Divergent Phenotypes with Same CHRNE Mutation in Two Siblings with Congenital Myasthenic Syndrome

Abstract

Background: Congenital myasthenic syndrome is a rare inherited neuromuscular disorder resulting in abnormal weakness and fatigue on exertion with onset at or shortly after birth or in early childhood. Clinical Description: A 2-year-old boy presented to us with respiratory failure, having a history of recurrent respiratory tract infections and underlying isolated motor delay. His 7-year-old elder sister had undiagnosed generalized weakness. Management and Outcome: While the index case was being stabilized with mechanical ventilation, his elder sibling was evaluated. Ptosis was noted in her, which improved with neostigmine. Examination and laboratory investigations ruled out other differentials. Clinical exome sequencing was sent which showed homozygous CHRNE ENST00000649488.2.c.1367_1369del. (p.Asn456del) resulting in acetylcholine receptor deficiency. Both siblings were started on oral pyridostigmine and salbutamol, resulting in improvement in muscle weakness over 3 months and 4 months in younger and older sibling, respectively. Conclusion: Recurrent respiratory insufficiency when associated with motor delay may be suggestive of a neuromuscular disorder. Even siblings with the same mutation may have different levels of severity of clinical manifestation.

Keywords

• genetics
• neuromuscular weakness
• pediatric
• respiratory insufficiency