Retrospective Cohort Analysis of Clinical, Molecular, and Histopathologic Characteristics of 275 Patients With Nemaline Myopathy.

BACKGROUND AND

OBJECTIVES

Nemaline myopathy (NM) is a congenital myopathy with a wide severity spectrum, from severe, generalized muscle weakness and respiratory failure in the neonatal period to mild, distal weakness in young adulthood. Eleven genes have been definitively established to cause the condition. Although some recurrent variants have been identified, the overall correlation of genotype with clinical severity in NM remains poor. This poses challenges when counseling families about prognosis after a diagnosis of NM is made. Better clinical and molecular predictors of outcome are needed for clinical trial readiness.

METHODS

A retrospective cohort analysis of 275 patients with a histopathologic diagnosis of NM and/or pathogenic variants in NM-associated genes was performed to identify relationships between early clinical findings and long-term outcomes, including need for respiratory and feeding support.

RESULTS

Early clinical predictors of long-term outcomes were identified: patients with hypotonia at birth had increased odds of requiring gastrostomy tubes, and patients with respiratory distress at birth had increased odds of requiring both gastrostomy tubes and invasive ventilation. Individuals with ACTA1-NM were more likely to require feeding tubes and invasive ventilation in the first year of life compared with those with NEB-related NM, but the odds of requiring invasive ventilation were similar after the first year of age. Additional clinical information is presented by genotype and severity class.

DISCUSSION: Neonatal findings of individuals with NM are correlated with long-term clinical outcomes, and there are some relationships between genotype and disease severity. Prospective longitudinal studies are needed to confirm these findings and evaluate for additional early clinical predictors of prognosis.