Objective: To determine the number of primary laminin α2 gene mutations and to conduct genotype/phenotype correlation in a cohort of lamininα2-deficient congenital muscular dystrophy patients. Background: Congenital muscular dystrophies (CMD) are a heterogenous group of muscle disorders characterized by early onset muscular dystrophy and a variable involvement of the CNS. Laminin α2 deficiency has been reported in about 40 to 50% of cases of the occidental, classic type of CMD.1,2 Laminin α2 is a muscle specific isoform of laminin localized to the basal lamina of muscle fibers, where it is thought to interact with myofiber membrane receptor, such as integrins, and possibly dystrophin-associated glycoproteins.3,4Methods: Seventy-five CMD patients were tested for laminin α2 expression by immunofluorescence and immunoblot. The entire 10 kb laminin α2 coding sequence of 22 completely laminin α2-deficient patients was screened for causative mutations by reverse transcription (RT)-PCR/single strand conformational polymorphisms (SSCP) analysis and protein truncation test(PTT) analysis followed by automatic sequencing of patient cDNA. Clinical data from the laminin α2-deficient patients were collected. Results: Thirty laminin α2-negative patients were identified (40% of CMD patients tested) and 22 of them were screened for laminin α2 mutations. Clinical features of laminin α2-deficient patients were similar, with severe floppiness at birth, delay in achievement of motor milestones, and MRI findings of white matter changes with normal intelligence. Loss-of-function mutations were identified in 95% (21/22) of the patients studied. SSCP analysis detected laminin α2 gene mutations in about 50% of the mutant chromosomes; PTT successfully identified 75% of the mutations. A two base pair deletion mutation at position 2,096-2,097 bp was present in 23% of the patients analyzed. Conclusions: Our data suggest that the large majority of laminin α2-deficient patients show laminin α2 gene mutations.
Twenty-four patients with orbital-facial manifestations of neurofibromations were examined by computed tomography. Delineation of the extent of the disease, and differentiation of the disease processes (orbital tumor, osseous orbital dysplasia, plexiform neurofibromatosis, and buphthalmos) was possible.
Seventeen patients were found to have involvement of the dural venous sinuses on magnetic resonance imaging (MRI). In 7, there was tumor invasion through the dural coverings and in 10 thrombosis occurred as a result of various causes. MRI shows tumor in the sinus as a signal producing mass replacing the normal hypointensity of rapidly flowing blood. Disruption of the hypointense leaves of the enveloping dura is also well shown by MRI. Intravascular clotting, whether in the chemical state of deoxyhemoglobin or intra- or extracellular methemoglobin can be characterized by MRI operating at high field (1.5 tesla). MRI is now the non-invasive diagnostic modality of choice in evaluation of the dural venous sinuses.
