Mutation in the Fukutin-Gene (FKTN) as cause of a mild congenital muscular dystrophy

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Aims: Defective glycosylation of alpha-dystroglycan as a cause of congenital or limb-girdle muscular dystrophies trigger a broad clinical spectrum varying from mild adult onset limb-girdle muscular dystrophies without brain malformation and cognitive deficits (LGMD2M) to severe congenital muscular dystrophies including brain malformation and central nervous dysfunction. Seven genes, in which mutations can cause defective glycosylation are currently known; FKRP, POMT1, POMT2, POMGnT1, FKTN, LARGE and DAG1. Outside of Japan only isolated cases of fukutin-related muscular dystrophies (LGMD2M) with childhood onset have been described. A steroid therapy seems to have a positive effect. We report on an 8 year old boy suffering from a mild congenital muscular dystrophy type C4 (MDDGC4) with mutation in the Fukutin-Gene. To our knowledge this has not been described before Methods: Our patient exhibited delayed motor development and muscular hypotonia, both commencing in infancy. Free walking at the age of 23 months. At the age of 18 months a elevated CK was revealed (2985U/l), as well as elevated AST (151U/l), ALT (223U/l) and LDH (1270U/l). With a muscle biopsy showing a dystrophic histologic pattern and the immunehistochemistry illustrating an absent sarcolemnal expression of alpha dystroglycan the genetic analysis of the FKRP gene was initiated, showing a normal genotype. A subsequent analysis of the Fukutin gene identified a stop mutation. A steroid treatmend was recommenden to the parents recently, who rejected this option for now. Results: A subsequent analysis of the Fukutin gene identified a heterozygous in-frame duplication within Exon 5 as well as a heterozygous stop mutation in Exon 6 of the fukutin gene Conclusion: In patients showing motor development delay, as well as significantly elevated CK and a dystrophic histologic pattern in the muscle biopsy while cognitive development and cerebral imaging are normal a fukutin-related myopathy should be considered after exlusion of a mutation of the FKRP gene; particularly, because the diagnosis has therapeutic consequence in terms of steroid treatment.