Phenotypic variability in congenital myasthenic syndrome with GFPT1 mutation.

Background: Congenital myasthenic syndrome (CMS) is phenotypically and genetically different from myasthenia gravis. CMS can present in adolescents and can be treatable. Genetic testing is helpful in diagnosis, and guides therapy, alleviating the need of muscle biopsy. Also, Genetic diagnosis allows a diagnosis of certainty, especially if there is any doubt about a muscular pathology Henceforth, it is an important differential in those presenting with fixed or fluctuating weakness.

Method: Herein, we report two adolescent females with positive Glutamine-fructose-6-phosphate transaminase1( GFPT)mutation(c.322G > A p.Arg111His) with different phenotypic features. One of them presented with dysmorphic features, hyperextensible joints, features suggestive of metabolic myopathy on muscle biopsy and a strongly positive acetylcholine receptor (AChR) antibodies in serum. The second case presented with clinical features typical of congenital limb girdle myasthenic syndrome.

Conclusion: Our case had limb girdle weakness, dysmorphic features, uniquely positive AChR antibody, mitochondrial pathology on muscle biopsy and positive GFPT1 mutation. This phenotype has not been reported previously. Given the condition being potentially treatable, GFPT1 mutation subtype of CMS should be considered in differential diagnosis of limb girdle weakness phenotype even in the absence of family history.