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Craniosynostosis (occurrence: 1/2500 live births) is a result of premature fusion of cranial sutures, leading to alterations of the pattern of cranial growth, resulting in abnormal shape of the head and dysmorphic facial features. In approximately 85% of cases, the disease is isolated and nonsyndromic and mainly involves only one suture. Syndromic craniosynostoses such as Crouzon, Apert, Pfeiffer, Muenke, and Saethre-Chotzen syndromes not only affect multiple sutures, but are also associated with the presence of additional clinical symptoms, including hand and feet malformations, skeletal and cardiac defects, developmental delay, and others. The etiology of craniosynostoses may involve genetic (also somatic mosaicism and regulatory mutations) and epigenetic factors, as well as environmental factors. According to the published data, chromosomal aberrations, mostly submicroscopic ones, account for about 6.7-40% of cases of syndromic craniosynostoses presenting with premature fusion of metopic or sagittal sutures. The best characterized is the deletion or translocation of the 7p21 region containing the TWIST1 gene. The deletions of 9p22 or 11q23-qter (Jacobsen syndrome) are both associated with trigonocephaly. The genes related to the pathogenesis of the craniosynostoses itself are those encoding transcription factors, e.g., TWIST1, MSX2, EN1, and ZIC1, and proteins involved in osteogenic proliferation, differentiation, and homeostasis, such as FGFR1, FGFR2, RUNX2, POR, and many others. In this review, we present the clinical and molecular features of selected craniosynostosis syndromes, genotype-phenotype correlation, family genetic counseling, and propose the most appropriate diagnostic algorithm.

In the original article, figures 1 and 2 were inadvertently interchanged initially. The correct figures are as shown below. The original article has been corrected.

Point mutation and loss of heterozygosity (LOH) analyses were performed in 12 Polish patients with a classic symptom of NF2 - bilateral vestibular schwannomas (BVS). In 5 patients (41.7%), germline mutations were found in the NF2 gene: 2 previously reported substitutions (c.592C>T and c.52C>T) and 3 novel mutations (c.1001_1002insG, c.1029_1030insCC, c.774_778dupGAATG). In addition, LOH analysis of 30 tumour samples from 10 patients revealed a molecular basis of NF2 in 3 patients (25%) that did not have any germline mutation. The molecular defects in sporadic cases of NF2 are still being discussed.

We report a case of 43-yr-old Caucasian female with an unusual, cyclin D1 positive marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) type of the mediastinum. To date, only about 30 cases of this entity have been published. They occur mainly in Asian females with a history of coexisting autoimmune disease. To our knowledge, this is the first case of mediastinal MZL with cyclin D1 expression. In the span of 6 yr this patient's tumor recurred three times, was surgically treated, and initially diagnosed as paraganglioma. The diagnosis was based on histopathological examination only. Our final diagnosis of MZL was made by combined evaluation of histopathology (HP), immunohistochemistry (IH), flow cytometry (FCM), fluorescence in situ hybridization (FISH), and molecular biology studies. We found a positive cyclin D1 reaction by IH and cyclin D1 mRNA (CCND1) overexpression by reverse transcription polymerase chain reaction (RT-PCR). Very high cyclin D1 to beta-actin mRNA ratio in this case was comparable with the ratio, characteristic for mantle cell lymphoma (MCL). However, there was no translocation t(11;14) found by FISH and an immunophenotype by IH and FCM was consistent with MZL ruling out MCL diagnosis. In addition, our case differs from other, previously reported thymic MZL lymphoma cases by no autoimmune disease association, Caucasian origin, and the absence of the plasmacytic differentiation on both HP/IH.

Mantle cell lymphoma (MCL) is most frequently diagnosed by the routine histological (HP) and immunohistochemical (IH) examination. Herein we present a case of 47-yr-old female with general lymphadenopathy and leukemic blood picture. She was initially diagnosed with marginal zone lymphoma (MZL). This diagnosis was based not only on the HP/IH examination but also on the presence of IgM paraproteinemia. Flow cytometry (FCM) examination was helpful in making of the final diagnosis of MCL. Fluorescence in situ hybridization and cyclin D1 mRNA detection by RT-PCR additionally confirmed the MCL diagnosis. The IgM paraproteinemia is rare in MCL, although is a common feature of lymphoplasmacytoid lymphomas (LPL) and is considered a major characteristic of Waldenström's macroglobulinemia (WM).

Neural tube defects (NTDs) are a common cause of disability or death of new-borns, but the aetiology and genetic background of this disease are still poorly understood. Therefore, it was decided to determine the conditions for the identification of several polymorphisms and to perform a preliminary study on Polish NTD patients and their parents. According to the results of this study, the genetic predisposition to NTD can be correlated with the 677TT genotype in the MTHFR gene, 677CT/1298AC haplotype (the MTHFR gene), 2756G allele in the MTR gene, 66AG variant and minisatellite sequence with 5 or 10 repeats in intron 6 of the MTRR gene. The 530GG and TIVS7-2/TIVS7-2 genotypes in the T gene could also be considered as a risk factor for NTD. The analysis also revealed no correlation between neurulation disturbances and A4956G and A1186G mutations in the BRCA1 gene and the 844ins68bp in CBS gene. Although a correlation was found of some molecular markers with NTD, an additional examination should be conducted on more numerous groups to obtain statistically significant results.

Effective supplementation with folate, which prevents neural tube defect (NTD) occurrence, and high homocysteine levels in the blood of NTD children's mothers suggest that genes involved in folate and homocysteine metabolism can be involved in NTD aetiology. Genes encoding methylenetetrahydrofolate reductase (MTHFR) or methylenetetrahydrofolate dehydrogenase (MTHFD) belong to the first group. Genes encoding methionine synthase (MTR), its regulator - methionine synthase reductase (MTRR) and also cystathionine synthase (CBS) can be included in the second group. We present a current list of the folate and homocysteine metabolism genes that are known to be involved in NTD and pay special attention to primary and secondary NTD prevention.

Neural tube defects (NTD) together with cardiovascular system defects are the most common malformations in the Polish population (2.05-2.68/1000 newborns). They arise during early embryogenesis and are caused by an improper neural groove closure during the neurulation process. NTD can arise from the influence of specific environmental factors on the foetus. The genetic factor is also very important, because NTDs have multigenetic conditioning. It was suggested that genes connected with the regulation of neurulation could also be involved in NTD aetiology, especially when their deletion or modification leads to neural tube defects in the mouse model. Examples are genes from the PAX family, T (Brachyury), BRCA1 and PDGFRA genes.