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.

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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.

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.