Infantile Hypotonia and Respiratory Failure with Missense Variant in IGHMBP2 Gene: A Case of SMARD1 Disease

Background: Infantile-onset hypotonia could be due to genetic causes of neuromuscular diseases. We report an infant with spinal muscular atrophy with respiratory distress type 1 (SMARD1), which is a less-known, rare, severe, progressive congenital neuromuscular disease, manifesting after the initial months of life, with symmetrical distal limb weakness, muscle atrophy, and diaphragmatic paralysis. Clinical Description: A 9-month-old male, with developmental delay and failure to thrive, was referred for failure to wean from respiratory support. He had profound hypotonia, especially in the distal muscles of the lower limbs, with foot contracture and normal cranial nerves and other systems. Management and Outcome: Routine investigations and thyroid functions were normal. Chest X-ray showed eventration of diaphragm, magnetic resonance imaging revealed cerebral atrophy and cerebellar infarct. Electroneuromyography confirmed generalized sensory and motor axonal neuropathy. Whole exome sequencing detected a homozygous variant of uncertain significance in the IGHMBP2 gene. Considering the infantile onset, predominant distal muscle weakness, ventilator dependency, and diaphragmatic palsy, a diagnosis of SMARD was made. An elective tracheostomy was performed, and the child transitioned to bilevel positive airway pressure. Conclusion: This case creates awareness about SMARD1 disease, which may be considered a differential in infants with hypotonia and ventilator dependency, especially with distal muscle weakness and diaphragmatic palsy. Genetic analysis aids diagnosis.