Cleft Severity Research Articles

A Comparison of the Acute Toxicity, Neuropathology, and Electrophysiology of N,N-Diethyl-m-toluamide and N,N-Dimethyl-2,2-diphenylacetamide in Rats

The insect repellent DEET and the structurally related herbicide diphenamid both cause ataxia associated with a spongiform myelinopathy largely confined to the cerebellar roof nuclei. This local myelinopathy was accompanied by the formation of neuronal cytoplasmic clefts and was produced by a single dose of 1 to 3 g/kg N,N-diethyl-m-toluamide (DEET). These dose levels also produced a severe and often fatal prostration and clear electrophysiological signs of prolonged suppressed seizure activity. Diphenamid produced an identical myelinopathy after doses of 0.8 to 1.5 g/kg but without the severe prostration, suppressed seizures, or neuronal clefts. The effects of diphenamid were shown to be reversible over 3 to 7 days by neuropathological, motor, and auditory evoked response indices. Both compounds caused characteristic changes in auditory evoked response which may be useful in clinical diagnosis. Six other alkyl amides, two of which produce signs of CNS excitation, failed to produce myelinopathy at the maximum tolerated doses. Our findings show close parallels with a number of human cases of DEET poisoning and indicate that other amides, like diphenamid, also pose a potential hazard.

Cleft Palate Fistulas

A retrospective, multivariate statistical analysis of 129 consecutive nonsyndromic patients undergoing cleft palate repair was performed to document the incidence of postoperative fistulas, to determine their cause, and to review methods of surgical management. Nasal-alveolar fistulas and/or anterior palatal fistulas that were intentionally not repaired were excluded from study. Cleft palate fistulas (CPFs) occurred in 30 of 129 patients (23 percent), although nearly a half were 1 to 2 mm in size. Extent of clefting, as estimated by the Veau classification, was significantly more severe in those patients who developed cleft palate fistula. Type of palate closure also influenced the frequency of cleft palate fistula. Forty-three percent of patients undergoing Wardill-type closures developed cleft palate fistula versus 10, 22, and 0 percent for Furlow, von Langenbeck, and Dorrance style closures, respectively. The fistula rate was similar in patients with (30 percent) and without (25 percent) intravelar veloplasty. Age at palate closure did not significantly affect the rate of fistulization; however, the surgeon performing the initial closure did not have an effect. Thirty-seven percent of patients developed recurrent cleft palate fistulas following initial fistula repair. Recurrence of cleft palate fistulas was not influenced by severity of cleft or type of original palate repair. Following end-stage management, a second cleft palate fistula recurrence occurred in 25 percent of patients. Continued open discussion of results of cleft palate repair is recommended.

Data-Objective Diagnosis of Infant Cleft Lip, Alveolus, and Palate. Morphologic Data Guiding Understanding and Treatment Concepts

Maxillary plaster models of untreated infants with various cleft lip and palate forms have been studied under the Reflex Microscope. From the three- dimensional data processed by a PC, the specific dimensions of various cleft forms can be determined. Unexpected findings are that skeletal maxillary changes are present in infant velar clefts. The mid-sagittal maxillary length in particular becomes shorter with more severe clefting of the bony palate. From the morphologic point of view, Robin's sequence does not represent a specific entity, but usually a severe cleft of the hard palate. Unilateral clefts of lip, alveolus, and palate with a partial cleft lip reveal worse malformations than complete unilateral clefts. The morphologic changes recorded can be explained by a varying degree of lingual malposition. This reveals that displacements and malformations of infant cleft lip and palate are in fact secondary in nature. In correcting these secondary surface manifestations as soon as indicated by physiologic criteria one could hope for early normalization of sensation, perception, and function. Three-dimensional high-precision measurements are crucial for data-objective diagnoses, timing of therapy, choice of treatment, and in later evaluation of the results.

Concomitant developmental anomalies of the face in patients with clefts of lip (alveolus, and palate) or cleft palates.

Out of 2,829 cleft patients of Nordwestdeutsche Kieferklinik Hamburg 356 were found to have additional pathologic findings in the head and neck area. It was noted that the greater the dimension of the cleft, the greater the number of concomitant anomalies. However, the severity of the additional malformation could not be correlated to the severity of clefting. All additional pathologic findings were classified according to Pfeifer's morphogenetic classification of craniofacial anomalies. In cleft patients the region most often affected was found to be the lateral (and posterior) parts of the head. However, in unilateral clefts it was not possible to correlate the location of the cleft to the location of the concomitant malformation.

A review of tooth formation in children with cleft lip/palate

The literature on tooth formation in children with cleft lip and/or palate is reviewed. The main focus of interest is the association of cleft type and dental abnormalities in number, size, shape, timing of formation, and eruption and cause of the abnormalities. The upper lateral incisor is the most susceptible to injury in the area of cleft in both deciduous and permanent dentitions. This tooth is affected in most instances, even in the cases of microforms of the cleft lip. The prevalence of hypodontia increases strongly with the severity of cleft. More teeth are congenitally missing from the upper jaw than from the lower jaw; however, in the permanent dentition both jaws are affected. Very high prevalence of hypodontia are observed in connection with the Van der Woude syndrome associated with cleft and with the Pierre Robin anomaly. Hypodontia is similarly prevalent in subjects with isolated cleft palate with and without a positive family history of clefts. The prevalence of hypodontia varies largely in different populations. Asymmetric formation of the contralateral teeth is a milder form of hypodontia. The prevalence of asymmetrically developing pairs of teeth is far more common in children with clefts than in children with normal palates or lips. In the permanent dentition the timing of tooth formation is delayed in children from all cleft groups compared to noncleft children. The delay lengthens (with increasing severity of cleft) from 0.3 to 0.7 years and is similar in all permanent teeth in both jaws. In children with hypodontia, the delay is still more severe. As the child becomes older, the delay may increase. The size of the permanent teeth is smaller than in noncleft children and the metric asymmetry of the crown or root size is apparent in both jaws. Enamel defects and abnormalities in shape and size of both deciduous and permanent teeth are far more common in children and fetuses affected with cleft than in normal subjects. These abnormalities occur in both jaws. Dental abnormalities in number, size, shape, timing of formation, eruption, and the cleft itself seem to have a common cause in most instances. The postnatal environmental factors-nutrition, infections, and surgical treatment—may have an effect only on enamel defects and, perhaps, in some instances, on agenesis of the permanent teeth.

Analysis of upper beak defects in chicken embryos following with retinoic acid

Implanting inert carriers soaked in retinoic acid into the anterior margin of the developing limb of chicken embryos leads to orofacial malformations as well as affecting pattern formation in the limb. Using anion-exchange beads as carriers, and soaking solutions of 1-10 mg/ml retinoic acid, almost 100% of the embryos have malformations of the face. The effects on the treated limbs range from symmetrical patterns of duplicated digits (maximum number of digits being four) to truncations in which no digits were formed at all. Typically, in the malformed faces the upper beak is completely absent, no nostrils are present and the front of the face forms a scalloped rim of tissue above the mouth. By reference to normal beak development, the seven bulges of tissue that make up the rim can be identified as derivatives of the masses of tissue that normally would fuse to form the upper beak. The roof of the mouth consists of three bulges of tissue flanked by widely separated palatal shelves. The defect can thus be classified as severe bilateral clefting of the primary palate. By examining the morphology of the faces of treated embryos, the origin of the defect can be traced to failure of the frontonasal mass to enlarge. Thus, the oronasal fissures are very wide and fusion across them to form the primary palate cannot occur. The way in which retinoic acid brings about the defect is discussed in relation to possible mechanisms involved in the production of cleft palate. The parallel is noted between the associated effects of retinoic acid on beak and limb morphogenesis and the chick mutation cpp, that also affects both face and limbs.

Fetal mortality in oral cleft families (IX): factors relating to the occurrence of sporadic clefts.

Pedigree data on 854 probands with cleft lip and/or cleft palate from the State of Indiana are presented. These include 123 probands with cleft lip alone (CL), 453 with cleft lip and palate (CLP), and 278 with isolated cleft palate (CP). Probands and families were interviewed at the Indiana University Medical Center during the years 1962-1980. Among features of special interest are an excess of bilateral CLP (46% of all CLP cases) and a significantly greater number of older mothers and fathers (over 34 years old) than in the general population. An apparent increase in the proportion of sporadic cases with time may be due to bias in ascertainment. It is suggested that the increased proportions of more severe clefts and older parents are among several factors which contribute to the incidence of fetal mortality in a cleft population. The association of fetal mortality with liability to clefting introduces a more precise way to define a sporadic cleft. That is, a truly sporadic cleft is one conceived as a single occurrence event and has survived to become a liveborn cleft child whereas other apparently sporadic cleft individuals represent the surviving cleft in a sibship in which fetal mortality has eliminated all other cleft offspring already conceived. This observation has applications to the collection and interpretation of genetic pedigree data for clefts as well as many other genetic conditions.

The correction and preservation of arch form in complete clefts of the palate and alveolar ridge.

A simple but effective means of guiding the cleft alveolar ridge into good contour of the upper dental arch is presented. When apposition of the alveolar ridge is achieved, the position is stabilized with a rib graft at from 4 to 9 months of age. The palate is not repaired until the bone graft is well fixed. The contour of the alveolar ridge in severe clefts is markedly improved over that previously achieved.

Effect of palatoplasty and cleft extent on facial and dental relations

Clinical evaluation and lateral cephalometric films were made of 88 Caucasian females, in three age groups and all with isolated clefts of the palate, to evaluate the effect of palatoplasty and the extent of the cleft in the palate on facial and dental relations. From the findings in this investigation it can be concluded that modifications of the Wardill-Kilner palatoplasty necessitated by the extent of the cleft in the palate did not result in any consistently significant changes in the skeletal-facial relationships. Dentally, on the other hand, there was an increased incidence of malocclusion in the group with severe palatal clefts.

The correction and preservation of arch form in complete clefts of the palate and alveolar ridge.

MONROE, CLARENCE W. M.D.; GRIFFITH, B. HEROLD M.D.; ROSENSTEIN, SHELDON W. D.D.S.; JACOBSON, BAILEY N. D.D.S. Author Information