Belt dystrophy

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Classification according to ICD-10
G71.0 Muscular dystrophy
- pelvic or shoulder girdle shape
ICD-10 online (WHO version 2019)

The term limb- (Engl. Limb-girdle muscular dystrophy, LGMD ) is a group of hereditary muscle diseases ( myopathies ), the common feature of paralysis of the muscles of the shoulder and pelvic girdle are. The shoulder and pelvic girdles are collectively referred to in medicine as the limb girdle . In addition to muscle paralysis, the limb girdle dystrophies meet the criteria of muscular dystrophy . Muscular dystrophy is characterized by remodeling processes in the muscle tissue. The diseases in this group are genetically and clinically heterogeneous. They are caused by different gene mutations and the same gene mutations can produce a very variable clinical picture. The onset of the disease ranges from toddler to advanced adulthood and both mild and severe courses are possible. Girdle dystrophies are rare diseases. Estimates of the incidence (prevalence) of all limb girdle dystrophies range from 1: 14,500 to 1: 123,000.

causes

Girdle dystrophies are caused by genetic defects on different chromosomes . These lead to structural deviation, deficiency or complete absence of various muscle proteins , which leads to chronic damage to the muscle fibers that are frequently used. The main symptom is the increasing weakness and the visible shrinkage of the affected muscle areas.

Classification

The classification that is common today is based on the classification of the genetic mutations or the modified proteins. After the inheritance two groups can be distinguished: the autosomal - dominant inherited limb-girdle muscular dystrophy, LGMD1 and the autosomal recessive inherited limb-girdle muscular dystrophy, LGMD2 .

Autosomal dominant forms of limb girdle dystrophies

The autosomal dominant hereditary girdle dystrophies are relatively rare and account for about 10% of all girdle dystrophies. The diseases usually manifest themselves in adulthood ( adult-onset ) and the clinical course is often less severe compared to the autosomal recessive inherited limb girdle dystrophies.

Type Locate gene Gene product Age of manifestation Guiding symptoms forecast
LGMD1A 5q22-q34 MYOT Myotilin 18-35 Weakness of the leg muscles near the hips; years later, arm muscles are affected; Weakness of the facial and throat muscles in 20%, speech disorders ( dysarthria ) in 25% Wheelchair dependency around 20 years after onset, mostly normal life expectancy
LGMD1B 1q22 LMNA Lamin-A / C 4-30 Weaknesses in the hip and thigh muscles near the hips, in two-thirds of cases conduction disorders of the heart and possibly weak heart muscle with enlargement of the heart (dilated cardiomyopathy ) Lifelong ability to walk, but risk of sudden cardiac death by 50–60 years
LGMD1C 3p25.3 CAV3 Caveolin-3 2-20-70 Muscle weakness close to the trunk, calf cramps, calf pseudohypertrophy likely lifelong walking ability and normal life expectancy
LGMD1D 6q23 OF Desmin 20-25, rarely under 20 Arrhythmia and cardiomyopathy , later additional muscle weaknesses near the trunk Sudden death from AV block , ventricular tachycardia, or cardiomyopathy possible
LGMD1E 7q not known not known 10-30 Leg muscle weakness near the hip
LGMD1F 7q32.1 TNPO3 Transportin 3 under 1–58 Pelvic girdle, shoulder girdle muscle weakness
LGMD1G 4q21 HNRNPDL D-like heterogeneous nuclear ribonucleoprotein 30-47 Pelvic and shoulder girdle weakness, flexion contractures of the toes and fingers
LGMD1H 3p25.1-p23 not known not known

Autosomal recessive forms of limb girdle dystrophies

Type Locate gene Gene product frequency Age of manifestation Guiding symptoms forecast
LGMD2A 15q15.1 CAPN3 Calpain-3 About 10% of all LGMD2, founder mutations : Amish , La Réunion , Basques , Turks 3-10-30 Weakness of the hip and thigh muscles, including the trunk muscles, shoulder muscles often 2–5 years later, often also contractures of the spine , ankles, elbows and hands rapid or slow course, depending on death around the age of 20 possible, otherwise in the 8th decade of life, early onset does not automatically mean rapid progression
LGMD2B 2p13.2 DYSF Dysferlin About 5% of all LGMD2 13-22-35 Weakness especially of the posterior hip and thigh muscles near the hip, 25% calf pseudohypertrophy, 2–10 years later shoulder muscle weakness rapid or slow course, about 30% ability to walk up to 26–54 years, otherwise up to the 8th decade
LGMD2C 13q12.12 SGCG Gamma sarcoglycan 3-12 Muscle weakness in the pelvic girdle earlier than in the shoulder girdle, early calf pseudohypertrophy, later facial muscles may be affected Walking ability 25% 10–15 years, 50% 15–20 years, 25% over 20 years, death possible in the second decade of life
LGMD2D 17q21.33 SGCA Alpha sarcoglycan 1-16, later Increasing muscle weakness in the pelvic girdle and thighs with delayed starting to walk or an unsteady gait similar to Duchenne muscular dystrophy rapid or slow course, ability to walk up to 16-30 years or later, premature death possible if the course progresses rapidly
LGMD2E 4q12 SGCB Beta sarcoglycan 3-12 Pelvic girdle more affected than shoulder girdle, calf pseudohypertrophy rapid or slow course, ability to walk 9–14 years or up to 38 years, death in the 2nd – 3rd Decade of life possible
LGMD2F 5q33-q34 SGCD Delta sarcoglycan 4-10 Increasing muscle weakness in the pelvic girdle and thighs with delayed starting to walk or an unsteady gait similar to Duchenne muscular dystrophy , facial muscles possibly affected, calf hypertrophy Rapid progression with the ability to walk 9–16 years, death possible at the end of the first or in the second decade of life
LGMD2G 7q12 TCAP Telethonin About 3% of all LGMD2 9-15 In addition to hip and thigh muscle weakness, lower leg muscles and arm / shoulder muscles are also affected long walking ability up to 18-25 years after beginning
LGMD2H 9q33.1 TRIM32 E3 ubiquitin protein ligase TRIM32 1st - 3rd decade Pelvic girdle more affected than shoulder girdle, possibly neck or back pain Walking difficulties at 37–46 years of age, wheelchair dependency in the seventh decade of life
LGMD2I 19q13.32 FKRP Fukutin Associated Protein (FKRP) About 6% of all LGMD2 1st – 4th decade Initially weakness of the hip and thigh muscles, later the shoulder and upper arm muscles, calf pseudohypertrophy, muscle pain during exercise, muscle fiber breakdown ( rhabdomyolysis ) very different course, walking ability mostly up to 30 years
LGMD2J 2q31.2 TTN Titin 1st - 3rd decade Muscle weakness and atrophy of the hip and thigh muscles near the hips Loss of walking in the 3rd – 5th Decade of life
LGMD2K 9q34.13 POMT1 Protein O-mannosyl transferase 1
LGMD2L 11p14.3 ANO5 Anoctamine-5 About 25% of LGMD2 in the UK , Founding Mutations : Northern Europeans
LGMD2M 9q31.2 FKTN Fukutin 6 patients
LGMD2N 14q24.3 POMT2 Protein O-mannosyltransferase 2 2 patients
LGMD2O 1p34.1 POMGNT1 Protein-O-mannose-beta-1,2-N-acetylglucosaminyltransferase 1 2 independent patients (1 Irish girl, 1 Belgian boy)
LGMD2P 3p21.31 DAG1 Dystroglycan 1 Turkish patient, homozygous mutation early childhood Belt dystrophy with mental retardation At 16, walking a few meters, IQ 50
LGMD2Q 8q24.3 PLEC1 Plectine 4 members of a Turkish family
LGMD2R 2q35 OF Desmin 2 Turkish clans
LGMD2S 4q35.1 TRAPPC11 TRAPPC11 3 Syrian families, 5 Hutterites
LGMD2T 3p21.31 GMPPB Beta GDP mannose phosphorylase 3 independent patients
LGMD2U 7p21.2 ISPD Isoprenoid synthase domain-containing protein
LGMD2V 17q25.3 ATM Lysosomal Alpha-Glucosidase
LGMD2W 3p21.31 LIMS2 LIM and senescent cell antigen-like-containing domain protein 2 Childhood Limb girdle dystrophy with pseudohypertrophy of the calves and macroglossia , impaired left ventricular function from the 3rd decade
LGMD2X 6q21 BVES Blood vessel epicardial substance (Popeye protein 1) Adulthood

diagnosis

Evidence of alpha-sarcoglycan in A) unaffected muscles, B) absence of the same in LGMD 2D

The derivation of the electrical muscle activity ( electromyography , EMG) provides unspecific evidence of chronic muscle damage ( myopathy ). Imaging methods such as computed tomography (CT) or magnetic resonance tomography (MRT) can show particularly affected muscle groups. A significantly increased creatine kinase is often noticeable in the laboratory . If clinical symptoms are suspected, immunohistochemical or molecular genetic examinations of a muscle biopsy usually help to confirm the diagnosis.

therapy

An established drug therapy is not known for any of the limb girdle dystrophies. Symptomatic treatment focuses on physical therapy measures to maintain muscle strength, to train everyday movements and to prevent contractures. However, maximal strength training is considered unfavorable. Appropriate aids in the form of splints ( orthoses ), walking sticks , walkers or a wheelchair are also important . In the case of misalignments of the feet or the spine, surgical treatment measures can also be considered to restore the ability to walk. If there is an impairment of speech motor skills ( dysarthria ), speech therapy is necessary.

After operations or other circumstances of restricted mobility, early mobilization is important, as prolonged immobilization of patients with limb girdle dystrophy often leads to a loss of the ability to walk. Physiotherapy should be started the day after surgery and carried out consistently.

If the heart is involved, therapy for conduction disorders and other heart diseases may be possible.

Medical history

Most of the time, the term limb girdle dystrophies is traced back to a work by John Nicholas Walton and Frederick John Natrass from 1954. The first descriptions of limb girdle dystrophies go back to the work of Ernst von Leyden and Paul Julius Möbius in 1876 and 1879, respectively.

literature

  • V. Nigro, M. Savarese: Genetic basis of limb-girdle muscular dystrophies: the 2014 update. In: Acta myologica: myopathies and cardiomyopathies: official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases. Volume 33, Number 1, May 2014, pp. 1-12, ISSN  1128-2460 . PMID 24843229 . PMC 4021627 (free full text).
  • E. Pegoraro, EP Hoffman: Limb-Girdle Muscular Dystrophy Overview. GeneReviews [Internet]. University of Washington, Seattle, June 8, 2000, [updated August 30, 2012]. PMID 20301582 .
  • L. Broglio, M. Tentorio et al .: Limb-girdle muscular dystrophy-associated protein diseases. In: The neurologist. Volume 16, Number 6, November 2010, pp. 340-352, ISSN  1074-7931 . doi: 10.1097 / NRL.0b013e3181d35b39 . PMID 21150381 . (Review).
  • CT Rocha, EP Hoffman: Limb-girdle and congenital muscular dystrophies: current diagnostics, management, and emerging technologies. In: Current neurology and neuroscience reports. Volume 10, Number 4, July 2010, pp. 267-276, ISSN  1534-6293 . doi: 10.1007 / s11910-010-0119-1 . PMID 20467841 . (Review).
  • K. Bushby: Diagnosis and management of the limb girdle muscular dystrophies. In: Practical neurology. Volume 9, Number 6, December 2009, pp. 314-323, ISSN  1474-7766 . doi: 10.1136 / jnnp.2009.193938 . PMID 19923111 . (Review).
  • A. Ferbert , W. Kress: Clinic and genetics of the limb girdle dystrophies. In: Medical Genetics. Volume 21, Number 3, 2009, pp. 332–336, doi: 10.1007 / s11825-009-0171-x
  • M. Guglieri, K. Bushby: How to go about diagnosing and managing the limb-girdle muscular dystrophies. In: Neurology India. Volume 56, Number 3, 2008 Jul-Sep., Pp. 271-280, ISSN  0028-3886 . PMID 18974553 . (Review).
  • M. Guglieri, V. Straub et al .: Limb-girdle muscular dystrophies. In: Current Opinion in Neurology . Volume 21, Number 5, October 2008, pp. 576-584, ISSN  1350-7540 . doi: 10.1097 / WCO.0b013e32830efdc2 . PMID 18769252 . (Review).
  • F. Norwood, M. de Visser et al .: EFNS guideline on diagnosis and management of limb girdle muscular dystrophies. In: European journal of neurology. Volume 14, Number 12, December 2007, pp. 1305-1312, ISSN  1468-1331 . doi: 10.1111 / j.1468-1331.2007.01979.x . PMID 18028188 . (Review).
  • V. Straub, K. Bushby: The childhood limb-girdle muscular dystrophies. In: Seminars in pediatric neurology. Volume 13, Number 2, June 2006, pp. 104-114, ISSN  1071-9091 . doi: 10.1016 / j.spen.2006.06.006 . PMID 17027860 . (Review).
  • D. Fischer: Clinical and imaging differential diagnosis of limb girdle dystrophies. In: Klin Neurophysiol. Volume 37, No. 3, 2006, pp. 180-188, doi: 10.1055 / s-2006-940133 .
  • J. Finsterer: Clinic and genetics of the limb girdle dystrophies. In: The neurologist. 2004, Volume 75, Number 12, pp. 1153-1166, doi: 10.1007 / s00115-004-1769-5 .
  • J. Sarparanta et al: Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy. In: Nat Genet. Volume 44, No. 4, Feb 26, 2012, pp. 450-455, S1-2. doi: 10.1038 / ng.1103 .

Web links

Individual evidence

  1. ↑ a b c d e f E. Pegoraro, EP Hoffman: Limb-Girdle Muscular Dystrophy Overview. GeneReviews [Internet]. University of Washington, Seattle, June 8, 2000, updated August 30, 2012. PMID 20301582. "
  2. ↑ A. Ferbert, W. Kress: Clinic and genetics of the limb girdle dystrophies. In: Medical Genetics . Volume 21, Number 3, 2009, pp. 332-336.
  3. ↑ a b c d e V. Nigro, M. Savarese: Genetic basis of limb-girdle muscular dystrophies: the 2014 update. In: Acta myologica: myopathies and cardiomyopathies: official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases. Volume 33, Number 1, May 2014, pp. 1-12, ISSN  1128-2460 . PMID 24843229 . PMC 4021627 (free full text).
  4. ↑ LGMD1A.  In: Online Mendelian Inheritance in Man . (English), accessed September 20, 2013.
  5. ↑ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at U. Schara , W. Mortier: Neuromuscular Diseases (NME). Part 2: Muscular Dystrophies (MD). In: Monthly Pediatrics. Volume 151, 2003, pp. 1321-1341.
  6. ↑ a b LGMD1C.  In: Online Mendelian Inheritance in Man . (English), accessed September 20, 2013.
  7. ↑ LGMD1D.  In: Online Mendelian Inheritance in Man . (English), accessed September 20, 2013.
  8. ↑ LGMD1E.  In: Online Mendelian Inheritance in Man . (English), accessed September 20, 2013.
  9. ↑ LGMD1F.  In: Online Mendelian Inheritance in Man . (English), accessed September 20, 2013.
  10. ↑ MJ Melià, A. Kubota et al .: Limb-girdle muscular dystrophy 1F is caused by a microdeletion in the transportin 3 gene. In: Brain: a journal of neurology. Volume 136, Pt 5, May 2013, pp. 1508-1517, ISSN  1460-2156 . doi: 10.1093 / brain / awt074 . PMID 23543484 . PMC 3634201 (free full text).
  11. ↑ a b LGMD1G.  In: Online Mendelian Inheritance in Man . (English), accessed June 3, 2014.
  12. ↑ a b N. M. Vieira, MS Naslavsky et al .: A defect in the RNA-processing protein HNRPDL causes limb-girdle muscular dystrophy 1G (LGMD1G). In: Human Molecular Genetics . [electronic publication before printing] March 2014, ISSN  1460-2083 . doi: 10.1093 / hmg / ddu127 . PMID 24647604 .
  13. ↑ LGMD1H.  In: Online Mendelian Inheritance in Man . (English), accessed June 3, 2014.
  14. ↑ LGMD2A.  In: Online Mendelian Inheritance in Man . (English), accessed November 13, 2011.
  15. ↑ LGMD2B.  In: Online Mendelian Inheritance in Man . (English), accessed November 13, 2011.
  16. ↑ LGMD2C.  In: Online Mendelian Inheritance in Man . (English), accessed November 13, 2011.
  17. ↑ LGMD2D.  In: Online Mendelian Inheritance in Man . (English), accessed November 13, 2011.
  18. ↑ LGMD2E.  In: Online Mendelian Inheritance in Man . (English), accessed November 13, 2011.
  19. ↑ LGMD2F.  In: Online Mendelian Inheritance in Man . (English), accessed November 13, 2011.
  20. ↑ LGMD2G.  In: Online Mendelian Inheritance in Man . (English), accessed November 13, 2011.
  21. ↑ LGMD2H.  In: Online Mendelian Inheritance in Man . (English), accessed November 13, 2011.
  22. ↑ LGMD2I.  In: Online Mendelian Inheritance in Man . (English), accessed November 13, 2011.
  23. ↑ LGMD2J.  In: Online Mendelian Inheritance in Man . (English), accessed November 13, 2011.
  24. ↑ LGMD2K.  In: Online Mendelian Inheritance in Man . (English), accessed November 13, 2011.
  25. ↑ LGMD2L.  In: Online Mendelian Inheritance in Man . (English), accessed November 13, 2011.
  26. ↑ a b LGMD2M.  In: Online Mendelian Inheritance in Man . (English), accessed October 12, 2013.
  27. ↑ a b LGMD2N.  In: Online Mendelian Inheritance in Man . (English), accessed October 12, 2013.
  28. ↑ a b LGMD2O.  In: Online Mendelian Inheritance in Man . (English), accessed October 12, 2013.
  29. ↑ a b c LGMD2P.  In: Online Mendelian Inheritance in Man . (English), accessed October 12, 2013.
  30. ↑ a b Y. Hara, B. Balci-Hayta et al .: A dystroglycan mutation associated with limb-girdle muscular dystrophy. In: The New England Journal of Medicine . Volume 364, Number 10, March 2011, pp. 939-946, ISSN  1533-4406 . doi: 10.1056 / NEJMoa1006939 . PMID 21388311 . PMC 3071687 (free full text).
  31. ↑ a b LGMD2Q.  In: Online Mendelian Inheritance in Man . (English), accessed October 12, 2013.
  32. ↑ a b LGMD2R.  In: Online Mendelian Inheritance in Man . (English), accessed October 12, 2013.
  33. ↑ a b LGMD2S.  In: Online Mendelian Inheritance in Man . (English), accessed October 12, 2013.
  34. ↑ a b LGMD2T.  In: Online Mendelian Inheritance in Man . (English), accessed October 12, 2013.
  35. ↑ LGMD2X.  In: Online Mendelian Inheritance in Man . (English), accessed July 9, 2016.
  36. ↑ A. Ferbert, W. Kress: Clinic and genetics of limb-girdle muscular dystrophy. In: Medical Genetics. Volume 21, Number 3, 2009, p. 337, doi: 10.1007 / s11825-009-0171-x
  37. ↑ a b A. Ferbert, W. Kress: Clinic and genetics of limb-girdle muscular dystrophy. In: Medical Genetics. Volume 21, Number 3, 2009, p. 336, doi: 10.1007 / s11825-009-0171-x
  38. ↑ JN Walton, FJ Natrass: On the classification, natural history and treatment of the myopathies. In: Brain. 77, 1954, pp. 169-231, doi: 10.1093 / brain / 77.2.169 .
  39. ↑ Hereditary forms of progressive muscular atrophy; Lipomatous muscle hypertrophy. In: Clinic of Spinal Cord Diseases. Vol. 2, A. Hirschwald, Berlin 1876, pp. 525-540.
  40. ↑ Paul Julius Möbius: About the hereditary nervous diseases. Breitkopf and Härtel, 1879.
  41. ↑ A. Ferbert, W. Kress: Clinic and genetics of limb-girdle muscular dystrophy. In: Medical Genetics. Volume 21, Number 3, 2009, p. 332, doi: 10.1007 / s11825-009-0171-x