FKRP gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: fukutin related protein (FKRP)
  • FKRP is important for the glycosylation (converting carbohydrates to glycoproteins) of alpha-dystroglycan (DAG1), a crucial protein involved in the maintenance of tissue structure
  • High level of expression in the brain, skeletal muscles and heart muscle
Clinical phenotype
(OMIM phenotype no.)
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5 (#613153)
  • Also known as Walker-Warburg syndrome (WWS)/Muscle Eye Brain Disease (MEB)
  • Muscular dystrophy-dystroglycanopathy (congenital with or without mental retardation), type B, 5 (#606612)
  • Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5 (#607155)
  • Defects in the glycosylation of alpha-dystroglycans cause 3 overlapping syndromes/dystroglycanopathies: WWS, MEB and Fukuyama type Congenital Muscular Dystrophy (FCMD; #253800)
  • WWS—most severe phenotype; MEB—intermediate phenotype; FCMD—mildest phenotype
  • Phenotype severity is determined by the extent which the mutation affects DAG1 glycosylation
  • Autosomal recessive
Ocular features
Systemic features
  • Congenital muscular dystrophy
  • Brain anomalies (cobblestone lissencephaly, hydrocephalus, hypoplastic cerebellar vermis, macrocephaly, microcephaly or anencephaly)
  • Severe hypotonia
  • Occasional seizures
  • Intellectual disability
  • Developmental delays
  • Patients with WWS have a severely limited lifespan with significant CNS and ocular anomalies
Key investigations
  • B-scan USS to measure axial length to document microphthalmia
  • Electrophysiology to determine visual potential
  • Measurement of intraocular pressure
  • Gonioscopy (if tolerated/EUA) or anterior segment OCT to identify angle abnormalities and any associated anterior segment dysgenesis
  • MRI brain and orbit
  • Systemic assessment with a paediatrician and other relevant specialists
  • Bloods (elevated creatinine kinase)
  • Skeletal muscle biopsy
Molecular diagnosisNext generation sequencing
  • Targeted gene panels
  • Whole genome sequencing
  • Surgery for dysplastic retina does not confer any visual benefit
  • Rhegmatogenous retinal detachment associated with MEB may be amenable to scleral buckling or vitrectomies
  • Multidisciplinary approach
Therapies under research
  • None at present
Further information

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  1.  Esapa CT, Benson MA, Schröder JE, et al. Functional requirements for fukutin-related protein in the Golgi apparatus. Hum Mol Genet 2002; 11: 3319–3331
  2.  Willer T, Inamori KI, Venzke D, et al. The glucuronyltransferase B4GAT1 is required for initiation of LARGE-mediated α-dystroglycan functional glycosylation. Elife 2014; 3: 3941
  3.  Cormand B, Pihko H, Bayés M, et al. Clinical and genetic distinction between Walker-Warburg syndrome and muscle-eye-brain disease. Neurology 2001; 56: 1059–1069
  4.  Beltran-Valero De Bernabé D, Voit T, Longman C, et al. Mutations in the FKRP gene can cause muscle-eye-brain disease and Walker-Warburg syndrome. J Med Genet 2004; 41: e61
  5.  Van Reeuwijk J, Olderode-Berends MJW, Van Den Elzen C, et al. A homozygous FKRP start codon mutation is associated with Walker-Warburg syndrome, the severe end of the clinical spectrum. Clin Genet 2010; 78: 275–281
  6.  Francisco R, Pascoal C, Marques-da-Silva D, et al. Keeping an eye on congenital disorders of O-glycosylation: A systematic literature review. J Inherit Metab Dis. 2019;42(1):29-48

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Updated on November 30, 2020
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