Abstract Details

Title A Rare Case of Congenital Myasthenia Syndrome 11 Caused by a Novel Mutation in RAPSN Diagnosed with Rapid Whole Genome Sequencing (rWGS).

Topic Child Neurology and Developmental Neurology

Presentation(s) P18 - Poster Session 18 (5:30 PM-6:30 PM)

Poster/Presentation
Number 6-004

Objective Report a rare case of congenital myasthenia syndrome type 11 (CMS11) with neonatal onset of respiratory failure.

Background CMS 11 is a disorder of the postsynaptic neuromuscular junction disorder with neonatal onset fatigable muscle weakness. (1) Here we present a newborn with respiratory failure and autosomal recessive CMS 11 with deficiency in Acetylcholine receptor-clustering protein rapsyn, encoded by RAPSN.

Design/Methods NA

Results A female born to non-consanguineous parents presented with respiratory failure after birth. Pregnancy was complicated by polyhydramnios and intrauterine growth restriction. Birth was complicated by Caesarian section due to breech position with noted meconium-stained fluid and nuchal cord. Morphological examination revealed hypertelorism, low-set ears, broad nasal bridge, central hypotonia, joint contractures, minimal movement of extremities, Simian crease bilaterally, absent Moro reflex, absent rooting reflex and weak suckling reflex with preserved deep tendon reflexes. Initial labs were unremarkable. MRI brain revealed no significant anomalies. Acetylcholine receptor binding antibody, muscle-specific kinase and spinal muscular atrophy screen were normal. Rapid whole genome sequencing (rWGS) identified a likely pathogenic nonsense mutation at c.679 G>T (p.Glu227Ter) and two variants of uncertain significance in RAPSN. The synergistic effect of these variants is considered etiopathogenetic. She responded well to Pyridostigmine 1-5 mg/kg/day divided 5 times a day. In addition, our patient was identified to be a carrier of a maternally inherited pathogenic G6PD variant. Mother was unaware of her carrier status for G6PD and received appropriate genetic counseling and genome-driven management recommendations.

Conclusions

CMS11 should be considered in the differential of infants with respiratory concerns, hypotonia, and normal reflexes Diagnostic ultrarapid or rapid whole genome sequencing (ur/rWGS) is recommended for neonates with critical illness of unknown etiology to offer accurate and early effective treatment, prevent associated high morbidity and mortality, and potentially change the lifetime trajectory of the disease. (2)

Authors/Disclosures
Graham K. Reid, DO PRESENTER	Dr. Reid has nothing to disclose.
	No disclosure on file
	No disclosure on file
Kallol K. Set, MD (Dayton Children'S Hospital)	Dr. Set has nothing to disclose.

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