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Objective Transforming growth factor-beta (TGF-β) type 1 receptor (also known as activin receptor-like kinase 5, ALK5) is expressed in palatal tissue during embryogenesis. Experimental studies in transgenic mice with a genetic deletion of Alk5 showed that TGF-β type 1 receptor is required for upper lip and midline fusion of the hard and soft palate. In humans, association of TGF-β type 1 receptor gene ( TGFBR1 ) and the development of non-syndromic cleft lip with or without cleft palate (NSCL/P) had been observed in a multiethnic sample of Chinese, Philippine, Indian and Turkish families. In order to re-evaluate the relevance of these findings, we carried out a family-based association study among 218 NSCL/P families of Central European descent. Methods Genomic DNA was obtained from peripheral blood of 218 complete parent–offspring triads with NSCL/P. The sample comprised 14 patients with cleft lip only (CLO) and 204 patients with cleft lip and palate (CLP). Genotyping and transmission disequilibrium test (TDT) were performed on all 218 triads with a total of 17 tagging single-nucleotide polymorphisms (SNPs). We also performed testing for extended haplotypes and a log-linear model by Weinberg was used to screen parent-of-origin effects. Furthermore the use of estimates for the relative risks (RR) of Weinberg's model was obtained. Results TDT analysis revealed no significant transmission distortion, neither at the level of individual markers nor at the level of haplotypes. Similarly negative results were obtained when we restricted our analysis to the subgroup of patients with CLP ( n = 204). Relative risk calculations (RR) of the children's and mothers’ genotypes obtained negative results, after correction of p -values for multiple testing. Likewise application of Weinberg's log-linear model did not find any evidence for parent-of-origin effects in our sample. Conclusion Despite the ample evidence supporting the role of TGF-β type 1 receptor as a critically important and widespread morphogenetic regulator of craniofacial development in murine models, our results do not support TGFBR1 as major risk factor for NSCL/P in patients of Central European descent.

Summary Aim Due to the limited therapeutic options, the management of previously pre-treated recurrent head and neck carcinomas remains a challenging problem. The use of hyper-fractionated-accelerated interstitial high-dose-rate brachytherapy (HDR-BT) might be able to improve safety and survival after surgical resection. Material and methods From 2000 to 2006, 13 patients with pre-treated, recurrent head and neck cancer (oral, maxillary sinus, lips) were treated in a curative approach by resection the recurrent tumour and HDR-BT. The concept included coverage of the surgical defect and sealing of the brachytherapy applicators with free microvascular or myocutaneous flaps. Conventional radiotherapy and chemotherapy were added as required. The patient group was re-examined with respect to survival and outcome. Additionally 5 patients, who received this combination therapy for primary carcinomas were included in this report observation in order to evaluate the rate of complications and adverse effects. Results Kaplan–Meier-curves revealed a 2-year overall survival of 65.3%. The mean survival for recurrent carcinomas was 22.8 months. Patients treated for primary carcinoma had a mean survival of 34.5 months. Four out of five (80%) patients with primary head and neck cancer were alive and without evidence of disease 2 years after treatment. The acute and chronic adverse side effects were manageable. There were no relevant complications concerning tissue transfer. Conclusions Surgical resection combined with HDR-BT can lead to long-lasting remissions. A simultaneous microvascular defect reconstruction provides tissue cover for brachytherapy.