Infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1)

TLDR

SMARD1 is an autosomal recessive spinal muscular atrophy with respiratory distress type 1, the second anterior horn cell disease in infants, caused by mutations in the IGHMBP2 gene on chromosome 11q13. The study reviews clinical features of 29 SMARD1 infants and reports 26 novel IGHMBP2 mutations, emphasizing the need for prenatal diagnosis and clear diagnostic criteria due to poor prognosis. Diagnosis should be considered in infants with non‑5q SMA, neuropathy, muscle weakness, or unexplained respiratory distress, and consanguineous parents of sudden infant death syndrome cases should be screened for IGHMBP2 mutations. Early symptoms include intrauterine growth retardation, weak cry, and foot deformities, with most patients presenting at 1–6 months with diaphragmatic paralysis‑induced respiratory distress, progressive distal lower‑limb weakness, and involvement of sensory and autonomic nerves.

Abstract

Abstract Autosomal recessive spinal muscular atrophy with respiratory distress type 1 (SMARD1) is the second anterior horn cell disease in infants in which the genetic defect has been defined. SMARD1 results from mutations in the gene encoding the immunoglobulin μ‐binding protein 2 ( IGHMBP2 ) on chromosome 11q13. Our aim was to review the clinical features of 29 infants affected with SMARD1 and report on 26 novel IGHMBP2 mutations. Intrauterine growth retardation, weak cry, and foot deformities were the earliest symptoms of SMARD1. Most patients presented at the age of 1 to 6 months with respiratory distress due to diaphragmatic paralysis and progressive muscle weakness with predominantly distal lower limb muscle involvement. Sensory and autonomic nerves are also affected. Because of the poor prognosis, there is a demand for prenatal diagnosis, and clear diagnostic criteria for infantile SMARD1 are needed. The diagnosis of SMARD1 should be considered in infants with non‐5q spinal muscular atrophy, neuropathy, and muscle weakness and/or respiratory distress of unclear cause. Furthermore, consanguineous parents of a child with sudden infant death syndrome should be examined for IGHMBP2 mutations.