A prospective evaluation of the prevalence of submucous cleft palate in patients with isolated cleft lip versus controls.

Although there is an established relationship between cleft lip and overt cleft palate, the relationship between isolated cleft lip and submucous cleft palate has not been investigated. To test the hypothesis that patients with isolated cleft lip have a greater association with submucous cleft palate, a double-armed prospective trial was designed. A study group of 25 consecutive children presenting with an isolated cleft lip, with or without extension through the alveolus but not involving the secondary palate, was compared with a control group of 25 children with no known facial clefts. Eligible patients were examined for the presence of physical criteria associated with classic submucous cleft palate, namely, (1) bifid uvula, (2) absence of the posterior nasal spine, and (3) zona pellucida. Nasoendoscopy was subsequently performed just after induction of general anesthesia, and the findings were correlated with digital palpation of the palatal muscles. Patients who did not satisfy all three physical criteria and in whom nasoendoscopy was distinctly abnormal relative to the control group were classified as having occult submucous cleft palate. Classic submucous cleft palate was found in three study group patients (12 percent), all of whom had flattening or a midline depression of the posterior palate and musculus uvulae on nasoendoscopy and palpable diastasis of the palatal muscles under general anesthesia. An additional six study group patients (24 percent) had similar nasoendoscopic criteria and palpable diastasis of the palatal muscles; they were classified as having occult submucous cleft palate. No submucous cleft palate was identified in the control group. Seventeen patients in the study group had an alveolar cleft with a 53 percent (9 of 17) prevalence of submucous cleft palate. In the present study, classic submucous cleft palate in association with isolated cleft lip was 150 to 600 times the reported prevalence in the general population. All children with an isolated cleft lip should undergo peroral examination and speech/resonance assessment no later than the age of 3 years. Any child with an isolated cleft lip with velopharyngeal inadequacy or before an adenoidectomy should be assessed by flexible nasal endoscopy to avoid missing an occult submucous cleft palate.     

The Cronin push-back palate repair with nasal mucosal flaps: a speech evaluation

This is a retrospective study of 92 cleft palate patients who had been repaired with the Cronin push-back palate repair with nasal mucosal flaps. The patients were evaluated by a speech pathologist for intelligibility, articulation, and resonance and rated using a 5-point scale devised for this study. Readily intelligible speech was present in 78 percent. Normal articulation was present in 66 percent. Normal resonance was present in 78 percent of the total subject group. Secondary procedures were performed in 14 percent of the group. Repaired clefts of the soft palate achieved a high rate of normal intelligibility, articulation, and resonance. Repaired submucous clefts and short palates achieved the lowest percent of normal articulation and resonance. Educational placement, hearing, and type of structural deformity all appear to influence the ultimate communication outcome.     

Teratogenic effects of dosage levels and time of administration of carbamazepine, sodium valproate, and diphenylhydantoin on craniofacial development in the CD-1 mouse fetus

The objective of this investigation was to study the teratogenic effects of dosage levels and time of administration of three anticonvulsant drugs (carbamazepine [CMZ], sodium valproate [NaV], and diphenylhydantoin [DPH]) on craniofacial development in the CD-1 mouse fetus. Pregnant females were intubated on each of days 8-10, 11-13, 14-16, and 8-16 of gestation with the following dose levels for each drug: 375, 563, 938 mg/kg CMZ; 225, 338, 563 mg/kg NaV; 50, 75, 125 mg/kg DPH. Appropriate control groups were maintained for each drug. On gestation day 17, pregnant females were killed and implantation sites were recorded as live, dead, or resorbed. All live fetuses were examined for craniofacial defects. Results of examination of 1,398 fetuses indicated that CMZ, NaV, and DPH were teratogenic and embryotoxic at all dose levels. This study indicated that the observed decrease in mean fetal weight was drug-, dose-, and time-dependent. There was a drug-, dose-, and time-dependent increase observed in the number of dead fetuses, whereas the number of resorbed fetuses was observed to be only time-dependent. The observed frequencies of hydrocephalies, secondary palatal clefts, and submucous palatal clefts were significant for all three factors (drug, dose, and time) whereas the observed frequencies of hematomas and exencephalies were significant only for drug and time. Cleft lips were observed only in the highest dose level of DPH. Uterine horn distribution of defects indicated that fetuses located at the proximal end of the horns were less subject to major defects than those fetuses located at the distal end of the uterine horns. Fetuses with craniofacial hematomas were found in the proximal one-third of the uterine horn, resorbed fetuses, and fetuses with submucous palatal clefts in the middle one-third of the uterine horns and dead fetuses and fetuses with exencephalies, cleft lips, and secondary palatal clefts were localized in the distal one-third of the uterine horns. In comparing the effect of drug, dosage, and time on the development of craniofacial malformations in the CD-1 mouse fetus, CMZ was the least teratogenic and embryotoxic of the three anticonvulsant drugs employed in this study.     

Are children with clefts underweight for age at the time of primary surgery?

Children with clefts, especially those with a cleft palate, have an impaired sucking mechanism and are therefore prone to nutritional problems. This study was undertaken to determine whether children with clefts of the lip and/or palate are underweight for age at the time of primary surgery. Underweight for age was defined as being less than 80 percent of expected weight for age or below the 3rd percentile as plotted on standard percentile charts. The records of all children with clefts seen at the Red Cross Children's Hospital between 1976 and 1996 were reviewed. Of these 740 records, 100 were excluded for inadequate data (47), severe systemic syndrome (27), no operation done (22), or craniofacial cleft (4). The records of 640 children were thus included; 195 (30.5 percent) were underweight for age. By comparison, only 13.7 percent of a similar group of noncleft controls (n = 872) were underweight for age. The difference between these two groups was highly significant (p < 0.01). Factors that influenced weight at the time of primary surgery were type of cleft and age at the time of surgery. Children with cleft palate, whether associated with a cleft lip or not, were found to be more underweight for age than those with an isolated unilateral cleft lip (p = 0.008). Children who had surgery after the age of 1 year were 1.5 times more likely to be underweight for age than children who had surgery under 1 year of age (p < 0.01). Children with isolated cleft palates who were underweight for age had a tendency toward a higher fistula rate (36 percent) than those of normal weight (24 percent) (p = 0.18).     

Development of articulation before delayed hard-palate closure in children with cleft palate: a cross-sectional study

The development of articulation before surgical closure of the hard palate was compared in 75 preschool children with cleft lip and palate and 40 preschool children born without clefts. The children were aged 2 years to 5 years 11 months. The patients had significantly poorer articulation skills than the controls at each age level. Substitutions were the most frequent error, and they did not decrease with age in the patients. Fistula size and a history of speech therapy were significant factors in the articulation error scores only in 5-year-olds. No advantage in articulation proficiency was found for those who had worn a prosthesis to occlude the hard-palate defect.     

Projections and pathways of submucous neurons to the mucosa of the guinea-pig small intestine

Summary Double-labelling immunohistochemistry and retrograde transport of the carbocyanine dye, DiI, were used to establish the pathways of submucous neurons to the mucosa of the guinea-pig small intestine. Following the application of DiI to a villus, DiI-labelled nerve cell bodies were found in the submucous plexus up to 8.3 mm circumferentially and 3.8 mm longitudinally. The size of each of the four characterised classes of submucous neurons was determined and their distributions and projections mapped. Cells characterised by vasoactive intestinal polypeptide immunoreactivity accounted for 52% of DiI-labelled cells and had the longest projections. Cells characterised by neuropeptide Y (19%) or by calretinin immunoreactivity (13% of all DiI-labelled neurons) had relatively short projections and cells with substance P immunoreactivity (20%) had intermediate lengths of projection. When DiI was applied directly to the submucous plexus, filled neurons of all classes had significantly shorter projections, indicating that they must run for considerable distances in other pathways to the mucosa, probably via the non-ganglionated plexus. On average, each villus is innervated by at least 70 submucous neurons. From quantitative estimates there are 9 submucous neurons per villus. Thus, each submucous neuron is likely to supply about 8 villi. This demonstrates a high degree of convergence and divergence in the innervation of the mucosa.     

Rare facial clefts: treatment during charity missions in developing countries

During 10 charity missions in developing countries, 14 patients of a total of 374 children with cleft lip and palate deformities were treated for rare facial clefts. There were three midline clefts (Tessier no. 0 cleft, n = 1; Tessier no. 14 cleft, n = 2), four oblique facial clefts (Tessier no. 3 cleft, n = 2; Tessier no. 5 cleft, n = 2), and seven lateral facial clefts (Tessier no. 7 cleft). Surgical treatment focused on cleft repair by soft-tissue reconstruction apart from two Tessier no. 14 clefts, in which the bony gap was also closed using bone grafts from the iliac crest. The postoperative course was uneventful except for one local wound infection that was treated successfully using oral antibiotics. This article summarizes the authors' experience with the surgical management of these malformations and considers the limitations under conditions of charity missions in developing countries. Furthermore, some rare forms of cleft formation are added to the existing literature.     

Orofacial clefts and infections during pregnancy

Orofacial clefts (OFCs) are common congenital malformations of the lip, palate, or both caused by complex genetic and environmental factors. Specific antibodies against viruses influenza, rubella, cytomegalovirus, Epstein-Barr, parotitis and hepatitis B were investigated serologically in children with orofacial clefts and in their mothers. The results were compared with those obtained in control children and their mothers. Evaluation of the results and their statistical processing supports the assumption that infection during pregnancy may have occurred in the series studied induced by viruses of influenza, rubella, cytomegalovirus and possibly also by the Epstein-Barr virus. No association with the viruses of hepatitis B and parotitis was established.     

Early palatal changes in complete and incomplete cleft lip and/or palate.

Early palatal development in various complete and incomplete forms of cleft lip and/or palate (CLP) was studied from birth to 3 months of age by means of dental casts. Palatal morphology (shape) and dimensions--based on reproducible reference points--were determined in a group of 128 CLP children and 68 normal children who served as controls. Substantial normal palatal growth during the first 3 months of life was observed. Round arch forms changed into oval arch forms. Growth mainly takes place in the sagittal direction (+4 mm) (transverse: +1 mm). Palates of CLP children differed significantly dependent on the type of cleft and whether the cleft was complete or incomplete. Cleft lip and alveolus children and bilateral cleft lip and palate children had more elongated palatal arches, whereas unilateral cleft lip and palate children and cleft palate children had wider palatal arches than the control group. Incomplete clefts differed from the control group in the same direction as their complete cleft forms, though less distinctly. Preoperative orthopedics used in CLP patients does not stimulate growth. On the contrary, it even restricts growth.     

Maternal vitamin B-6 and folate status and risk of oral cleft birth defects in the Philippines

BACKGROUND: Vitamin deficiencies induce oral clefts in animal experiments, but the role of specific nutrients in human oral clefts is uncertain. METHODS: Associations between maternal vitamin B-6 and folate status and risk of nonsyndromic cleft lip, with or without cleft palate (CL/P), were examined in case-control studies at two sites in the Philippines--Negros Occidental and Davao. Cases were mothers of affected children and control mothers were those who had no children with oral clefts. RESULTS: The risk of having a CL/P-affected child increased with increasing tertile of vitamin B-6 deficiency in both Negros Occidental and Davao (odds ratios [ORs] and 95% confidence intervals [CIs] for sites combined = 1.0 [reference], OR, 2.94; 95% CI, 1.51-5.73; OR, 4.98; 95% CI, 2.56-9.67). Poor B-6 status had a stronger association with CL/P among mothers with lower versus higher plasma folate levels. Increasing tertiles of plasma folate were marginally associated with an increased risk of clefts in both sites combined (1.0 [reference]; OR, 1.58; 95% CI, 0.93-2.68; OR, 1.59; 95% CI, 0.94-2.70). Increasing tertiles of erythrocyte folate were associated with a decreased risk of CL/P in Negros Occidental (1.0 [reference]; OR, 0.34; 95% CI, 0.13-0.90; OR, 0.46; 95% CI, 0.20-1.09) and an increased risk in Davao (1.0 [reference]; OR, 1.23; 95% CI, 0.54-2.81; OR, 4.85; 95% CI, 2.24-10.50). The inconsistent associations between folate status and CL/P risk appeared to be a result of statistical interaction between folate, vitamin B-6, and case-control status that produced different results in study areas of higher versus lower prevalence of vitamin B-6 deficiency. CONCLUSIONS: Poor maternal vitamin B-6 status was consistently associated with an increased risk of CL/P at two sites in the Philippines. Folate-CL/P associations were inconsistent and may be related to the vitamin B-6 status or other characteristics of the populations under study.     

Plasma zinc concentrations of mothers and the risk of nonsyndromic oral clefts in their children: a case-control study in the Philippines

BACKGROUND: Findings from animal experiments suggest a link between poor maternal zinc status and increased risk of oral clefts in offspring; however, there are few human studies on this issue. METHODS: A case-control study was conducted using 74 case mothers of children with nonsyndromic cleft lip with or without cleft palate (CL/P, n=57) or cleft palate alone (CP, n=17), and 283 control mothers of unaffected children recruited in the Philippines in early 2003. Maternal zinc status was assessed by determining plasma zinc concentrations a mean of 5 years after delivery of the index child. Odds ratios (ORs) of estimates of the relative risk of oral clefts were calculated for quartiles of maternal plasma zinc concentrations. RESULTS: The mean plasma zinc concentration of CL/P case mothers (9.6+/-1.2, SD micromol/l) was significantly lower than that in control mothers (10.1+/-1.6 micromol/l; P<0.05). Low plasma zinc concentrations (<11.0 micromol/l) were found in 88% and 94% of CL/P and CP case mothers, respectively, and in 72% of controls (P<0.05). The ORs for CL/P and CP combined, adjusted for potential confounding factors, decreased with increasing quartile of plasma zinc as follows: 1.0 (lowest quartile reference), 0.83 (95% confidence interval 0.37-1.89), 0.70 (0.31-1.68), and 0.26 (0.10-0.70) (P trend=0.008). CONCLUSIONS: Low plasma zinc concentrations were common in Filipino women of reproductive age, and higher plasma zinc concentrations were associated with a lower risk for oral clefts in their children.     

Familial risk of oral clefts by morphological type and severity: population based cohort study of first degree relatives

Objective To estimate the relative risk of recurrence of oral cleft in first degree relatives in relation to cleft morphology.Design Population based cohort study.Setting Data from the medical birth registry of Norway linked with clinical data on virtually all cleft patients treated in Norway over a 35 year period.Participants 2.1 million children born in Norway between 1967 and 2001, 4138 of whom were treated for an oral cleft.Main outcome measure Relative risk of recurrence of isolated clefts from parent to child and between full siblings, for anatomic subgroups of clefts.Results Among first degree relatives, the relative risk of recurrence of cleft was 32 (95% confidence interval 24.6 to 40.3) for any cleft lip and 56 (37.2 to 84.8) for cleft palate only (P difference=0.02). The risk of clefts among children of affected mothers and affected fathers was similar. Risks of recurrence were also similar for parent-offspring and sibling-sibling pairs. The “crossover” risk between any cleft lip and cleft palate only was 3.0 (1.3 to 6.7). The severity of the primary case was unrelated to the risk of recurrence.Conclusions The stronger family recurrence of cleft palate only suggests a larger genetic component for cleft palate only than for any cleft lip. The weaker risk of crossover between the two types of cleft indicates relatively distinct causes. The similarity of mother-offspring, father-offspring, and sibling-sibling risks is consistent with genetic risk that works chiefly through fetal genes. Anatomical severity does not affect the recurrence risk in first degree relatives, which argues against a multifactorial threshold model of causation.     

Projections of neurons with neuromedin U-like immunoreactivity in the small intestine of the guinea-pig

Summary Neuromedin U immunoreactivity was located histochemically in the guinea-pig small intestine. Projections of immunoreactive neurons were determined by analysing patterns of degeneration following nerve lesions. The co-localization of neuromedin U immunoreactivity with immunoreactivity for substance P, neuropeptide Y, vasoactive intestinal peptide and calbindin was also investigated. Neuromedin U immunoreactivity was found in nerve cells in the myenteric and submucous plexuses and in nerve fibres in these ganglionated plexuses, around submucous arterioles and in the mucosa. Reactive fibres did not supply the muscle layers. Most reactive nerve cells in the myenteric ganglia had Dogiel type-II morphology and in many there was co-localization of calbindin, although some Dogiel type-II neuromedin U neurons were calbindin negative. Lesion studies suggest that these myenteric neurons project circumferentially to local myenteric ganglia. Projections from myenteric neurons also run anally in the myenteric plexus, while other projections extend to submucous ganglia, and still further projections run from the intestine to provide terminals in the coeliac ganglia. In the submucous ganglia neuromedin U was co-localized in three populations of nerve cells: (i) those with vasoactive intestinal peptide immunoreactivity, (ii) neurons containing neuropeptide Y, and (iii) neurons containing substance P. Each of these populations sends nerve fibres to the mucosa. Neuromedin U immunoreactivity is thus located in a variety of neurons serving different functions in the intestine and therefore probably does not have a single role in intestinal physiology.     

Oblique facial clefts: pathology, etiology, and reconstruction

Modern views on embryology have increased our understanding of the nature of oblique facial clefts. The anomalies that have their origin at the junction of facial processes, such as the nasomaxillary dysplasias, may be named primary clefts or transformation. The maxillary clefts that are due to a developmental arrest of the skeleton are in fact secondary defects of differentiation defects. The teratology of these malformations is discussed, and attention is drawn to the amniotic rupture syndrome as a possible cause. All these clefts are rare, their incidence ranging from 0.75 to 5.4 per 1000 common clefts. This author has been involved in the treatment of nine of these patients. Four had their malformation reconstructed with one of the conventional procedures described in the literature, but the results, although initially acceptable, soon deteriorated. A more aggressive approach was therefore chosen. Rotation and advancement of the cheek proved to be extremely effective and is now advocated as the procedure of choice. The transposition of a median forehead flap is considered an excellent alternative. Use of these procedures in five patients is reported. There were no complications.     

Cleft lip with and without cleft palate in blacks: an analysis of 81 patients

The clinical records of 81 black patients with cleft lip with or without cleft palate were reviewed. Four had midline clefts. Of the remaining 77, 45 were unilateral (left 28, right 17), with 11 of these involving only the primary palate. Bilateral clefts were seen in 32, with only 2 involving just the primary palate. Males and females were approximately equal in number. Two were associated with EEC syndrome. Other congenital anomalies were seen in 9 patients. The family history was positive for clefts in 5 of 65 patients (7.7 percent). A review of 255 white patients with cleft lip with or without cleft palate revealed a positive family history in 94 (37 percent). The difference was statistically significant.     

The case for early bone grafting in cleft lip and palate: a second report

In 1982, the first long-term study of our early bone-grafting and infant maxillary orthopedic approach to newborn complete clefts of the lip, alveolus, and palate was published. The protocol and sequence of procedures were shown on the first 16 consecutively treated orthodontic patients, with a mean age of 14 years. Cephalometric analysis evaluated anteroposterior and vertical facial growth. This report follows the next 37 consecutively treated individuals in a similar manner and includes not only 20 complete unilateral clefts, but also 17 complete bilateral clefts. Results, when evaluated alone and in comparison with the original series, show once again that there are no adverse growth restraints and that early primary bone grafting in our protocol leads to teeth in better overall occlusion than if it had not been undertaken.     

Inflammatory obstruction of the olfactory clefts and olfactory loss in humans: a new syndrome?

The first step in the olfactory perception is the activation by odorants of sensory neurones in the olfactory epithelium. In humans, this sensory epithelium is located at 2 narrow passages, the olfactory clefts, at the upper part of the nasal cavities. Little is known about the physiology of these clefts. We examined, in 34 patients, the impact of obstructed clefts upon detection and postlearning identification of 5 odorants. The location and extension of the obstructions were assessed using endoscopy, CT scans, and MRI. The inflammatory obstruction was usually bilateral, extending anteroposteriorly, and confined to the clefts, with no sign of obstruction or any inflammatory disease in the rest of the nasal cavities and sinuses. When tested with 5 odorants, these patients showed greatly impaired olfaction compared with a group of 73 normosmic subjects. The majority of these 34 patients had sensory deficits equivalent to that found in another group of 41 congenital anosmic patients, where inspection with MRI indicated the lack of olfactory bulbs. This study demonstrates that the olfactory clefts, in human, function as an entity that is different from other regions of the nasal cavity and is the target for local inflammatory events that are apparently not responding to corticoid and antibiotic treatments.     

Intraorganic venous bed of the stomach cardia in children during the first 3 years of life

The intraorganic venous bed of the gastric cardial part has been studied in 27 organs, obtained from children corpses of both sex beginning from birth up to three years of life. They died from causes that were not connected with gastric or vascular system pathology. The results of the investigation prove the presence of mucous, submucous, muscular and serous-subserous venous plexuses in the wall of the gastric cardial part in children of the first three years of life. Every membrane of the stomach wall has its specific structure of the venous link in the microcirculatory bed. In the stomach mucous membrane already in a newborn there are complexly built microcirculatory pathways. Age changes are mostly expressed in the venous link of the gastric mucous membrane; this is probably connected with functional activity of the given layer of the organ. The largest venous vessels are situated in the gastric submucous base. By the end of the newborn period and, especially fully, during the successive age periods immune protection of the gastric wall is formed as an accumulation of lymphoid tissue to an antigenic effect of food. In these age groups certain structural mechanisms of blood outflow from the gastric wall appear.     

Problems in using birth certificate files in the capture-recapture model to estimate the completeness of case ascertainment in a population-based birth defects registry in New York State

BACKGROUND: The limitations and underlying assumptions of the capture-recapture methods have hindered their application in epidemiological settings, especially in evaluating the completeness of birth defects registries. This study explored the possibility of using birth certificates as the secondary data source in a simple two-source capture-recapture model to estimate the completeness of case ascertainment of the Congenital Malformations Registry (CMR) for selected major birth defects. METHODS: The CMR and the birth certificates were used as the primary and secondary sources, respectively. Children who were born in 1996-2001 and had selected major birth defects were identified from the two sources. The accuracy of the diagnoses was examined by comparing the individual birth defect categories of the children from the two sources. RESULTS: Discrepancies in birth defect categories in the two data sources and false positives in the birth certificates were the major problems encountered in estimating the completeness of the CMR using the simple two-source capture-recapture method. The estimated completeness for selected major birth defects was only about 71%. Stratified analyses resulted in relatively high estimated completeness for oral clefts (90%) and Down syndrome (88%). CONCLUSIONS Although the birth certificate data was not a good source for estimating the completeness of case ascertainment of the CMR using capture-recapture methods, the analyses provided reasonable estimates for some conditions that were relatively easy to identify and diagnose at birth, such as oral clefts and Down syndrome.