FKTN gene

Overview
Microphthalmia, anophthalmia, coloboma (MAC)
Anterior segment dysgenesis
Congenital cataracts
Congenital glaucoma
References

Overview

Gene (OMIM No.)	FKTN (#607440)
Function of gene/protein	Protein: fukutin (FKTN) FKTN is important for the glycosylation (converting carbohydrates to glycoproteins) of alpha-dystroglycan (DAG1) 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, 4 (#253800) Also known as Walker-Warburg syndrome (WWS)/Muscle Eye Brain Disease (MEB)/ Fukuyama type Congenital Muscular Dystrophy (FCMD) Muscular dystrophy-dystroglycanopathy (congenital without mental retardation), type B, 4 (#613152) Muscular dystrophy-dystroglycanopathy (limb girdle), type C, 4 (#611588) Defects in the glycosylation of alpha-dystroglycans cause 3 overlapping syndromes/dystroglycanopathies: WWS, MEB and FCMD WWS—most severe phenotype; MEB—intermediate phenotype; FCMD—mildest phenotype Phenotype severity is determined by the extent which the mutation affects DAG1 glycosylation Cardiomyopathy, dilated 1X (#611615)
Inheritance	Autosomal recessive
Ocular features	Microphthalmia, anophthalmia, coloboma (MAC) spectrum Congenital cataracts Anterior segment dysgenesis Congenital glaucoma Persistent foetal vasculature Retinal dysplasia Retinal detachment Optic atrophy High myopia
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 Dilated cardiomyopathy with mild or absent motor weakness and normal intelligence have been reported
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 diagnosis	Next generation sequencing Targeted gene panels Whole genome sequencing
Management	Ocular Management of MAC Management of congenital cataract Management of anterior segment dysgenesis Management of congenital glaucoma Surgery for dysplastic retina does not confer any visual benefit Rhegmatogenous retinal detachment associated with MEB may be amenable to scleral buckling or vitrectomies Systemic Multidisciplinary approach
Therapies under research	None at present
Further information	Medline Plus

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References

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
Toda T, Kobayashi K, Takeda S, et al. Fukuyama-type congenital muscular dystrophy (FCMD) and alpha-dystroglycanopathy. Congenital anomalies 2003; 43: 97–104
Kondo-Iida E, Kobayashi K, Watanabe M, et al. Novel Mutations and Genotype-Phenotype Relationships in 107 Families With Fukuyama-Type Congenital Muscular Dystrophy (FCMD). Hum Mol Genet 1999; 8: 2303–2309
Beltrán-Valero De Bernabé D, Van Bokhoven H, Van Beusekom E, et al. A homozygous nonsense mutation in the Fukutin gene causes a Walker-Warburg syndrome phenotype. J Med Genet 2003; 40: 845–848
Murakami T, Hayashi YK, Noguchi S, et al. Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness. Ann Neurol. 2006;60(5):597-602
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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