A gene for Meckel syndrome maps to chromosome 11q13.

Meckel syndrome (MKS) is a rare autosomal recessive lethal condition of unknown origin, characterized by (i) an occipital meningo-encephalocele with (ii) enlarged kidneys, with multicystic dysplasia and fibrotic changes in the portal area of the liver and with ductal proliferation, and (iii) postaxial polydactyly. A gene responsible for MKS in Finland has been mapped to chromosome 17q21-q24. Studying a subset of Middle Eastern and northern African MKS families, we have recently excluded the chromosome 17 region and have suggested a genetic heterogeneity. In the present study, we report on the mapping of a second MKS locus (MKS2) to chromosome 11q13, by homozygosity mapping in seven families that do not show linkage to chromosome 17q21-q24 (maximum LOD score 4.41 at recombination fraction .01). Most interestingly, the affected fetuses of southern Tunisian ancestry shared a particular haplotype at loci D11S911 and D11S906, suggesting that a founder effect is involved. Our observation gives support to the clinical and genetic heterogeneity of MKS.

Fetal hydrocephalus. Clinical significance of associated anomalies and genetic counseling: a pathological approach.

We report on a consecutive series of 94 cases of fetal hydrocephalus. Pathological and neuropathological findings have been thoroughly analysed in order to define more precisely the clinical significance of associated anomalies and their implications in genetic counseling. In 90.5% of cases, hydrocephalus was associated with other central nervous system (84%) or extra neural (56%) anomalies. True aqueductal stenosis occurred only twice in our series. In only 9 fetuses, hydrocephalus was an isolated finding, secondary to haemorrhage or infection. Since fetal hydrocephalus is an etiologically heterogeneous disorder, its recurrence varies greatly. Without a final diagnosis, based on well documented pathological data and cytogenetic studies, accurate genetic counseling and prenatal diagnosis in subsequent pregnancies would be impossible.

Infantile familial encephalopathy with cerebral calcifications and leukodystrophy.

Two sets of siblings, in two different families, presenting with congenital and progressive neurological disorders, cerebral calcifications and leukodystrophy are reported. In the first family, the diagnosis of brain calcifications in two infants was based on skull X-rays; in the second family, ultrasound scans showed hyperechoic areas in the basal ganglia and periventricular white matter in both infants. Neuropathological studies confirmed the calcifications and revealed severe abnormalities of the white matter with GFAP positive gliosis. Electron micrographs showed large astrocytes with an increased amount of glial filaments. In the group of idiopathic non arteriosclerotic cerebral calcifications, these four cases may represent a separate entity with possible autosomal recessive inheritance.

Cytologic features of cerebrospinal fluid in Lyme disease.

The cytomorphologic findings in the cerebrospinal fluid (CSF) of four patients with lymphocytic meningoradiculitis (Lyme disease) related to a tick bite (due in at least two cases to Borrelia burgdorferi) are reported. In all cases, the May-Grünwald-Giemsa-stained centrifuge preparations of the CSF showed a cellular pattern consisting of a lymphocytic pleocytosis composed mainly of immunoblasts and plasma cells associated with numerous foamy macrophages. Direct immunofluorescence studies in one case showed the polyclonal pattern of the immunoblasts and the plasma cells. These CSF findings can be considered as suggestive of the spirochetal origin of a lymphocytic meningitis following a tick bite.

Symptomatic xanthogranuloma of the choroid plexus of the third ventricle. A new case with ultrastructural study.

The clinicopathological findings in a new case of a surgically removed, symptomatic xanthogranuloma of the third ventricle are reported. Ultrastructural study showed that the lining epithelium of the tumor was composed of typical leptomeningeal cells, and that transitional forms from leptomeningeal cells into xanthomatous cells were present in the underlying fibrous capsule. These findings support the hypothesis of a leptomeningeal origin of the foamy cells in the present case. The ten cases reported previously of symptomatic xanthogranuloma of the third ventricle are reviewed. We suggest that xanthogranulomas of the choroid plexus might represent a heterogenous entity arising from xanthomatous changes involving various types of cells.

Cardiovascular abnormalities in thoracopagus twins: embryological interpretation and review.

The cardiovascular abnormalities of two sets of thoracopagus twins with conjoined heart and liver are described and compared with 27 well documented cases. An embryological interpretation of the cardiovascular abnormalities is suggested. The common heart in both sets showed a common atrium and two ventricles. In case 1 the great arteries were L. malposed in twin A. In case 2 the great arteries originated from their respective double outlet single ventricle. The systemic and pulmonary veins drained directly into the common atrium in case 1 and indirectly via systemic veins in case 2. The type of cardiovascular abnormalities are complex and discordent from one set to another and in the same set. However among 27 published cases of thoracopagus twins, cardiac union, including atrial union with separate ventricles, or atrial and ventricular union, was encountered in 16 cases. Approximately 90% of them are not suitable for surgical separation because of the high degree of cardiac union and the complexity of cardiovascular abnormalities. Surgical separation could be attempted in only two cases, but at the cost of the life of one of the twins.

Post-operative intracranial foreign body granuloma: a case report.

The authors report and discuss some clinical, radiological, histological and ultrastructural aspects of an intracranial foreign body granuloma. This granuloma, which simulated a cavernoma, was due to a surgical swab forgotten during a previous neurosurgical evacuation of an intracerebral hematoma.

Coincidence of familial systemic lupus erythematosus and the fragile X syndrome.

The coincidence of fragile X syndrome (fra(X] and systemic lupus erythematosus (SLE) in the same family is reported here for the first time. A 16-year-old boy with typical fra(X) had a severe SLE with multiple organ involvement. His 12-year-old sister of normal intelligence had circulating antinuclear antibodies and proliferative glomerulonephritis. The fra(X) was not found in her karyotype. Except for abnormalities due to immunosuppressive treatment during pregnancy, the association of SLE and chromosome abnormalities has been only reported in Klinefelter's syndrome. The possible pathogenic role of sex hormonal abnormalities due to an extra X chromosome has been suggested in the occurrence of SLE.

Phenotype-karyotype correlations in dup(18q): report of a case and review.

We report on a case of dup(18q) due to de novo translocation 46,XX,-21,t(18;21)(18qter----cen----21qter). The patient had many characteristic signs of full trisomy 18 except for internal organ malformations and early death. We review the phenotype-karyotype correlations between full trisomy 18 and dup(18q) and discuss the possibility of the existence of "critical zone(s)" at the proximal or/and distal region of 18q responsible for most signs of trisomy 18, such as congenital heart defect and early death.