Article

Interfamilial phenotypic heterogeneity in SMARD1.

Department of Neurology, Evelina Children's Hospital, Lambeth Palace Road, London SE1 7EH, UK.
Neuromuscular Disorders (Impact Factor: 3.13). 02/2009; 19(3):193-5. DOI: 10.1016/j.nmd.2008.11.013
Source: PubMed

ABSTRACT Spinal muscular atrophy with respiratory distress (SMARD1: mu-binding protein 2 gene mutation) is characterised by low birth weight, progressive distal limb weakness, diaphragmatic paralysis and subsequent respiratory failure manifesting before 13 months of age. Our case report illustrates marked phenotype variability in two siblings with an identical genetic mutation of SMARD1, one of whom died of fulminant respiratory failure aged 6 months, whereas the other shows limb weakness but, only mild sleep hypoventilation aged 12 years. This suggests other compensatory mechanisms may play a role in modifying SMARD1; broadening our perception of phenotype. Therefore, SMARD1 phenotype should be considered in cases of atypical spinal muscular atrophy even in the absence of overt diaphragmatic weakness.

1 Bookmark
 · 
102 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a very rare autosomal recessive form of spinal muscular atrophy manifested in low birth weight, diaphragmatic palsy and distal muscular atrophy. Caused by a mutation in the IGHMBP2 gene, the disease is addressed here by reference to five Polish patients in which SMARD1 has been confirmed genetically. All presented a severe form of the disease and had evident symptoms during the second month of life; with four displaying weak cries, feeding difficulties and hypotonia from birth. Two were afflicted by severe dysfunction of the autonomic nervous system. Ultrastructural analysis of a muscle biopsy revealed progressive degeneration within the nuclei of the muscle cells and Schwann cells. Neuromuscular junctions were also defective. It proved possible to identify in our patients 6 novel IGHMBP2 mutations: three missense (c.595G>C, c.1682T>C and c.1794C>A), two nonsense (c.94C>T and c.1336C>T) and one in-frame deletion (c.1615_1623del). One nonsense mutation (c.429C>T) that had been described previously was also identified. Observation of our patients makes it clear that clinical picture is still the most important factor suggesting diagnosis of SMARD1, though further investigations concerning some of the symptoms are required. As the IGHMBP2 gene is characterized by significant heterogeneity, genetic counseling of affected families is rendered more complex. IGHMBP2 protein deficiency can lead to the degeneration of nuclei, in both muscle and Schwann cells.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 01/2013; · 2.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Children with spinal muscular atrophy with respiratory distress (SMARD1) usually present within their first year of life, with respiratory failure due to diaphragmatic paralysis and progressive distal limb weakness. We present a child with a confirmed compound heterozygous IGHMBP2 mutation c.[676G>T];[2083A>T] in whom severe sensory-motor neuropathy preceded diaphragmatic paralysis by almost 3years. Autonomic system involvement with neurogenic bladder and urine retention were found at 3years. In summary, our patient highlights the broad spectrum of phenotypes observed in SMARD1. Currently, no prediction of phenotype according to genotype is possible, suggesting that yet unknown factors cause the observed phenotypic variation. Even in the absence of obvious diaphragmatic weakness, SMARD1 should be considered in severe infantile onset neuropathies. High throughput techniques, such as next generation sequencing, will possibly offer a useful approach in the heterogeneous group of inherited neuropathies.
    Neuromuscular Disorders 12/2013; · 3.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The phenomenon of multiquantum downconversion is of great interest in quantum optics. In the limit of a classical driving field it can be described by an interaction Hamiltonian (in the interaction picture). For k=2 an interaction of this type is of interest in the context of squeezing. For multiquantum processes of higher order (k>2), however, the Hamiltonian is known to lead to a divergent dynamics. This problem is resolved by taking into account the quantization of the pump mode. More recently, the realization of similar interactions also became possible in the quantized motion of a trapped atom, where the operator it represents the annihilation of a motional quantum of the center-of-mass motion. For k=2 such a dynamic has been used to generate motional squeezing, and other interactions of that type have been considered
    01/1998;