Özlem Yayıcı Köken, Gökçen Öz Tunçer, Büşranur Çavdarlı, Ahmet Cevdet Ceylan, Ayşe Aksoy, Haluk Topaloğlu

Objective: We present three pediatric-onset cases with homozygous GFPT1 gene mutations, two of which are siblings, who were diagnosed as congenital myasthenic syndrome type 12 with tubular aggregates (CMS12) following molecular genetic studies. Patients and Methods: Patients were referred to our clinic for their progressive proximal weakness, easy fatigability, muscle cramps starting around 9-10 years of age. Currently, they are 22 (Case-1, male), 17 (Case-2, female), and 11 years (Case-3, male), of age, respectively. All patients could walk independently, however gait unsteadiness, and waddling gait were observed. Gower’s sign was positive. Case-1 and 2 also had muscle atrophy and intermittent mild ptosis. Decremental compound motor action potential response to repetitive nerve stimulation and myopathic findings seen on electroneuromyography in Case-1. Patients were referred to the Medical Genetics Department of Ankara City Hospital with a pre-diagnosis of congenital myasthenia. A WES analysis was performed by using xGen Exome Research Panel v2. VCF files were annotated using Qiagen Ingenuity Variant Analysis and Clinical Insight Interpret (QIAGEN GmbH). Results: The same GFPT gene homozygous mutations were determined at c.331C>T in siblings and c.738_739delAG in Case-3. Conclusion: This condition is related to an abnormality of the carbohydrate-deficient glycoprotein in general terms. Muscle cramps along with fatigue and proximal weakness in a progressive manner can be considered as clinical clues. Keywords: GFPT1, congenital myasthenic syndrome, muscle cramps