Congenital myathenic syndrome associated with COLQ mutation: an interesting report

Abstract

Congenital myasthenic syndromes (CMS) are a rare inherited disorder of neuromuscular transmission associated with abnormal weakness and fatiguability on exertion. Usually present from birth/childhood and are characterized by exercise induced weakness and easy fatigability (regular activities). We present rare and interesting case of CMS. A 26 year old male, born out of non-consanguinous marriage with normal birth history, presented to us with motor developmental delay, was a floppy infant with poor suck and cry with bilateral ptosis, gradually progressive bilateral lower limb weakness since 10 years of age, bilateral upper limb weakness since 12 years of age with easy fatiguability on exertion, ptosis, neck weakness without any fasciculations, bladder bowel involvement or sensory complaints with a negative history family with a worsening of symptoms on pyridostigmine trial. Routine nerve conduction studies were normal. There was decremental response in RNST. His Ach receptor antibody and Musk antibody status were negative. In view of above findings he was subjected to genetic analysis where targeted gene sequencing was done, which revealed a homozygous mutation in the intron 12 of COLQ gene which was pathogenic. The COLQ gene is located at the short arm of chromosome 3. Its AR mutation causes synaptic form of CMS. The age of presentation is variable from early childhood to 4–5th decade with fatiguable weakness, ptosis and respiratory crises. They have variable response to treatment and hence genetic characterization is of utmost importance!