Clinical and neurophysiological data of 11 patients (4 males, 7 females) with congenital myasthenic syndromes (CMS) diagnosed between 1994 and 2000 are reported from Great Ormond Street Hospital, London, UK. Eight presented immediately after birth and 3 by 10 months of age. Common characteristics included profound hypotonia (9/11 patients), arthrogryposis (8), absent tendon reflexes (5), ptosis (7), bulbar signs (8), recurrent apnea or asthma attacks (8), ventilator at birth (7), seizures (3), and poor response to treatment with death at 1-17 months of age (5) or ventilator dependency (2). Four patients survive with motor delay at 8-38 month follow-up. An edrophonium test was positive in 3 of 6 tested, and 8 of 11 responded partially to pyridostigmine. Diagnosis was confirmed by a decrement response after repetitive nerve stimulation or by increased instability and jitter after single fiber EMG stimulation. A positive family history with an undiagnosed neuromuscular disorder and death of at least one previous sibling was obtained in 5 patients. None of the clinical and neurophysiological characteristics was correlated with outcome. Except for one patient with a fast channel CMS, none was classified on a molecular basis as a previously recognized subtype of CMS. [1]

COMMENT. In a series of 51 childhood-onset patients with myasthenia gravis (MG), reported from the Massachusetts General Hospital [2], 35 had juvenile MG with symptoms beginning after the first year of life, 10 born to mothers with MG had neonatal transient myasthenic syndrome, and 6 whose mothers were unaffected had neonatal persistent (congenital) myasthenia. In this earlier series of cases, congenital myasthenic syndrome (CMS) was distinguished from the neonatal transient form by absence of MG in the mother, less severe generalized muscle weakness, and a poor response to anticholinesterase treatment. Ptosis, ophthalmoplegia and weakness of facial and masticatory muscles persist through childhood in to adult life. The family history may be positive for MG in siblings and cousins.

Since this clinical description of the congenital myasthenic syndrome in 1960, and the subsequent discovery of an autoimmune mechanism for MG, the absence of antibodies against the acetylcholine receptor further delineate the congenital syndrome. Engel and his colleagues have identified several CMS subtypes, including Lambert-Eaton CMS, end-plate AchE deficiency, slow and fast channel syndromes, and AchR deficiency [3, 4]. See Progress in Pediatric Neurology III, PNB Publishers, 1997;346-349, for further case reports and commentaries on CMS. The identification of subtypes of the CMS is complex and requires studies of the kinetics of acetylcholine receptors (AchR), and ultrastructure of the endplate. Nevertheless, with an increased awareness of the syndrome, a diagnosis can be determined on clinical and neurophysiological grounds, leading to earlier treatment intervention and better genetic counseling.