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Autosomal dominant limb-girdle muscular dystrophy type 1F(LGMD1F; LGMDD2)

MedGen UID:
333983
Concept ID:
C1842062
Disease or Syndrome
Synonyms: Limb-girdle muscular dystrophy, type 1F; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL DOMINANT 2
Modes of inheritance:
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.
 
Gene (location): TNPO3 (7q32.1)
 
Monarch Initiative: MONDO:0012034
OMIM®: 608423
Orphanet: ORPHA55595

Definition

Autosomal dominant limb-girdle muscular dystrophy-2 is a myopathy characterized by proximal muscle weakness primarily affecting the lower limbs, but also affecting the upper limbs in most patients. Affected individuals also have distal muscle weakness of the hands and lower leg muscles. There is variability in presentation and progression. Some patients present in early childhood with mildly delayed walking and difficulty running and jumping, whereas others present as adults with mainly pelvic-girdle weakness. Patients with early onset tend to have a more severe disorder, and may develop contractures, loss of independent ambulation, and respiratory insufficiency. Muscle biopsy shows dystrophic changes with abnormal nuclei, rimmed vacuoles, and filamentous inclusions (summary by Melia et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of autosomal dominant limb-girdle muscular dystrophy, see LGMDD1 (603511). [from OMIM]

Clinical features

From HPO
Scapular winging
MedGen UID:
66822
Concept ID:
C0240953
Anatomical Abnormality
Abnormal protrusion of the scapula away from the surface of the back.
Shoulder girdle muscle weakness
MedGen UID:
96533
Concept ID:
C0427063
Finding
The shoulder, or pectoral, girdle is composed of the clavicles and the scapulae. Shoulder-girdle weakness refers to lack of strength of the muscles attaching to these bones, that is, lack of strength of the muscles around the shoulders.
Pelvic girdle muscle weakness
MedGen UID:
96534
Concept ID:
C0427064
Finding
Weakness of the muscles of the pelvic girdle (also known as the hip girdle), that is, lack of strength of the muscles around the pelvis.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Muscular dystrophy
MedGen UID:
44527
Concept ID:
C0026850
Disease or Syndrome
The term dystrophy means abnormal growth. However, muscular dystrophy is used to describe primary myopathies with a genetic basis and a progressive course characterized by progressive skeletal muscle weakness and wasting, defects in muscle proteins, and histological features of muscle fiber degeneration (necrosis) and regeneration. If possible, it is preferred to use other HPO terms to describe the precise phenotypic abnormalities.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Autophagic vacuoles
MedGen UID:
107466
Concept ID:
C0544966
Finding
The lysosomal-vacuolar pathway has a role in the controlled intracellular digestion of macromolecules such as protein complexes and organelles. This feature refers to the presence of an abnormally increased number of autophagic vacuoles in muscle tissue.
Difficulty running
MedGen UID:
108251
Concept ID:
C0560346
Finding
Reduced ability to run.
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).
Rimmed vacuoles
MedGen UID:
340089
Concept ID:
C1853932
Finding
Presence of abnormal vacuoles (membrane-bound organelles) in the sarcolemma. On histological staining with hematoxylin and eosin, rimmed vacuoles are popcorn-like clear vacuoles with a densely blue rim. The vacuoles are often associated with cytoplasmic and occasionally intranuclear eosinophilic inclusions.
Spinal rigidity
MedGen UID:
346721
Concept ID:
C1858025
Finding
Reduced ability to move the vertebral column with a resulting limitation of neck and trunk flexion.
Increased connective tissue
MedGen UID:
400898
Concept ID:
C1866021
Finding
The presence of an abnormally increased amount of connective tissue.
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 distal muscle weakness
MedGen UID:
871100
Concept ID:
C4025565
Finding
Respiratory insufficiency due to muscle weakness
MedGen UID:
812797
Concept ID:
C3806467
Finding
Abnormality of metabolism/homeostasis
MedGen UID:
867398
Concept ID:
C4021768
Finding
Pallor
MedGen UID:
10547
Concept ID:
C0030232
Finding
Abnormally pale skin.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Autosomal dominant limb-girdle muscular dystrophy type 1F in Orphanet.

Recent clinical studies

Etiology

Pál E, Zima J, Hadzsiev K, Ito YA, Hartley T; Care4Rare Canada Consortium., Boycott KM, Melegh B
Eur J Med Genet 2019 Jul;62(7):103662. Epub 2019 May 6 doi: 10.1016/j.ejmg.2019.05.001. PMID: 31071488

Diagnosis

Melià MJ, Kubota A, Ortolano S, Vílchez JJ, Gámez J, Tanji K, Bonilla E, Palenzuela L, Fernández-Cadenas I, Pristoupilová A, García-Arumí E, Andreu AL, Navarro C, Hirano M, Martí R
Brain 2013 May;136(Pt 5):1508-17. Epub 2013 Mar 29 doi: 10.1093/brain/awt074. PMID: 23543484Free PMC Article

Prognosis

Peterle E, Fanin M, Semplicini C, Padilla JJ, Nigro V, Angelini C
J Neurol 2013 Aug;260(8):2033-41. Epub 2013 Apr 30 doi: 10.1007/s00415-013-6931-1. PMID: 23632945
Melià MJ, Kubota A, Ortolano S, Vílchez JJ, Gámez J, Tanji K, Bonilla E, Palenzuela L, Fernández-Cadenas I, Pristoupilová A, García-Arumí E, Andreu AL, Navarro C, Hirano M, Martí R
Brain 2013 May;136(Pt 5):1508-17. Epub 2013 Mar 29 doi: 10.1093/brain/awt074. PMID: 23543484Free PMC Article

Clinical prediction guides

Melià MJ, Kubota A, Ortolano S, Vílchez JJ, Gámez J, Tanji K, Bonilla E, Palenzuela L, Fernández-Cadenas I, Pristoupilová A, García-Arumí E, Andreu AL, Navarro C, Hirano M, Martí R
Brain 2013 May;136(Pt 5):1508-17. Epub 2013 Mar 29 doi: 10.1093/brain/awt074. PMID: 23543484Free PMC Article

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