REGISTRIES AND CARE OF NEUROMUSCULAR DISORDERS: P.288Diagnosis, management and outcome of severe congenital onset neuromuscular disorders in a series of 50 infants

Abstract

Congenital onset neuromuscular disorders (NMD) are a heterogeneous group of diseases including congenital muscular dystrophies (CMD), congenital myopathies (CM), congenital myotonic dystrophy, congenital myasthenic syndromes (CMS) and metabolic myopathies. These are characterised by onset before or at birth. Final molecular diagnosis is often delayed causing a direct impact on outcome of these children. We aimed to clinically characterise a series of infants less than three months old referred to the neuromuscular service from 2010 to 2017 and study their outcomes to develop standards of care for this group. Only those with severe symptoms were included. 50 infants less than three months-old were seen. Majority were male (68%). Antenatal problems were noted in 38 (76%). 29 (58%) had hypotonia, 28 (56%) weakness and 32 (64%) had contractures. Feeding difficulties were noted in 37 (74%) and respiratory insufficiency in 39 (78%). Contractures and weakness were more prevalent among those with a final NMD diagnosis (contractures: 72% vs 56%; weakness: 72% vs 40%). None with a final non-NMD diagnosis had contractures. CK was abnormal in 3 (6%), Neurophysiology was abnormal in 39 (93%).Muscle biopsy was the single most helpful investigation. This was abnormal in 29 and diagnostic in 13 (39%). Final molecular diagnosis was achieved in 27(54%) at a mean age of 5.5 months, confirming a NMD in 25 (50%; CM: 14 (28%); CMD: 7 (14%); SMA: 2 (4%); CMS: 2 (4%)). 21 (41%) remain undiagnosed despite extensive testing. 22 (44%) died with 12 unexpected deaths. 20 (68%) required NG feeding/gastrostomy and 14 (48%) are on respiratory support. At last follow-up only 5 had achieved independent ambulation. Our data highlights weakness and contractures as the key features of congenital NMD. Muscle biopsy is recommended early to minimise delays in diagnosis. This group of disorders is associated with high morbidity and mortality and early introduction of respiratory surveillance is recommended.