Search PubMed⌕ Search

Biomedical subjects

Matthew Pitt

Publications and source records attributed to Matthew Pitt.

3 recordsLinked to original sources
PubMed2004

Clinical and neurophysiological characteristics of congenital myasthenic syndromes presenting in early infancy.

The congenital myasthenic syndromes (CMS) constitute a group of genetic disorders, which affect neuromuscular transmission, presenting usually within the first years of life and with a clinical spectrum ranging from mild muscle weakness to severe disability with life-threatening episodes. We present clinical and neurophysiological data of 11 patients (four males, seven females) with CMS diagnosed during the last 5 years. Eight of the 11 patients presented immediately after birth and the remainder by 10 months of age; eight patients had contractures at birth and seven of them required assisted ventilation either immediately in the neonatal period, or at some point afterwards due to respiratory distress or recurrent apnoeas. Neurological signs at presentation were: in nine patients profound hypotonia, in five absent tendon reflexes, in seven ptosis and in eight bulbar signs. In six patients an edrophonium test was performed: only three of them had a positive response; however, eight out of 11 patients responded at least partially at some point in their illness to pyridostigmine. Diagnosis of CMS was confirmed either by demonstration of a decrement after repetitive nerve stimulation or by increased instability and jitter after stimulated single fibre EMG. In five patients, there was a positive family history with death of at least one previous sibling with an undiagnosed neuromuscular disorder. As regards final outcome, five patients died at ages ranging from 1 to 17 months, two patients are still ventilator-dependent at 3 and 5 months of life, respectively, and four patients still survive with either a mild or a moderate motor delay (follow-up range 8-38 months). None of the clinical or neurophysiological characteristics were correlated with outcome (Fisher's exact test). We conclude that a significant number of CMS patients may present in the neonatal period with a variable clinical expression and usually with a poor prognosis. The recognition of specific clinical constellations combined with a search for aetiology at a molecular level will enable the further characterisation of subgroups of CMS.

Age of Onset↗
PubMed2003

Severe infantile neuropathy with diaphragmatic weakness and its relationship to SMARD1.

A group of 13 patients with early onset diaphragmatic palsy in association with a progressive neuropathy is presented. All eight of those tested were found to have mutations in the same gene encoding the immunoglobulin mu-binding protein 2 (IGHMBP2) in patients with spinal muscular atrophy (SMA) with respiratory distress type 1. Six out of these eight patients had either homozygous or compound heterozygous mutations, and two had only a single heterozygous mutation. Detailed analysis of the clinical picture and the neurophysiological and histopathological findings indicated that these patients shared similar characteristics, which were further developed as a set of diagnostic criteria. Some of the most striking of these were early onset of respiratory compromise, a markedly low birth weight, very slow motor nerve conduction velocities and a general decrease in the size of myelinated fibres on sural nerve biopsy. Extensive histological examination of the spinal cord in one patient failed to find any evidence of an SMA. Four out of the five not tested genetically were positive for all diagnostic criteria. None of the cases of early onset neuropathies or spinal muscular atrophies with early respiratory failure reviewed in the literature shares the exact characteristics, but many do have very close similarities. Their classification varies, but the discovery of mutations in IGHMBP2 in cases that are variously classified as SMA plus or severe infantile neuropathy with respiratory distress points to a need for the search for this genetic defect to be widened to include both groups. The fact that we identified other, similar cases of neuropathy and early respiratory failure with and without IGHMBP2 mutations suggests genetic as well as clinical heterogeneity in these infants. It is possible that infants that do not have mutations in the IGHMBP2 gene will be found to have mutations in a similar functioning gene.

Axons↗