Myasthenic syndromes: mistaking genetic for acquired

Area of Science:

• Neurology
• Genetics
• Rare Diseases

Background:

• Congenital myasthenic syndromes (CMS) are rare genetic neuromuscular junction disorders.
• DOK7 variants are a frequent cause of CMS, sometimes exacerbated by pyridostigmine treatment.
• Adult-onset CMS can be misdiagnosed as acquired myasthenia gravis.

Purpose of the Study:

• To report two adult cases of DOK7-related CMS initially misdiagnosed as seronegative myasthenia gravis.
• To emphasize the diagnostic challenges and treatment implications of DOK7 CMS in adults.
• To highlight the importance of considering CMS in seronegative myasthenia gravis presentations.

Main Methods:

• Case report of two adult patients with progressive limb girdle weakness.
• Review of clinical history, diagnostic workup, and treatment response.
• Genetic analysis to identify DOK7 pathogenic variants.

Main Results:

• Both patients presented with adult-onset, slowly progressive fatigable limb girdle weakness.
• Initial diagnosis of seronegative myasthenia gravis led to escalating immunosuppressive therapy and pyridostigmine.
• Patients improved significantly after discontinuation of pyridostigmine and immunosuppressants, with salbutamol initiation.
• Genetic testing confirmed DOK7 variants in both individuals.

Conclusions:

• DOK7 CMS should be considered in the differential diagnosis of adult-onset seronegative myasthenia gravis.
• Pyridostigmine can worsen symptoms in DOK7 CMS, necessitating careful medication review.
• Timely diagnosis and targeted treatment are essential for managing DOK7 CMS and improving patient outcomes.