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Walker-Warburg congenital muscular dystrophy

MedGen UID:
75553
Concept ID:
C0265221
Disease or Syndrome
Synonyms: Muscular dystrophy-dystroglycanopathy, type A; Walker-Warburg syndrome
SNOMED CT: Hydrocephalus, agyria and retinal dysplasia (111504002); Walker Warburg syndrome (111504002); Walker-Warburg congenital muscular dystrophy (111504002); HARD (hydrocephalus, agyria, retinal dysplasia) syndrome (111504002)
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).
 
Monarch Initiative: MONDO:0000171
OMIM®: 236670
OMIM® Phenotypic series: PS236670
Orphanet: ORPHA899

Definition

Walker-Warburg syndrome is an inherited disorder that affects development of the muscles, brain, and eyes. It is the most severe of a group of genetic conditions known as congenital muscular dystrophies, which cause muscle weakness and wasting (atrophy) beginning very early in life. The signs and symptoms of Walker-Warburg syndrome are present at birth or in early infancy. Because of the severity of the problems caused by Walker-Warburg syndrome, most affected individuals do not survive past childhood.

Walker-Warburg syndrome affects the skeletal muscles, which are muscles the body uses for movement. Affected babies have weak muscle tone (hypotonia) and are sometimes described as "floppy." The muscle weakness worsens over time.

Walker-Warburg syndrome also affects the brain; individuals with this condition typically have a brain abnormality called cobblestone lissencephaly, in which the surface of the brain lacks the normal folds and grooves and instead develops a bumpy, irregular appearance (like that of cobblestones). These individuals may also have a buildup of fluid in the brain (hydrocephalus) or abnormalities of certain parts of the brain, including a region called the cerebellum and the part of the brain that connects to the spinal cord (the brainstem). These changes in the structure of the brain lead to significantly delayed development and intellectual disability. Some individuals with Walker-Warburg syndrome experience seizures.

Eye abnormalities are also characteristic of Walker-Warburg syndrome. These can include unusually small eyeballs (microphthalmia), enlarged eyeballs caused by increased pressure in the eyes (buphthalmos), clouding of the lenses of the eyes (cataracts), and problems with the nerve that relays visual information from the eyes to the brain (the optic nerve). These eye problems lead to vision impairment in affected individuals. [from MedlinePlus Genetics]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVWalker-Warburg congenital muscular dystrophy

Professional guidelines

PubMed

Wang P, Jin P, Zhu L, Chen M, Qian Y, Zeng W, Wang M, Xu Y, Xu Y, Dong M
J Gene Med 2022 May;24(5):e3417. Epub 2022 Apr 6 doi: 10.1002/jgm.3417. PMID: 35338537Free PMC Article
Sato T, Murakami T, Ishiguro K, Shichiji M, Saito K, Osawa M, Nagata S, Ishigaki K
Brain Dev 2016 Mar;38(3):324-30. Epub 2015 Sep 9 doi: 10.1016/j.braindev.2015.08.010. PMID: 26363734
Brasseur-Daudruy M, Vivier PH, Ickowicz V, Eurin D, Verspyck E
Pediatr Radiol 2012 Apr;42(4):488-90. Epub 2011 Oct 15 doi: 10.1007/s00247-011-2242-9. PMID: 22002842

Recent clinical studies

Etiology

Varagur K, Sanka SA, Strahle JM
Neurosurg Clin N Am 2022 Jan;33(1):67-79. doi: 10.1016/j.nec.2021.09.006. PMID: 34801143Free PMC Article
Song D, Dai Y, Chen X, Fu X, Chang X, Wang N, Zhang C, Yan C, Zheng H, Wu L, Jiang L, Hua Y, Yang H, Wang Z, Dai T, Zhu W, Han C, Yuan Y, Kobayashi K, Toda T, Xiong H
Clin Genet 2021 Mar;99(3):384-395. Epub 2021 Jan 19 doi: 10.1111/cge.13886. PMID: 33200426
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Reed UC
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Diagnosis

Song D, Dai Y, Chen X, Fu X, Chang X, Wang N, Zhang C, Yan C, Zheng H, Wu L, Jiang L, Hua Y, Yang H, Wang Z, Dai T, Zhu W, Han C, Yuan Y, Kobayashi K, Toda T, Xiong H
Clin Genet 2021 Mar;99(3):384-395. Epub 2021 Jan 19 doi: 10.1111/cge.13886. PMID: 33200426
Suthar R, Angurana SK, Singh U, Singh P
Neurol India 2018 Nov-Dec;66(6):1849-1850. doi: 10.4103/0028-3886.246262. PMID: 30504606
Falsaperla R, Praticò AD, Ruggieri M, Parano E, Rizzo R, Corsello G, Vitaliti G, Pavone P
Ital J Pediatr 2016 Aug 31;42(1):78. doi: 10.1186/s13052-016-0289-9. PMID: 27576556Free PMC Article
Khalaf SS, Tareef RB
J AAPOS 2006 Oct;10(5):486-8. doi: 10.1016/j.jaapos.2006.06.016. PMID: 17070491
Vajsar J, Schachter H
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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
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
Peiris TJ, Indaram M, Koo E, Soul JS, Hunter DG
J AAPOS 2018 Jun;22(3):242-244.e1. Epub 2018 Mar 16 doi: 10.1016/j.jaapos.2017.12.011. PMID: 29555514
Touznik A, Lee JJ, Yokota T
Expert Opin Biol Ther 2014 Jun;14(6):809-19. Epub 2014 Mar 12 doi: 10.1517/14712598.2014.896335. PMID: 24620745
Taniguchi-Ikeda M, Kobayashi K, Kanagawa M, Yu CC, Mori K, Oda T, Kuga A, Kurahashi H, Akman HO, DiMauro S, Kaji R, Yokota T, Takeda S, Toda T
Nature 2011 Oct 5;478(7367):127-31. doi: 10.1038/nature10456. PMID: 21979053Free PMC Article

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
Reed UC
Arq Neuropsiquiatr 2009 Mar;67(1):144-68. doi: 10.1590/s0004-282x2009000100038. PMID: 19330236
Khalaf SS, Tareef RB
J AAPOS 2006 Oct;10(5):486-8. doi: 10.1016/j.jaapos.2006.06.016. PMID: 17070491
Vajsar J, Schachter H
Orphanet J Rare Dis 2006 Aug 3;1:29. doi: 10.1186/1750-1172-1-29. PMID: 16887026Free PMC Article
Pabuşçu Y, Bulakbasi N, Kocaoğlu M, Uçöz T
Comput Med Imaging Graph 2002 Nov-Dec;26(6):453-8. doi: 10.1016/s0895-6111(02)00026-5. PMID: 12453509

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
Ishigaki K, Ihara C, Nakamura H, Mori-Yoshimura M, Maruo K, Taniguchi-Ikeda M, Kimura E, Murakami T, Sato T, Toda T, Kaiya H, Osawa M
Neuromuscul Disord 2018 Oct;28(10):885-893. Epub 2018 Aug 10 doi: 10.1016/j.nmd.2018.08.001. PMID: 30220444
Sato T, Adachi M, Nakamura K, Zushi M, Goto K, Murakami T, Ishiguro K, Shichiji M, Saito K, Ikai T, Osawa M, Kondo I, Nagata S, Ishigaki K
Neuromuscul Disord 2017 Jan;27(1):45-49. Epub 2016 Sep 20 doi: 10.1016/j.nmd.2016.09.014. PMID: 27818010
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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