently no effective treatment to halt the progression of the nemaline myopathies, but management of the condition is very important for prolonging life. [musculardystrophyuk.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]

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

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]

(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]

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]

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]

[…] 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]

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]

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

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]

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]

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]

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