Belt dystrophy 2K

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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 limb-2K (LGMD2K) is a very rare disease from the group of limb-girdle muscular dystrophy . According to the classification of Online Mendelian Inheritance in Man of 2011, the disease is also called limb girdle muscular dystrophy type Dystroglykanopathie C1 (Engl. Limb-Girdle Muscular Dystrophy Dystroglycanopathy Type C1 , MDDGC1 ), respectively.

root cause

The LGMD2K is caused by mutations in POMT1 gene causes and autosomal - recessive inherited. POMT1 codes for a glycosyltransferase . The result is impaired glycosylation of α-dystroglycan , which is why the disease is also counted among the dystroglycanopathies .

Clinical manifestations

Clinically, the disease is characterized by slowly advancing limb girdle dystrophy with slightly delayed motor development , microcephaly without structural malformations of the brain and mental retardation . The onset of the disease is between the first and sixth year of life. In the few patients described so far, the intelligence quotient was between 50 and 76.

Diagnosis

The disease can be verified by molecular genetics, i.e. by detecting mutations in the POMT1 gene. The histological examination of the muscle tissue shows unspecific signs of muscular dystrophy. As with other dystroglycanopathies, a reduced glycosylation of the α-dystroglycan can be demonstrated immunohistologically . The creatine kinase concentration in the blood serum is increased.

Demarcation

Mutations in the POMT1 gene can lead to a wide clinical spectrum with different phenotypes. In addition to LGMD2K, congenital muscular dystrophies can also occur, the clinical course of which is significantly more severe. In congenital muscular dystrophy dystroglycanopathy with mental retardation type B1 (MDDGB1), the disease already begins congenitally and, in addition to a limb girdle dystrophy, is characterized by significantly delayed motor development and mental retardation. In the congenital muscular dystrophies POMT1-associated Walker-Warburg syndrome and POMT1-associated muscle-eye-brain disease , the patients are affected even more severely. In addition to the congenital onset of muscular dystrophy, severe malformations of the brain and eyes also occur.

Individual evidence

  1. ^ Anthony A. Amato: Other limb-gridle muscular dystrophies . I .: Robert Griggs: Muscular Dystrophies. 3. Edition. Elsevier, 2011, ISBN 978-0-08-045031-5 , p. 120. (Handbook of Clinical Neurology, Volume 101)
  2. ^ J. Amberger, C. Bocchini, A. Hamosh: A new face and new challenges for Online Mendelian Inheritance in Man (OMIM®). In: Human mutation. Volume 32, Number 5, May 2011, pp. 564-567, ISSN  1098-1004 . doi: 10.1002 / humu.21466 . PMID 21472891 .
  3. ↑ MDDGC1.  In: Online Mendelian Inheritance in Man . (English)
  4. ↑ B. Balci, G. Uyanik et al: An autosomal recessive limb girdle muscular dystrophy (LGMD2) with mild mental retardation is allelic to Walker-Warburg syndrome (WWS) caused by a mutation in the POMT1 gene. In: Neuromuscular disorders: NMD. Volume 15, Number 4, April 2005, pp. 271-275, ISSN  0960-8966 . doi: 10.1016 / j.nmd.2005.01.013 . PMID 15792865 .
  5. ↑ M. Lommel, S. Cirak et al: Correlation of enzyme activity and clinical phenotype in POMT1-associated dystroglycanopathies. In: Neurology. Volume 74, Number 2, January 2010, pp. 157-164, ISSN  1526-632X . doi: 10.1212 / WNL.0b013e3181c919d6 . PMID 20065251 .
  6. ↑ P. Dinçer, B. Balci et al .: A novel form of recessive limb girdle muscular dystrophy with mental retardation and abnormal expression of alpha-dystroglycan. In: Neuromuscular disorders: NMD. Volume 13, Number 10, December 2003, pp. 771-778, ISSN  0960-8966 . PMID 14678799 .
  7. ^ UC Reed: Congenital muscular dystrophy. Part I: a review of phenotypical and diagnostic aspects. In: Arquivos de neuro-psiquiatria. Volume 67, Number 1, March 2009, pp. 144-168, ISSN  1678-4227 . PMID 19330236 . (Review).
  8. ↑ MDDGB1.  In: Online Mendelian Inheritance in Man . (English)
  9. ↑ D. Beltrán-Valero de Bernabé, S. Currier et al .: Mutations in the O-mannosyltransferase gene POMT1 give rise to the severe neuronal migration disorder Walker-Warburg syndrome. In: American Journal of Human Genetics . Volume 71, Number 5, November 2002, pp. 1033-1043, ISSN  0002-9297 . doi: 10.1086 / 342975 . PMID 12369018 . PMC 419999 (free full text).
  10. ↑ DS Kim, YK Hayashi et al: POMT1 mutation results in defective glycosylation and loss of laminin-binding activity in alpha-DG. In: Neurology. Volume 62, Number 6, March 2004, pp. 1009-1011, ISSN  1526-632X . PMID 15037715 .
  11. ↑ C. Godfrey, E. Clement et al .: Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan. In: Brain: a journal of neurology. Volume 130, Pt 10 October 2007, pp. 2725-2735, ISSN  1460-2156 . doi: 10.1093 / brain / awm212 . PMID 17878207 .
  12. ^ E. Mercuri, S. Messina et al.: Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study. In: Neurology. Volume 72, Number 21, May 2009, pp. 1802-1809, ISSN  1526-632X . doi: 10.1212 / 01.wnl.0000346518.68110.60 . PMID 19299310 .
  13. ↑ MDDGA1.  In: Online Mendelian Inheritance in Man . (English)