P.127 - Phenotypic heterogeneity in patients with mutations in the IGHMBP2 gene

Abstract

Mutations in immunoglobulin µ-binding protein 2 gene (IGHMBP2) had been linked to spinal muscular atrophy with respiratory distress (SMARD1) and other less severe phenotypes. We present 4 patients with genetically confirmed IGHMBP2 mutations showing phenotypic heterogeneity. The first two cases with early onset SMARD1 phenotype corresponded to one boy and one girl that presented intrauterine growth retardation, early hypotonia and progressive respiratory distress with distal weakness. Nerve conduction studies showed axonal neuropathy. At 6 and 5 months respectively, they suffered a respiratory exacerbation with diaphragmatic eventration. Aggressive care planning including tracheostomy and gastrostomy was taken in the first case. The patient is now 23 yo and presents ophtalmoplegia and flaccid tetraplegia. The second patient received palliative care and died at 6 months of age. In both cases, genetic analysis of IGHMBP2 revealed nonsense homozygous mutation. The third and fourth cases are two Pakistani siblings born from healthy consanguineous parents; a 13 yo girl that presented poor fetal movements, arthrogryposis and loss of ambulation at 2 year of age and a 10 year boy with motor developmental delay and loss of ambulation at 8 y of age. Nerve conduction studies showed distal motor axonal neuropathy. None of them presented respiratory involvement. Genetic testing found a homozygous mutation in IGHMBP2 in both cases. The genotype-phenotype correlation in patients with IGHMBP2 mutations remains unclear. IGHMBP2 mutations should be considered in every child with early-onset distal axonal neuropathy with or without respiratory involvement and the different phenotypes should be taken into account in the genetic counseling.