Severe classical congenital muscular dystrophy and merosin expression

Vajsar J, Chitayat D, Becker LE, Ho M, Ben-Zeev B, Jay V. Severe classical congenital muscular dystrophy and merosin expression. Clin Genet 1998: 54: 193–198. 0 Munksgaard, 1998
It has been suggested that patients with autosomal recessive merosin deficient congenital muscular dystrophy (CMD), as opposed to the merosin positive cases form a homogeneous subgroup of a clinically more severe form of CMD. We examined merosin expression in muscle biopsies from five children with the severe classical form of CMD. Merosin deficiency was found only in 1 patient, a 6–year-old female, with abnormal brain myelination. However, her initial biopsy did not reveal the classical picture of dystrophy. The four merosin positive cases exhibited severe muscle weakness but their brain imagings were normal. There were no familial cases, except for the mother of 1 patient who had a milder form of the disease, suggesting an autosomal dominant mode of inheritance.
In contrast to previous reports, the merosin deficient CMD cases were rare in our group. Furthermore, merosin positive cases were also associated with severe phenotype suggesting that a severe phenotype is not exclusive to merosin deficient cases. Finally, the absence of merosin in a neonate with hypotonia and weakness can be helpful in making a definitive diagnosis of CMD, even though the dystrophic process may not be evident yet and histology may be non-specific.     

MYCN AMPLIFICATION IN MEDULLOBLASTOMA

Prominent neuronal differentiation and MYCN amplification occur only in a small percentage of medulloblastomas (primitive neuroectodermal tumor of the cerebellum). In this article, we describe two medulloblastomas that showed a striking degree of neuronal differentiation with islands of mature neurons associated with abundant neuropil. In these differentiated foci, there were no mitoses or atypia, and the histology was reminiscent of a malformative or hamartomatous lesion. Both tumors were assessed for MYCN amplification by the novel technique of differential polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH). In case 1, MYCN amplification was in the 10 - fold range determined by differential PCR, while in case 2 the level of amplification was marked, with 20 - 30 copies compared with diploid controls. FISH analysis also confirmed the presence of MYCN amplification in both tumors. These two cases are of great interest, especially as they show MYCN amplification in medulloblastomas with marked degree of neuronal differentiation. Furthermore, in both cases, there was evidence of a slower and more indolent clinical course, suggesting a more favorable outcome in medulloblastoma with this degree of neuronal differentiation.     

An exploration of relative health stock in advanced cancer patients.

OBJECTIVE: The authors sought to empirically test whether relative health stock, a measure of patients' sense of loss in their health due to illness, influences the treatment decisions of patients facing life-threatening conditions. Specifically, they estimated the effect of relative health stock on advanced cancer patients' decisions to participate in phase I clinical trials. METHOD: A multicenter study was conducted to survey 328 advanced cancer patients who were offered the opportunity to participate in phase I trials. The authors asked patients to estimate the probabilities of therapeutic benefits and toxicity, their relative health stock, risk preference, and the importance of quality of life. RESULTS: Controlling for health-related quality of life, an increase in relative health stock by 10 percentage points reduced the odds of choosing to participate in a phase I trial by 16% (odds ratio = 0.84, 95% confidence interval = 0.72, 0.97). CONCLUSION: Relative health stock affects advanced cancer patients' treatment decisions.     

UNUSUAL CEREBELLAR GANGLIOGLIOMA WITH MARKED CYTOLOGIC ATYPIA

Neuronal differentiation is well documented in cerebellar primitive neuroectodermal tumors but is uncommon in other cerebellar neoplasms. Although rare, gangliogliomas and gangliocytomas have been previously described in the cerebellum. We report a cerebellar ganglioglioma in a 14-year-old boy, which revealed bizzare markedly pleomorphic cells with extremely pronounced nuclear atypia but less than one mitosis per 50 high-power fields and no necrosis. The tumor showed glial as well as neuronal differentiation, with abundant bi- and multinucleated ganglion cells. There were abundant Rosenthal fibers, eosinophilic granular bodies, focal calcification, and perivascular lymphocytic infiltrates. There has been no evidence of tumor recurrence or neurological deterioration 21 years after surgery, although the marked nuclear atypia led to an initial diagnosis of an anaplastic glioma. We stress the need for careful evaluation of cerebellar gliomas in children that show only nuclear atypia or endothelial hyperplasia in the absence of other features of malignancy.     

Terminal deletion of the long arm of chromosome 3 [46,XX,del(3)(q27→qter)]

We report on a terminal deletion of the long arm of chromosome 3 [46,XX,del(3)(q27→qter)] in a female newborn infant who died 45 hours after delivery and had multiple congenital abnormalities including bilateral anophthalmia, congenital heart disease, and abnormal genitalia. The findings are compared to those of four previously reported cases with terminal del (3q). © 1996 Wiley-Liss, Inc.     

Inclusion body myositis with abundant ring fibers

Summary A 37-year-old male presenting with a 7-year history of leg weakness was found to have moderate weakness confined to the quadriceps and myopathic changes on electromyography. Serum creatine phosphokinase was 2130 units/liter. Biopsy of the quadriceps muscle revealed an inflammatory myopathy with cytoplasmic and nuclear filamentous inclusions characteristic of inclusion body myositis. An unusual finding was the large proportion of ring fibers along with severe atrophy and fibrosis. The pathogenesis of the ring fibers in this setting is discussed.