A group of 13 patients with early onset diaphragmatic palsy in association with a progressive neuropathy is presented from Great Ormond Street Hospital for Children, London, UK. Weakness and wasting developed over a period of weeks and showed a distal to proximal progression. The patients shared similar characteristics and diagnostic criteria that included early onset respiratory distress, low birth weight, slow motor nerve conduction velocities, and decrease in size of myelinated fibers on sural nerve biopsy. Mutations in 8 cases tested affected the same gene encoding immunoglobulin mu-binding protein 2 in patients with spinal muscular atrophy with respiratory distress type 1 (SMARD1). Histological examination of the spinal cord in one patient showed no evidence of SMA. Genetic and clinical heterogeneity is suggested. [1]

COMMENT. Infants and neonates presenting with severe respiratory distress and diaphragmatic palsy may have diaphragmatic SMA (SMARD1) or severe infantile axonal neuropathy with respiratory failure (SIANRF). The syndrome is clinically and genetically heterogeneous, some cases having mutations in the IGHMBP2 gene.

Clinical features of 29 infants with SMARD1 and 26 novel IGHMBP2 mutations are reported from Charite, Humboldt University, Berlin [2]. Itrauterine growth retardation, weak cry, and foot deformities were the earliest manifestations. Patients presented at 1 to 6 months with respiratory distress due to diaphragmatic paralysis and progressive muscle weakness, predominantly distal lower limbs. Sensory and autonomic nerves are also affected. Diagnosis of SMARD1 is considered in infants with non-5q SMA, neuropathy, and muscle weakness and/or respiratory distress of unclear cause. Consanguineous parents of a child with SIDS should be checked for IGHMBP2 mutations.

NCS/EMG and muscle biopsy together are of diagnostic value in infants with arthrogryposis multiplex congenital (AMC), when the history, examination, and genetic evaluation are unrevealing [3]. Analysis of 38 patients with AMC seen over a 23-year period at Children’s Hospital, Boston, showed that the disorder was neurogenic in 8, myopathic in 10, other in 12, and unknown in 8. Neither EMG nor biopsy alone had consistently high sensitivities or specificities, but when concordant for neurogenic or myopathic findings, they were more accurate than either test alone.