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Autosomal recessive limb-girdle muscular dystrophy type 2K(LGMD2K; MDDGC1; LGMDR11)

MedGen UID:
332193
Concept ID:
C1836373
Disease or Syndrome
Synonyms: Limb-girdle muscular dystrophy-dystroglycanopathy, type C1; MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2K; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 1
SNOMED CT: Autosomal recessive limb girdle muscular dystrophy type 2K (720523006); Limb girdle muscular dystrophy with intellectual disability syndrome (720523006)
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).
 
Gene (location): POMT1 (9q34.13)
 
Monarch Initiative: MONDO:0012248
OMIM®: 609308
Orphanet: ORPHA86812

Definition

Limb-girdle muscular dystrophies resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239) represent the mildest end of the phenotypic spectrum of muscular dystrophies collectively known as dystroglycanopathies. The limb-girdle phenotype is characterized by onset of muscular weakness apparent after ambulation is achieved; mental retardation and mild brain anomalies are variable (Balci et al., 2005; review by Godfrey et al., 2007). The most severe end of the phenotypic spectrum of dystroglycanopathies is represented by congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A; see MDDGA1, 236670), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), and the intermediate range of the spectrum is represented by congenital muscular dystrophy-dystroglycanopathy with or without mental retardation (type B; see MDDGB1, 613155). Genetic Heterogeneity of Limb-Girdle Muscular Dystrophy-Dystroglycanopathy (Type C) Limb-girdle muscular dystrophy due to defective glycosylation of DAG1 is genetically heterogeneous. See also MDDGC2 (613158), caused by mutation in the POMT2 gene (607439); MDDGC3 (613157), caused by mutation in the POMGNT1 gene (606822); MDDGC4 (611588), caused by mutation in the FKTN gene (607440); MDDGC5 (607155), caused by mutation in the FKRP gene (606596); MDDGC7 (616052), caused by mutation in the ISPD gene (CRPPA; 614631); MDDGC8 (618135), caused by mutation in the POMGNT2 gene (614828); MDDGC9 (613818) caused by mutation in the DAG1 gene (128239); MDDGC12 (616094), caused by mutation in the POMK gene (615247); MDDGC14 (615352) caused by mutation in the GMPPB gene (615320); and MDDGC15 (612937), caused by mutation in the DPM3 gene (605951). [from OMIM]

Clinical features

From HPO
Limb-girdle muscle weakness
MedGen UID:
347625
Concept ID:
C1858127
Finding
Weakness of the limb-girdle muscles (also known as the pelvic and shoulder girdles), that is, lack of strength of the muscles around the shoulders and the pelvis.
Cardiomyopathy
MedGen UID:
209232
Concept ID:
C0878544
Disease or Syndrome
A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.
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.
Easy fatigability
MedGen UID:
373253
Concept ID:
C1837098
Finding
Increased susceptibility to fatigue.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
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.
Joint stiffness
MedGen UID:
56403
Concept ID:
C0162298
Sign or Symptom
Joint stiffness is a perceived sensation of tightness in a joint or joints when attempting to move them after a period of inactivity. Joint stiffness typically subsides over time.
Difficulty climbing stairs
MedGen UID:
68676
Concept ID:
C0239067
Finding
Reduced ability to climb stairs.
Difficulty walking
MedGen UID:
86319
Concept ID:
C0311394
Finding
Reduced ability to walk (ambulate).
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.
Lumbar hyperlordosis
MedGen UID:
263149
Concept ID:
C1184923
Finding
An abnormal accentuation of the inward curvature of the spine in the lumbar region.
Calf muscle hypertrophy
MedGen UID:
335868
Concept ID:
C1843057
Finding
Muscle hypertrophy affecting the calf muscles.
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.
Hypoglycosylation of alpha-dystroglycan
MedGen UID:
863535
Concept ID:
C4015098
Finding
A reduction in the degree of glycosylation of alpha-dystroglycan in muscle tissue.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAutosomal recessive limb-girdle muscular dystrophy type 2K
Follow this link to review classifications for Autosomal recessive limb-girdle muscular dystrophy type 2K in Orphanet.

Professional guidelines

PubMed

Ko YJ, Cho A, Kim WJ, Kim SY, Lim BC, Kim H, Hwang H, Choi JE, Kim KJ, Chae JH
Neuromuscul Disord 2023 May;33(5):425-431. Epub 2023 Mar 23 doi: 10.1016/j.nmd.2023.03.009. PMID: 37087885
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Brain Dev 2016 Mar;38(3):324-30. Epub 2015 Sep 9 doi: 10.1016/j.braindev.2015.08.010. PMID: 26363734

Recent clinical studies

Etiology

Ko YJ, Cho A, Kim WJ, Kim SY, Lim BC, Kim H, Hwang H, Choi JE, Kim KJ, Chae JH
Neuromuscul Disord 2023 May;33(5):425-431. Epub 2023 Mar 23 doi: 10.1016/j.nmd.2023.03.009. PMID: 37087885
D'haenens E, Vergult S, Menten B, Dheedene A, Kooy RF, Callewaert B
Genes (Basel) 2022 Apr 14;13(4) doi: 10.3390/genes13040694. PMID: 35456500Free PMC Article
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Diagnosis

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Therapy

Murakami T, Sato T, Adachi M, Ishiguro K, Shichiji M, Tachimori H, Nagata S, Ishigaki K
Sci Rep 2021 Dec 20;11(1):24229. doi: 10.1038/s41598-021-03781-z. PMID: 34930981Free PMC Article
Murphy LB, Schreiber-Katz O, Rafferty K, Robertson A, Topf A, Willis TA, Heidemann M, Thiele S, Bindoff L, Laurent JP, Lochmüller H, Mathews K, Mitchell C, Stevenson JH, Vissing J, Woods L, Walter MC, Straub V
Ann Clin Transl Neurol 2020 May;7(5):757-766. Epub 2020 Apr 28 doi: 10.1002/acn3.51042. PMID: 32342672Free PMC Article
Ishigaki K, Kato I, Murakami T, Sato T, Shichiji M, Ishiguro K, Ishizuka K, Funatsuka M, Saito K, Osawa M, Nagata S
Brain Dev 2019 Jan;41(1):43-49. Epub 2018 Aug 1 doi: 10.1016/j.braindev.2018.07.012. PMID: 30077507
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Expert Opin Biol Ther 2014 Jun;14(6):809-19. Epub 2014 Mar 12 doi: 10.1517/14712598.2014.896335. PMID: 24620745

Prognosis

Society for Maternal-Fetal Medicine (SMFM), Monteagudo A
Am J Obstet Gynecol 2020 Dec;223(6):B38-B41. Epub 2020 Nov 7 doi: 10.1016/j.ajog.2020.08.184. PMID: 33168220
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Vajsar J, Schachter H
Orphanet J Rare Dis 2006 Aug 3;1:29. doi: 10.1186/1750-1172-1-29. PMID: 16887026Free PMC Article

Clinical prediction guides

Sato T, Awano H, Ishiguro K, Shichiji M, Murakami T, Shirakawa T, Matsuo M, Nagata S, Ishigaki K
Neuromuscul Disord 2021 Mar;31(3):194-197. Epub 2021 Jan 13 doi: 10.1016/j.nmd.2021.01.005. PMID: 33563515
Kuwayama R, Suzuki Y, Nishikawa M, Kimizu T, Nakajima K, Ikeda T, Mogami Y, Yanagihara K
Brain Dev 2021 Jan;43(1):106-110. Epub 2020 Jul 25 doi: 10.1016/j.braindev.2020.06.017. PMID: 32723526
Murphy LB, Schreiber-Katz O, Rafferty K, Robertson A, Topf A, Willis TA, Heidemann M, Thiele S, Bindoff L, Laurent JP, Lochmüller H, Mathews K, Mitchell C, Stevenson JH, Vissing J, Woods L, Walter MC, Straub V
Ann Clin Transl Neurol 2020 May;7(5):757-766. Epub 2020 Apr 28 doi: 10.1002/acn3.51042. PMID: 32342672Free PMC Article
Muntoni F, Torelli S, Wells DJ, Brown SC
Curr Opin Neurol 2011 Oct;24(5):437-42. doi: 10.1097/WCO.0b013e32834a95e3. PMID: 21825985
Muntoni F, Torelli S, Brockington M
Neurotherapeutics 2008 Oct;5(4):627-32. doi: 10.1016/j.nurt.2008.08.005. PMID: 19019316Free PMC Article

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