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Desmin-related myofibrillar myopathy(MFM1)

MedGen UID:
330449
Concept ID:
C1832370
Disease or Syndrome
Synonyms: Desmin related myopathy (former name); Desmin storage myopathy (former name); DESMIN-RELATED MYOPATHY WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY; Desminopathy; MFM1; Myofibrillar myopathy 1; MYOFIBRILLAR MYOPATHY WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY
SNOMED CT: Desminopathy (770627003); Desmin-related myofibrillar myopathy (770627003)
 
Gene (location): DES (2q35)
 
Monarch Initiative: MONDO:0011076
OMIM®: 601419
Orphanet: ORPHA98909

Definition

Myofibrillar myopathy (MFM) is a noncommittal term that refers to a group of morphologically homogeneous, but genetically heterogeneous chronic neuromuscular disorders. The morphologic changes in skeletal muscle in MFM result from disintegration of the sarcomeric Z disc and the myofibrils, followed by abnormal ectopic accumulation of multiple proteins involved in the structure of the Z disc, including desmin, alpha-B-crystallin (CRYAB; 123590), dystrophin (300377), and myotilin (TTID; 604103). Genetic Heterogeneity of Myofibrillar Myopathy See also MFM2A (608810) and MFM2B (613869), both caused by mutation in the CRYAB gene (123590); MFM3 (609200), caused by mutation in the MYOT gene (604103); MFM4 (609452), caused by mutation in the ZASP gene (LDB3; 605906); MFM5 (609524), caused by mutation in the FLNC gene (102565); MFM6 (612954), caused by mutation in the BAG3 gene (603883); MFM7 (617114), caused by mutation in the KY gene (605739); MFM8 (617258), caused by mutation in the PYROXD1 gene (617220); MFM9 (603689), caused by mutation in the TTN gene (188840); MFM10 (619040), caused by mutation in the SVIL UNC45B gene (611220); MFM11 (619178), caused by mutation in the UNC45B gene (611220); MFM12 (619424), caused by mutation in the MYL2 gene (160781); and MFM13 (621078), caused by mutation in the HSPB8 gene (608014). 'Desmin-related myopathy' is another term referring to MFM in which there are intrasarcoplasmic aggregates of desmin, usually in addition to other sarcomeric proteins. Rigid spine syndrome (602771), caused by mutation in the SEPN1 gene (606210), is another desmin-related myopathy. Goebel (1995) provided a review of desmin-related myopathy. [from OMIM]

Additional description

From MedlinePlus Genetics
Myofibrillar myopathy refers to a group of disorders that are characterized by muscle weakness (myopathy) that worsens over time. Myofibrillar myopathy primarily affects the skeletal muscles, which are the muscles that the body uses for movement. In some cases, the heart (cardiac) muscle is also affected.

The signs and symptoms of myofibrillar myopathy vary widely among affected individuals. People with this disorder typically begin to develop myopathy in mid-adulthood. However, the features of this condition can appear anytime between infancy and late adulthood. Myopathy most often begins in the hands, forearms, feet, and lower legs (distal muscles), but some people first experience weakness in the muscles near the center of the body (proximal muscles). The weakness can spread to other muscles. 

Other signs and symptoms of myofibrillar myopathy can include muscle pain (myalgia) or weakness and loss of sensation in the limbs (peripheral neuropathy). Affected individuals may also have skeletal problems, which can include joint stiffness (contractures) and abnormal side-to-side curvature of the spine (scoliosis). Some people with myofibrillar myopathy develop clouding in the lenses of the eyes (cataracts).

Some people with myofibrillar myopathy develop cardiomyopathy, which is a weakening of the heart muscle. In some cases, cardiomyopathy is the first sign of the disorder.

In rare cases, the muscles used for speaking, swallowing, or breathing are affected in people with myofibrillar myopathy. When the muscles used for breathing are involved, affected individuals may experience extreme tiredness (fatigue), breathing difficulties, and, in severe cases, respiratory failure.   https://medlineplus.gov/genetics/condition/myofibrillar-myopathy

Clinical features

From HPO
Hyporeflexia of lower limbs
MedGen UID:
371881
Concept ID:
C1834696
Finding
Reduced intensity of muscle tendon reflexes in the lower limbs. Reflexes are elicited by stretching the tendon of a muscle, e.g., by tapping.
Primary dilated cardiomyopathy
MedGen UID:
2880
Concept ID:
C0007193
Disease or Syndrome
Dilated cardiomyopathy is a form of heart disease in which the heart (cardiac) muscle becomes thin and enlarged (dilated). The dilation, which typically starts in the lower left chamber of the heart (left ventricle), makes it harder for the heart to pump blood to the rest of the body. \n\nDilated cardiomyopathy is called nonsyndromic dilated cardiomyopathy when it cannot be explained by other causes, such as a heart attack or damage to the valves of the heart, and is not associated with signs and symptoms that affect other parts of the body.  \n\nThe signs and symptoms of nonsyndromic dilated cardiomyopathy vary among affected individuals, even among members of the same family. The signs and symptoms typically begin in mid-adulthood, but they can occur at any time from infancy to late adulthood. Affected individuals may have a sensation of fluttering or pounding in the chest (palpitations); shortness of breath, especially when lying down or during physical activity; fatigue; and swelling of the legs and feet. Affected individuals may also have episodes of dizziness or fainting (syncope). \n\nOver time, people with nonsyndromic dilated cardiomyopathy may develop life-threatening complications, which can include abnormal heart rhythms (arrhythmias) and heart failure. Although uncommon, sudden death can occur in people with nonsyndromic dilated cardiomyopathy, even if they have no other symptoms of the condition.\n\n
Hypertrophic cardiomyopathy
MedGen UID:
2881
Concept ID:
C0007194
Disease or Syndrome
Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.
Restrictive cardiomyopathy
MedGen UID:
40111
Concept ID:
C0007196
Disease or Syndrome
Restrictive left ventricular physiology is characterized by a pattern of ventricular filling in which increased stiffness of the myocardium causes ventricular pressure to rise precipitously with only small increases in volume, defined as restrictive ventricular physiology in the presence of normal or reduced diastolic volumes (of one or both ventricles), normal or reduced systolic volumes, and normal ventricular wall thickness.
Third degree atrioventricular block
MedGen UID:
56230
Concept ID:
C0151517
Disease or Syndrome
Third-degree atrioventricular (AV) block (also referred to as complete heart block) is the complete dissociation of the atria and the ventricles. Third-degree AV block exists when more P waves than QRS complexes exist and no relationship (no conduction) exists between them.
Bradycardia
MedGen UID:
140901
Concept ID:
C0428977
Finding
A slower than normal heart rate (in adults, slower than 60 beats per minute).
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
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.
Neck muscle weakness
MedGen UID:
66808
Concept ID:
C0240479
Finding
Decreased strength of the neck musculature.
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.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
EMG: myopathic abnormalities
MedGen UID:
867362
Concept ID:
C4021726
Pathologic Function
The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials.
Late-onset proximal muscle weakness
MedGen UID:
871110
Concept ID:
C4025578
Finding
Lack of strength of the proximal musculature occurring late in the clinical course.
Respiratory insufficiency due to muscle weakness
MedGen UID:
812797
Concept ID:
C3806467
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Desmin-related myofibrillar myopathy in Orphanet.

Professional guidelines

Recent clinical studies

Etiology

Taylor MR, Slavov D, Ku L, Di Lenarda A, Sinagra G, Carniel E, Haubold K, Boucek MM, Ferguson D, Graw SL, Zhu X, Cavanaugh J, Sucharov CC, Long CS, Bristow MR, Lavori P, Mestroni L; Familial Cardiomyopathy Registry; BEST (Beta-Blocker Evaluation of Survival Trial) DNA Bank
Circulation 2007 Mar 13;115(10):1244-51. Epub 2007 Feb 26 doi: 10.1161/CIRCULATIONAHA.106.646778. PMID: 17325244

Diagnosis

Vlaeminck J, Uyttebroeck S, De Schutter E, Cordenier A, Wellekens S, Ströker E, De Rooms K, Helsen C, Hes FJ, Giron P
Front Genet 2025;16:1597851. Epub 2025 Jun 18 doi: 10.3389/fgene.2025.1597851. PMID: 40606663Free PMC Article
Taylor MR, Slavov D, Ku L, Di Lenarda A, Sinagra G, Carniel E, Haubold K, Boucek MM, Ferguson D, Graw SL, Zhu X, Cavanaugh J, Sucharov CC, Long CS, Bristow MR, Lavori P, Mestroni L; Familial Cardiomyopathy Registry; BEST (Beta-Blocker Evaluation of Survival Trial) DNA Bank
Circulation 2007 Mar 13;115(10):1244-51. Epub 2007 Feb 26 doi: 10.1161/CIRCULATIONAHA.106.646778. PMID: 17325244

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