Jan-Hendrik Lenz

Genome-wide linkage scan of nonsyndromic orofacial clefting in 91 families of central European origin†

Orofacial clefts are among the most common of all congenital disorders. Nonsyndromic cases of cleft lip with or without cleft palate (NSCL/P) and cleft palate only (NSCPO) are considered to have a multifactorial etiology which involves both genetic and environmental factors. We present the results of a genome‐wide linkage scan in 91 families of central European descent with nonsyndromic orofacial clefts (NSC). The sample included 74 NSCL/P families, 15 NSCPO families, and 2 mixed families (a total of 217 affected and 230 unaffected individuals were genotyped). We genotyped 542 microsatellite markers (average intermarker distance = 6.9 cM). Multipoint nonparametric linkage analysis was performed using Allegro 2.0f. In addition to the factors investigated in previous genome‐wide linkage analyses, we searched for sex‐specific susceptibility loci, loci demonstrating parental imprinting and loci that are shared by NSCL/P and NSCPO. Several genomic regions likely to contain susceptibility loci for NSC were identified at the level of nominal significance. Some of these overlap with regions identified in previous studies. Suggestive evidence of linkage was obtained for the loci 4q21‐q26 and 1p31‐p21, with the chromosome 1 locus showing a male‐specific genetic effect. Our study has identified promising chromosomal regions for the identification of NSC‐associated genes, and demonstrates the importance of performing detailed statistical analyses which take into account complex genetic mechanisms such as sex‐specific effects and genomic imprinting. Further research in large patient samples is necessary to identify factors common to NSCL/P and NSCPO.

Two-stage palatoplasty, is it still a valuable treatment protocol for patients with a cleft of lip, alveolus, and palate?

INTRODUCTION Speech development is of utmost importance and requires early closure of a palatal cleft. On the other hand, it is well known that all types and timings of surgical repair of facial clefts are detrimental to maxillary growth. Nevertheless, these days one is more and more confronted with a world-wide tendency in favour of the one-in-all operation to close clefts of the lip, alveolus, and palate. Therefore, a three-centre study was performed for testing - once more - the value of two-stage palatoplasty as a means to reduce the detrimental effects of surgery on palatal growth and at the same time to also enable early speech development. MATERIAL AND METHODS Plaster casts from 85 patients have been re-evaluated. All of them had a complete unilateral cleft of lip, alveolus, and palate. They had been treated according to the old therapy protocols followed in either one of the three different cleft centres many years ago, namely in Hamburg, (Western) Germany, Iowa City, IO, USA, and Rostock, (in those days still Eastern) Germany. The impressions had been taken already in 1987 from patients being either 8 years (36 pts.) or 16 years of age (49 pts.). Three different treatment protocols had been followed for these patients in those centres in those days: The main difference was that in centres A and B the palates were closed in two stages whilst in centre C palatoplasty was performed in just one operation. RESULTS The most interesting results regarding the palatal growth were that: 1. In centre C (one-stage palatoplasty) the patients had more constricted palates. 2. In centre A (two-stage palatoplasty) the patients had least often an anterior cross-bite. DISCUSSION AND CONCLUSION It appears that it was possible to show once more that closing the palate in one stage at age 1 year or less is interfering most with maxillary growth. This study leads us to conclude that two-stage palatoplasty is still a valuable treatment protocol for patients with a complete unilateral cleft of lip, alveolus, and palate, especially as apparently good guidance of speech development can lead to satisfactory speech for cleft patients in whom the hard palate was closed at a later age.

Veloplasty Using the Wave-Line Technique Versus Classic Intravelar Veloplasty

Objective A well-known problem in primary surgery of the soft palate is its shortness and the deficit of local soft tissue. This article introduces a modification of the primary intravelar veloplasty, allowing lengthening of the soft palate, and compares this alternative technique to the classic intravelar veloplasty. Method The soft palate wave-line technique adds a wavy incision at the velar cleft margins to the intravelar veloplasty. In 24 patients with complete clefts of the palate, either the newly developed or classic technique was performed. Four years following primary surgery, speech performance and type of breathing were analyzed. Results Even in wide clefts of the soft palate, repair was easily accomplished using the wave-line technique. Complete closure of the nasal, muscular, and oral layers was achieved, and no postoperative fistula was observed. An average lengthening of the soft palate of 56% (range 24% to 83%) was observed immediately following velar repair with the wave-line technique. Speech was significantly better in the wave-line group (p < .05). Furthermore, physiological breathing was observed more often in these patients. Conclusion Primary repair of clefts of the soft palate using the wave-line technique is straightforward, safe, and easy. On the basis of the present results, this technique seems superior to the classic intravelar veloplasty.

Reconstruction of the frontal calvarian continuity in a child using a freeze- preserved autogenous bone graft

Today, extended craniofacial defects in childhood can be treated by using modern techniques of bone banking and osteosynthesis, of particular importance when the restoration needs to consider calvarial growth. This is a report of an 8-year-old boy whose right frontal bone was removed during primary multidisciplinary trauma care. The bone was stored at a tissue bank using sterilization and freeze-dried preservation. Nine months later the graft was replaced and fixed with resorbable miniplates. Postoperatively no complications were observed and the (auto)graft has taken well. There was symmetrical craniofacial growth as well as a good aesthetic result three years after reconstruction.

Blindness following severe midfacial trauma--case report and review.

PURPOSE Severe trauma of the viscerocranium or neurocranium may result in impaired visual acuity or even blindness. Case based epidemiology, pathomechanism and actual strategies in midfacial trauma for initial therapy and prevention of posttraumatic blindness are discussed. CASE AND REVIEW A 58-year old patient was treated at our Department of Oral and Maxillofacial Plastic Surgery after his central midface had been hit by a swinging steel girder. Initially he was blind on both eyes. Initial treatment started by applying 24 mg of dexamethasone and omeprazole. During the following 2 weeks, amaurosis persisted on the left eye. On the right eye complete visual acuity was regained. On the basis of data from our Department of Oral and Maxillofacial Plastic Surgery an Odds Ratio of 0.12 was calculated for the combination of blindness and midfacial trauma. Today cortisol therapy is still used. However, hypothermia, anti-Trendelenburg position, and application of mannitol seem to be more effective therapeutic strategies. Erythropoetine and progesterone are promising drugs with neuroprotective, anti-inflammatory as well as anti-oedematous effects. CONCLUSION The risk of blindness is higher than expected. Latest findings regarding the neuroprotective effects of erythropoetine or/and progesterone seem to promise a more successful treatment.