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Congenital myopathy with fiber type disproportion(CFTD; CFTDM; NEM1; CMYP4A; CAPM1, FOR...)

MedGen UID:
108177
Concept ID:
C0546264
Disease or Syndrome
Synonyms: Congenital Fiber-Type Disproportion; Congenital fiber-type disproportion myopathy
SNOMED CT: Congenital myopathy with fiber type disproportion (240084007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Genes (locations): ACTA1 (1q42.13); MYH7 (14q11.2); RYR1 (19q13.2); SELENON (1p36.11); TPM2 (9p13.3); TPM3 (1q21.3)
 
Monarch Initiative: MONDO:0009711
OMIM®: 191030; 255310
Orphanet: ORPHA2020

Definition

Congenital fiber-type disproportion is a condition that primarily affects skeletal muscles, which are muscles used for movement. People with this condition typically experience muscle weakness (myopathy), particularly in the muscles of the shoulders, upper arms, hips, and thighs. Weakness can also affect the muscles of the face and muscles that control eye movement (ophthalmoplegia), sometimes causing droopy eyelids (ptosis). Individuals with congenital fiber-type disproportion generally have a long face, a high arch in the roof of the mouth (high-arched palate), and crowded teeth.

Individuals with congenital fiber-type disproportion may have joint deformities (contractures) and an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Approximately 30 percent of people with this disorder experience mild to severe breathing problems related to weakness of muscles needed for breathing. Some people who experience these breathing problems require use of a machine to help regulate their breathing at night (noninvasive mechanical ventilation), and occasionally during the day as well. About 30 percent of affected individuals have difficulty swallowing due to muscle weakness in the throat. Rarely, people with this condition have a weakened and enlarged heart muscle (dilated cardiomyopathy).

The severity of congenital fiber-type disproportion varies widely. It is estimated that up to 25 percent of affected individuals experience severe muscle weakness at birth and die in infancy or childhood. Others have only mild muscle weakness that becomes apparent in adulthood. Most often, the signs and symptoms of this condition appear by age 1. The first signs of this condition are usually decreased muscle tone (hypotonia) and muscle weakness. In most cases, muscle weakness does not worsen over time, and in some instances it may improve. Although motor skills such as standing and walking may be delayed, many affected children eventually learn to walk. These individuals often have less stamina than their peers, but they remain active. Rarely, people with this condition have a progressive decline in muscle strength over time. These individuals may lose the ability to walk and require wheelchair assistance. [from MedlinePlus Genetics]

Clinical features

From HPO
Primary dilated cardiomyopathy
MedGen UID:
2880
Concept ID:
C0007193
Disease or Syndrome
Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.\n\nIt usually takes many years for symptoms of familial dilated cardiomyopathy to cause health problems. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Bulbar palsy
MedGen UID:
898626
Concept ID:
C4082299
Disease or Syndrome
Bulbar weakness (or bulbar palsy) refers to bilateral impairment of function of the lower cranial nerves IX, X, XI and XII, which occurs due to lower motor neuron lesion either at nuclear or fascicular level in the medulla or from bilateral lesions of the lower cranial nerves outside the brain-stem. Bulbar weakness is often associated with difficulty in chewing, weakness of the facial muscles, dysarthria, palatal weakness and regurgitation of fluids, dysphagia, and dysphonia.
Congenital hip dislocation
MedGen UID:
9258
Concept ID:
C0019555
Disease or Syndrome
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Facial palsy
MedGen UID:
87660
Concept ID:
C0376175
Disease or Syndrome
Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form.
Generalized muscle weakness
MedGen UID:
155433
Concept ID:
C0746674
Sign or Symptom
Generalized weakness or decreased strength of the muscles, affecting both distal and proximal musculature.
Lumbar hyperlordosis
MedGen UID:
263149
Concept ID:
C1184923
Finding
An abnormal accentuation of the inward curvature of the spine in the lumbar region.
Centrally nucleated skeletal muscle fibers
MedGen UID:
330782
Concept ID:
C1842170
Finding
An abnormality in which the nuclei of sarcomeres take on an abnormally central localization (or in which this feature is found in an increased proportion of muscle cells).
Limb joint contracture
MedGen UID:
369611
Concept ID:
C1969879
Anatomical Abnormality
A contracture (chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin) that prevent normal movement of one or more joints of the limbs.
Neonatal hypotonia
MedGen UID:
412209
Concept ID:
C2267233
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Type 1 fibers relatively smaller than type 2 fibers
MedGen UID:
871106
Concept ID:
C4025571
Finding
The presence of abnormal muscle fiber size such that type 1 fibers are smaller than type 2 fibers.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Reduced forced vital capacity
MedGen UID:
337630
Concept ID:
C1846678
Finding
An abnormal reduction in the amount of air a person can expel following maximal inspiration.
Respiratory insufficiency due to muscle weakness
MedGen UID:
812797
Concept ID:
C3806467
Finding
Weak cry
MedGen UID:
65892
Concept ID:
C0234860
Finding
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Long face
MedGen UID:
324419
Concept ID:
C1836047
Finding
Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).
Narrow face
MedGen UID:
373334
Concept ID:
C1837463
Finding
Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective).
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Ophthalmoplegia
MedGen UID:
45205
Concept ID:
C0029089
Sign or Symptom
Paralysis of one or more extraocular muscles that are responsible for eye movements.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCongenital myopathy with fiber type disproportion
Follow this link to review classifications for Congenital myopathy with fiber type disproportion in Orphanet.

Professional guidelines

PubMed

Gómez-Oca R, Cowling BS, Laporte J
Int J Mol Sci 2021 Oct 21;22(21) doi: 10.3390/ijms222111377. PMID: 34768808Free PMC Article
Natera-de Benito D, Ortez C, Jou C, Jimenez-Mallebrera C, Codina A, Carrera-García L, Expósito-Escudero J, Cesar S, Martorell L, Gallano P, Gonzalez-Quereda L, Cuadras D, Colomer J, Yubero D, Palau F, Nascimento A
Pediatr Neurol 2021 Feb;115:50-65. Epub 2020 Nov 5 doi: 10.1016/j.pediatrneurol.2020.11.002. PMID: 33333461
Morin G, Biancalana V, Echaniz-Laguna A, Noury JB, Lornage X, Moggio M, Ripolone M, Violano R, Marcorelles P, Maréchal D, Renaud F, Maurage CA, Tard C, Cuisset JM, Laporte J, Böhm J
Hum Mutat 2020 Jan;41(1):17-37. Epub 2019 Sep 15 doi: 10.1002/humu.23899. PMID: 31448844

Recent clinical studies

Etiology

Li N, Zhao Z, Shen H, Bing Q, Guo X, Hu J
Neurol Sci 2018 Feb;39(2):333-339. Epub 2017 Nov 24 doi: 10.1007/s10072-017-3192-2. PMID: 29170849

Diagnosis

Li N, Zhao Z, Shen H, Bing Q, Guo X, Hu J
Neurol Sci 2018 Feb;39(2):333-339. Epub 2017 Nov 24 doi: 10.1007/s10072-017-3192-2. PMID: 29170849
Iwai K, Yoshida Y, Kazuta T, Suzuki T, Kuki I
Pediatr Int 2017 Sep;59(9):1025-1027. Epub 2017 Aug 7 doi: 10.1111/ped.13339. PMID: 28786238
Na SJ, Kim WK, Kim TS, Kang SW, Lee EY, Choi YC
Yonsei Med J 2006 Aug 31;47(4):513-8. doi: 10.3349/ymj.2006.47.4.513. PMID: 16941741Free PMC Article

Prognosis

Ben Yaou R, Navarro C, Quijano-Roy S, Bertrand AT, Massart C, De Sandre-Giovannoli A, Cadiñanos J, Mamchaoui K, Butler-Browne G, Estournet B, Richard P, Barois A, Lévy N, Bonne G
Eur J Hum Genet 2011 Jun;19(6):647-54. Epub 2011 Jan 26 doi: 10.1038/ejhg.2010.256. PMID: 21267004Free PMC Article
Na SJ, Kim WK, Kim TS, Kang SW, Lee EY, Choi YC
Yonsei Med J 2006 Aug 31;47(4):513-8. doi: 10.3349/ymj.2006.47.4.513. PMID: 16941741Free PMC Article

Clinical prediction guides

Ben Yaou R, Navarro C, Quijano-Roy S, Bertrand AT, Massart C, De Sandre-Giovannoli A, Cadiñanos J, Mamchaoui K, Butler-Browne G, Estournet B, Richard P, Barois A, Lévy N, Bonne G
Eur J Hum Genet 2011 Jun;19(6):647-54. Epub 2011 Jan 26 doi: 10.1038/ejhg.2010.256. PMID: 21267004Free PMC Article
Na SJ, Kim WK, Kim TS, Kang SW, Lee EY, Choi YC
Yonsei Med J 2006 Aug 31;47(4):513-8. doi: 10.3349/ymj.2006.47.4.513. PMID: 16941741Free PMC Article

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