Walker-Warburg Syndrome

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Classification according to ICD-10
G71.2 Congenital myopathies
ICD-10 online (WHO version 2019)

The Walker-Warburg syndrome ( WWS ) is a muscle disorder , to the group of congenital muscular dystrophies or to which subgroup the Dystroglykanopathien belongs. It is a rare genetic disease that autosomal - recessive inherited.

Synonyms are:

  • HARD + E syndrome
  • Cerebro-ocular dysplasia
  • Chemke syndrome
  • Pagon syndrome
  • Warburg syndrome

The Walker-Warburg syndrome is genetically very heterogeneous. Different mutations were found in a total of 6 different genes that lead to a Walker-Warburg phenotype. Clinically, Walker-Warburg syndrome is characterized by severe muscular dystrophy and malformations of the brain ( aqueduct stenosis ) and eyes ( persistent hyperplastic primary vitreus ). Symptoms of the disease are already clearly visible at birth. The disease leads to death within the first two to three years of life. No causal therapy is known.

root cause

The Walker-Warburg syndrome is caused by mutations caused and autosomal - recessive inherited. Several mutations are known in a total of 6 different genes, the gene products of which are proteins of the same name: POMT1 (protein O-mannosyl-transferase 1), POMT2 (protein O-mannosyl-transferase 2), POMGNT1 (protein O-linked-mannose beta-1 , 2-N-acetylglucosaminyltransferase 1), Fukutin , FKRP (Fukutin related protein) and LARGE (glycosyltransferase-like protein LARGE1).

OMIM classification

According to the latest classification of Online Mendelian Inheritance in Man from 2011, Walker-Warburg syndrome and the somewhat milder muscle-eye-brain disease (MEB), with mutations in the same 6 Genes can be detected, combined into a group of diseases and referred to as Congenital Muscular Dystrophy-Dystroglycanopathy with Brain and Eye Anomalies Type A (MDDGA). Depending on the affected gene, the diseases are numbered from 1 to 6:

  • MDDGA1: POMT1
  • MDDGA2: POMT2
  • MDDGA3: POMGNT1
  • MDDGA4: Fukutin
  • MDDGA5: Fukutin related protein (FKRP)
  • MDDGA6: LARGE1

Medical history

Walker-Warburg syndrome was named after Arthur Earl Walker and Mette Warburg . Walker first described the syndrome in 1942. Warburg published another paper on the syndrome in 1972 with more recent findings.

literature

Web links

Individual evidence

  1. ^ B. Leiber: The clinical syndromes. Syndromes, sequences and symptom complexes. Edited by G. Burg, J. Kunze, D. Pongratz, PG Scheurlen, A. Schinzel, J. Spranger, 7th edition. Urban & Schwarzenberg 1990, ISBN 3-541-01727-9 .
  2. ↑ D. Beltrán-Valero de Bernabé, S. Currier et al. a .: 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).
  3. ↑ DS Kim, YK Hayashi et al. a .: 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 .
  4. ↑ J. van Reeuwijk, M. Janssen u. a .: POMT2 mutations cause alpha-dystroglycan hypoglycosylation and Walker-Warburg syndrome. In: Journal of Medical Genetics Volume 42, Number 12, December 2005, pp. 907-912, ISSN  1468-6244 . doi: 10.1136 / jmg.2005.031963 . PMID 15894594 . PMC 173596 (free full text).
  5. ↑ a b E. Clement, E. Mercuri u. a .: Brain involvement in muscular dystrophies with defective dystroglycan glycosylation. In: Annals of neurology Volume 64, Number 5, November 2008, pp. 573-582, ISSN  1531-8249 . doi: 10.1002 / ana.21482 . PMID 19067344 .
  6. ↑ a b c C. Godfrey, E. Clement et al. a .: 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 .
  7. ^ R. Biancheri, E. Bertini et al. a .: POMGnT1 mutations in congenital muscular dystrophy: genotype-phenotype correlation and expanded clinical spectrum. In: Archives of Neurology Volume 63, Number 10, October 2006, pp. 1491-1495, ISSN  0003-9942 . doi: 10.1001 / archneur.63.10.1491 . PMID 17030669 .
  8. ↑ E. Mercuri, S. Messina et al. a .: 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 .
  9. ↑ F. Silan, M. Yoshioka et al. a .: A new mutation of the fukutin gene in a non-Japanese patient. In: Annals of neurology. Volume 53, Number 3, March 2003, pp. 392-396, ISSN  0364-5134 . doi: 10.1002 / ana.10491 . PMID 12601708 .
  10. ^ DB de Bernabé, H. van Bokhoven u. a .: A homozygous nonsense mutation in the fukutin gene causes a Walker-Warburg syndrome phenotype. In: Journal of medical genetics. Volume 40, Number 11, November 2003, pp. 845-848, ISSN  1468-6244 . PMID 14627679 . PMC 173530 (free full text).
  11. ^ RP Cotarelo, MC Valero et al. a .: Two new patients bearing mutations in the fukutin gene confirm the relevance of this gene in Walker-Warburg syndrome. In: Clinical genetics. Volume 73, Number 2, February 2008, pp. 139-145, ISSN  1399-0004 . doi: 10.1111 / j.1399-0004.2007.00936.x . PMID 18177472 .
  12. ↑ B. Cormand, H. Pihko et al. a .: Clinical and genetic distinction between Walker-Warburg syndrome and muscle-eye-brain disease. In: Neurology. Volume 56, Number 8, April 2001, pp. 1059-1069, ISSN  0028-3878 . PMID 11320179 .
  13. ↑ J. van Reeuwijk, PK Grewal u. a .: Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome. In: Human genetics. Volume 121, Number 6, July 2007, pp. 685-690, ISSN  0340-6717 . doi: 10.1007 / s00439-007-0362-y . PMID 17436019 . PMC 191424 (free full text).
  14. ^ 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 .
  15. ↑ MDDGA1.  In: Online Mendelian Inheritance in Man . (English)
  16. ↑ MDDGA2.  In: Online Mendelian Inheritance in Man . (English)
  17. ↑ MDDGA3.  In: Online Mendelian Inheritance in Man . (English)
  18. ↑ MDDGA4.  In: Online Mendelian Inheritance in Man . (English)
  19. ↑ MDDGA5.  In: Online Mendelian Inheritance in Man . (English)
  20. ↑ MDDGA6.  In: Online Mendelian Inheritance in Man . (English)
  21. ↑ AE Walker: lissencephaly . In: Archives of Neurology and Psychiatry , Chicago, 1942, 48, pp. 13-29.
  22. ^ Hydrocephaly, congenital retinal non-attachment and congenital falciform fold. In: American Journal of Ophthalmology. Chicago, 1978, 85, pp. 88-94.
  23. ↑ Susan E. Sparks, Diana M. Escolar: Congenital muscular dystrophies . In: Robert Griggs: Muscular Dystrophies. (= Handbook of Clinical Neurology. Volume 101). 3. Edition. Elsevier, 2011, ISBN 978-0-08-045031-5 , pp. 59-60.