Subtelomeric rearrangements in Polish subjects with intellectual disability and dysmorphic features.

Fluorescent in situ hybridization (FISH) was performed in 76 patients referred to our department because of intellectual disability and dysmorphic features that can be related to subtelomeric microaberrations. In all the patients, conventional cytogenetic methods revealed normal karyotype. Four (5.3%) subtelomeric rearrangements were detected by FISH: 2 subtelomeric 1p36 deletions, an unbalanced translocation involving chromosomes 1 and 12 with 1p36 deletion, and a de novo balanced translocation involving chromosomes 19 and 22. Thus, 3 cases of 1p36 subtelomeric deletion were found (3.95%). To confirm subtelomeric rearrangements in 2 patients, comparative genomic hybridization (CGH) was applied. Moreover, 3 cases of polymorphism without phenotypic effects were found: in 2 patients, the polymorphism involved the long arm of chromosome 2 (maternal derivative in both patients), while in the third patient, a polymorphism of the long arm of chromosome 7 was diagnosed. The latter polymorphism was also found in the patient's mother and grandfather.

Mild Smith-Lemli-Opitz syndrome: further delineation of 5 Polish cases and review of the literature.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder caused by reduced activity of 7-dehydrocholesterol reductase, resulting in an increased concentrations of 7-dehydrocholesterol and 8-dehydrocholesterol in body fluids and tissues. Phenotypically it is characterized by wide range of abnormalities, from mild to lethal forms what causes difficulties in its clinical diagnostics. To further delineate the physical spectrum of the mild form of Smith-Lemli-Opitz syndrome, especially with regard to genotype-phenotype correlation, we describe 5 Polish patients with mild phenotype (one with novel mutation in DHCR7 gene and four published before) and analyze 18 other cases from the literature. As the conclusion we give recommendation for tests toward SLOS in cases with "idiopathic" intellectual impairment and/or behavioral anomalies, as well as in biochemically doubtful but clinically fitting cases with overall gestalt and history of this syndrome.

Fibular aplasia with ectrodactyly--broadening the clinical spectrum.

Fibular aplasia-ectrodactyly is a rare disorder of the central axis, characterized by shortening of the affected limbs and formation of split hand and/or foot. Here we report on a severely affected case of fibular aplasia with ectrodactyly, in which the upper limb malformations are more pronounced than usually described in sporadic cases.

Congenital anomalies and developmental delay in a boy with double chromosome 6 derived supernumerary marker.

The frequency of small supernumerary marker chromosomes has been estimated to approximately 0.45 per 1000 newborns. They are usually seen as single marker chromosomes in a mosaic state. Two cytogenetically identical markers have been observed only occasionally. We report on a boy, with congenital heart defect, neonatal hypotonia, hypogenitalism, delayed psychomotor development and mild dysmorphic facial features. The GTG karyotype performed on peripheral blood lymphocytes revealed a mosaic male karyotype with three cell lines. One cell line had a normal karyotype. In the other two either single or double chromosome 6 derived supernumerary markers were present, leading to partial trisomy or partial tetrasomy of chromosome 6, respectively.

Thrombocytopenia-absent radius (tar) syndrome: a case with agenesis of corpus callosum, hypoplasia of cerebellar vermis and horseshoe kidney.

The thrombocytopenia-absent radius (TAR) syndrome (MIM 274000) is a congenital malformation syndrome characterised by bilateral absence of the radii with present thumbs, hypomegakaryocytic thrombocytopenia and a number of additional features including skeletal and cardiac anomalies. Mental retardation, reported in about 7% of patients, is usually secondary to intracranial hemorrhage. In 1994 there was a single report of a girl with TAR syndrome and hypoplasia of the cerebellar vermis and corpus callosum and in 2003 another case of TAR syndrome with cerebellar dysgenesis has been reported. In 2000 there was first report of horseshoe kidney in association with TAR syndrome followed by a clinical study of 34 cases with TAR syndrome in 2002 where horseshoe kidney was noted in two cases. Here we report of a girl with TAR syndrome, severe mental retardation, agenesis of corpus callosum, hypoplasia of cerebellar vermis and horseshoe kidney. There is no previous report of a child with TAR syndrome and all those associated anomalies in the same patient.

Wiedemann-Rautenstrauch (neonatal progeroid) syndrome: new case with normal telomere length in skin fibroblasts.

Wiedemann-Rautenstrauch (neonatal progeroid) syndrome is an autosomal recessive condition with characteristic appearance of premature aging present at birth (aged face, natal teeth, and wrinkled skin). Other features of the syndrome are generalized lipoatrophy with specific fat accumulation in the lateral suprabuttock region, hypotrichosis, macrocephaly (pseudohydrocephalus), and mental retardation. We report on a new case that demonstrates all typical features of the syndrome. The girl is now 16 years and 10 months old and has had follow-up from birth. We measured terminal restriction fragment (TRF) length to evaluate whether the patient's premature aging process is accompanied by shortening of telomere length in her cultured fibroblasts. Mean TRF of 13.5 kb found in our patient's fibroblasts is not shortened as compared to that of normal fibroblasts. Our results differ from those observed in Hutchinson-Gilford progeria.

Increase in the incidence of type 1 diabetes mellitus in children in three cities in Poland, 1987-1999.

The aim of this study was to evaluate the trends in the incidence of type 1 diabetes mellitus (DM) in children aged 0-14 years between 1987 and 1999 in three cities in Poland. The study area comprised the provinces of Cracow and Wroclaw and the city of Warsaw. The data were collected prospectively on the basis of the register within the framework of the EURODIAB study up till 1997 and then within the project of the Ministry of Health. During the 13 years of the study period, 766 children (380 girls, 386 boys) with newly diagnosed type 1 DM were identified. The overall age-standardized incidence rates were 8.4/100,000 standardized population/year (95% CI 7.4-9.3) for Cracow province, 6.5/100,000/year (95% CI 5.6-7.4) for Wroclaw province and 7.9/100,000/year (95% CI 6.9-8.8) for Warsaw. A significant trend of increase for children aged 0-14 years was found in the three cities. The analysis of the trend in age subgroups showed a significant increase in incidence in all three age subgroups in Warsaw and Cracow province (0-4 year-old children, p <0.05; 5-9 year-olds, p <0.001 in Cracow province, p <0.05 in Warsaw, and in 10-14 year-olds, p <0.05 in Cracow province, p <0.005 in Warsaw). In the Wroclaw province a significant increase was observed in children aged 0-4 years (p <0.05) and 5-9 years (p <0.001). In children aged 10-14 years the increase was not statistically significant. The results of our study showed that the incidence of type 1 DM in children is rising. A similar phenomenon is occurring in many other countries. The greatest increase of incidence was observed in the 5-9 year-old subgroup of children in Cracow and Wroclaw provinces and in children aged 10-14 years in Warsaw. The incidence rates in excess of 9.0/100,000 per year observed since 1996 have placed Poland in the group of countries with low to medium incidence.

Proteus syndrome: a case with clonal chromosome aberration.

Proteus syndrome is a disorder characterized by overgrowth of multiple tissues, connective tissue nevi, epidermal nevi and hyperostoses with asymmetric involvement. The clinical expression of the disorder is extremely variable. Molecular pathogenesis of the syndrome is unknown but it is hypothesized that it resulted from a somatic alteration of a gene leading to mosaic effects that would be lethal if the mutation was carried in nonmosaic fashion, and this may explain the variability among patients. We report a new case who presented at birth with asymmetric hypertrophy of the bones and soft tissues of fingers and a tumor of the chest. Cytogenetic analysis of the excised tumor revealed clonal chromosome aberration: mos46, XY, add(9)(p13) [5]/46,XY[30]. During follow up tumors of the rectum and urinary bladder were diagnosed.

The influence of vitamin E on rheological parameters in high altitude mountaineers.

Vitamin E is a fat-soluble antioxidant which plays an important role in maintaining cells in a reduced state. Oxidation reactions can lead to damage of both endothelial cells and circulating blood cells and may thus influence the rheological conditions. A group of 13 mountaineers was selected as a model for persons at increased risk of oxidative stress. 6 subjects received 200 mg vitamin E twice daily for 4 weeks, and 7 subjects received placebo. Erythrocyte filterability, blood viscosity, changes in the blood picture, and three blood coagulation factors (antithrombin III, protein C, and fibrin monomers) were investigated. The baseline values (t1) were determined at 1.500 m, and after supplementation the investigations were repeated twice at 4.300 m (t2 und t3). There was a marked rise in the hematocrit in both groups during the ascent which was due to an increase not only of the erythrocytes but also of the leucocytes. This change was more pronounced in the control group. The erythrocyte filterability was unaltered in the vitamin E group in comparison with baseline but was significantly impaired in the control group. The changes in these two parameters-hematocrit and filterability--resulted in a significant higher blood viscosity. Furthermore in the control group, but not in the vitamin E group, a significant fall in the protein C activity was observed. The cause may be an additional release from degenerated leucocytes of various proteases which degrade protein C. A further possible cause is a derangement of metabolic reactions in the vascular endothelium. All these possible causes could be counteracted by the higher antioxidative potential of the verum group.(ABSTRACT TRUNCATED AT 250 WORDS)

Disorganisation: a case with popliteal pterygia and placental-skin appendages.

We report a girl with congenital anomalies which include amniotic rings and scars, cleft lip and palate, thumb abnormalities, hexadactyly of feet, severe flexion deformities of legs and unusual finger-like appendages which were attached to the placenta. We suggest this patient represents another example of human homologue for the mouse mutant disorganisation (Ds).

[Marker chromosomes as a product of familial translocation (11;22) identified with molecular cytogenetic methods]. / Marker chromosomowy jako produkt rodzinnej translockacji (11;22) rozpoznanej metodami cytogenetyki molekularnej.

A reciprocal constitutive 11;22 translocation is the most frequent, non Robertsonian translocation in man. We describe a case of partial trisomy 11q and 22q in a child with facial dysmorphy, hypotonia, heart failure, cryptorchism and psychomotor retardation. A marker chromosome was found in this child. Chromosome analysis with the fluorescence in situ hybridization, FISH technique showed that this marker chromosome was the product of 3:1 mejotic segregation of maternal (11;22) balanced translocation. Routine cytogenetic problems with identification of marker chromosomes can now successfully be solved with the FISH technique. The presented case clearly demonstrates the diagnostic usefulness of this newest method of cytogenetic analysis.