Comprehensive Genetic Evaluation of Bulgarian Children with Syndromic Craniosynostosis.

Syndromic craniosynostosis (SC) is a genetically determined premature closure of one or more of the cranial sutures, which may result in severe dysmorphism, increased intracranial pressure along with many other clinical manifestations. The considerable risk of complications along with their significant incidence makes these cranial deformations an important medical problem. Aiming to elucidate the complex genetic etiology of syndromic craniosynostosis, we investigated 39 children, screened systematically with a combination of conventional cytogenetic analysis, multiplex ligation-dependent probe amplification (MLPA) and array-based comparative genomic hybridisation (aCGH). Pathological findings were established in 15.3% (6/39) of the cases using aCGH, in 7.7% (3/39) using MLPA and 2.5% (1/39) using conventional karyotyping. About 12.8% (5/39) of the patients with normal karyotype carried submicroscopic chromosomal rearrangements. Duplications were found to be more common than deletions. Conclusion: The systematic genetic evaluation of children with SC revealed a high prevalence of submicrosopic chromosomal rearrangements (most commonly duplications). This suggests the leading role of those defects in the pathogenesis of syndromic craniosynostosis. The genetic complexity of SC was reaffirmed by the dis Bulgaria covery of pathological findings in various chromosomal regions. Certain genes were discussed in conjunction with craniosynostosis.

[Morphologically qnd immunohistochemically based screening criteria for selection of patients with possible mutation of BRCA1 gene in primary ovarian cancer].

UNLABELLED: SUMMARY AND AIM: Breast cancer (BC) and Ovarian cancer (OC) are some of the most common cancers affecting women. Environmental factors and genetic alterations are involved in the etiology of both cancers. The main susceptibility genes that predisposed to BC and OC are BRCA1 (BReast CAncer 1) and BRCA 2 (BReast CAncer 2). Those of BC and OC which are due to germline mutation in BRCA 1/2 are defined as hereditary. Because of the expensiveness of genetic testing for mutations in BRCA1 we aimed to select patients with ovarian cancer suitable for genetic testing, on the base of certain morphological and immunohistochemical criteria. MATERIAL AND METHODS: We have conducted a retrospective analysis of 29 cases with serous papillary OC, taken from the archives of the Department of Clinical Pathology, University Hospital "Dr. G. Stranski" Pleven. We performed morphological assessment and subsequent immunohistochemical study with antibodies against p53, anti BRCA1 and anti proliferative marker Ki-67. RESULTS: Nineteen (65.52%) of all 29 cases were found with loss of immunohistochemical expression of BRCA1 and we defined them as suitable for genetic testing of BRCA1 mutations. CONCLUSION: A set of morphological and immunohistochemical criteria allows screening of women that should be referred for genetic testing, as it is expensive, and the incidence of BRCA1 mutations in the general population is very low.

[Lung metastases from tumors at different sites]. / Metastazi v belite drobove ot tumori s razlichna lokalizatsiia.

A comparative study of necropsy material is carried out for the period of 1974-1983. For these ten years 11603 autopsies are performed. In 222 cases neoplastic processes with different lung metastases are obligatory, which makes 1.8% of total number of cases. The primary sites of these metastases are as follows: tumor of the stomach (26), breast (33), bile duct (10), bile ways (3), liver (13), large intestine (30), incretory glands (31), etc. The morphological evolution shows that the histologic type of the primary tumors varies (carcinomas, malignant lymphomas, teratocarcinomas, sarcomas, neuroblastomas, etc.). In some cases (carcinomas of the kidneys and liver, sarcomas of the bones) the histologic type of the primary tumor is identical to that of the Metastatic processes in the lungs. In some of the lung metastases however there are differences in the histological structure compared to the primary tumors. A clinical morphological comparative study is performed.

[Clinical difficulties and errors in making a diagnosis of chronic papillo-odditis]. / Klinichni trudnosti i greshki pri postaviane na diagnozata khronichen papiloodit.

138 patients with chronic papillooditis were investigated, 15 of them in a stage of decompensation. In 83.3% of the cases, the diagnosis was not clinically determined (including 68 of 92 endoscoped before their hospitalization--82.9%). 34 patients were diagnosed as having chronic gastroduodenitis, 15--ulcer, 42--chronic cholecystitis, 11--chronic pancreatitis, 4--cholangitis, 9--postcholecystectomic status. All these diseases developed simultaneously with the papillitis. In a second endoscopic check-up with an examination of papilla Vateri, the patients were in all the cases diagnosed without difficulties and the diagnose was confirmed by biopsy. In 21 patients there was confirmed primary papillooditis and in 127--accompanying disorders: chr. gastroduodenitis--29, chr. atrophic gastritis--18, ulcer--15, chr. cholecystitis--42, postcholecystectomic status--9, choledocholithiasis--14, chr. pancreatitis--11. Most often misdiagnosis occurs if: 1) during the routine endoscopic investigation the endoscopist does not examine papilla of Vater; 2) chr. papillitis exists simultaneously with one of the already mentioned diseases that are easier of approach for diagnostics and explanation of the disorders; 3) the clinical picture of papillitis cannot be differentiated from the one of the basic or accompanying disease; 4) the bile drainage is not prevented; 5) the result of the venous biligraphy does not lead to the diagnosis and ERCP is carried out only in a case of a clinical suspicion.