Craniofacial Characteristics In Parents Of Children With

Non-syndromic Cleft Lip And/or Cleft Palate

The purpose of this study was to determine whether there are differences in craniofacial morphology between parents of children with non-syndromic cleft lip and palate and normal controls with no family history of cleft in their families in a Saudi sample, that might possibly assist in devising a screening method that could identify an individual as "at-risk" in producing a child with a cleft.

Lateral cephalometric radiographs were obtained from a study group consisting of 40 males and 40 females who have children with cleft deformity, and a control group of 32 males and 35 females who have no family history of clefts. A total of 10 landmarks were digitized for each individual by a custom-made computer program.

Cleft lip and palate (CL/P) is the most common oralfacial congenital deformity. This malfor- mation has intrigued a wide range of professionals in trying to expand their understanding of its etiology. Over the years, numerous etiological possibilities have been considered.¹

Warkany et al² reported that as early as 1757, Trew recognized that heredity played a role in the production of CL/P. Insight into the etiology of non-syndromic CL/P, as well as identifying individuals at high risk, may perhaps pave the way for preventive programs.

Fraser and Pashayan³ have advanced the hypothesis that if facial shape is genetically determined and also related to predisposition to the cleft lip and palate anomaly, then the parents of children with CL/P should have facial dimensions different from those of the normal population. Based on this hypothesis, the present study investigated and analyzed cranio- facial structures in a group of Saudi parents who have CL/P children and compared them to a control group with no history of clefts in the family.

The material for this study consisted of a study group and control group. The study group included 80 parents of 49 cleft children (probands) with non-syndromic cleft lip and/or cleft palate, referred from the University Hospital and the College of Dentistry, King Saud University. The control group consisted of 32 adult males and 35 adult females, with no family history of oro-facial cleft. All participants in this study are Saudi nationals. Age range, mean and standard distribution for experimental and control groups are shown in Table 1.

Lateral cephalograms were taken for each subject in both the experimental and control group using standard cephalometric machine with the following setting: MA 10, 10 seconds, KV 85, film size 8x10. The subject was asked to sit upright and the head was stabilized by the cephalostat and oriented with the Frankfurt horizontal plane, parallel to the floor. Nineteen landmarks were selected from each cephalogram (Table 2). These landmarks were modified   after   Nakasima   and   Ichinose⁴ and Rakosi⁵(Fig. 1). In case of two shadows of a landmark, the mid-point was selected. The landmarks were digitized using a numonic digitizer with 0.010 level of accuracy. Linear and angular measurements were then calculated by "PCDIC" program Version 5, being the program

Gl, glabella; Op opistocranion; N, nasion; R, intersection of UN line and cranium outline; Po, porion; Or, orbitale; Ptm, pterygomaxillary fissure; Ba, basion; Ans, anterior nasal spine; Pns, posterior nasal spine; A, subspinale, B, supramentale; Pg, pogonion; Gn, gnathion; M, menton; Go, gonion; Ar, articulare used for digitizing two-dimensional images and licensed by Dental Technology and Biomaterial Karolinska Institute, Sweden. In addition, method error due to landmark location was evaluated using Dahlbergs Equation⁶ on the data of 15 radiographs randomly selected and re-digitized. This program requests the user to register each image twice when the difference during the second registration is greater than the tolerance level of 0.5. Under such condition, an additional registration of the landmark is required. Descriptive statistical analysis which consisted of minimum, maxi- mum, mean and standard deviation was carried out. The differences between study and control group were tested using unpaired student "t" test. Stepwise logistic regression⁷ was then used to select a set of variables that discriminated between the study and control parents. These analyses were performed using the Statistical Package for Social Sciences Version 6.
   

Mean, standard deviation, mean difference of linear and angular cephalometric variables for the study and the control males are presented in Table 3. Fathers with cleft children showed a significantly shorter mandible corpus length (p < 0.01) and a shorter palate (p < 0.05) compared to the control group. The findings also revealed that the cranial base angle was more obtuse in fathers of cleft lip and palate children (p < 0.05). The Y-axis was greater (p < 0.05), the gonial angle and the mandibular plane angle were also significantly increased (p < 0.001, p < 0.01 respect- ively) in the same group of fathers (Fig. 2).

For the mothers, the discrepancy analysis for both groups are shown in Table 4. The results revealed that the mothers of cleft lip and palate children differ from the control by having an increased total anterior facial height (p < 0.05) and    lower    anterior   facial height (p<0.01).

The mandible corpus length and the mid-facial length were significantly shorter (p < 0.05) compared to unaffected mothers. The SNA angle was smaller (p < 0.05) and Y-axis was greater (p < 0.05) in mothers with cleft lip and palate children. The gonial angle and mandi- bular plane angle were greater (p < 0.001) in the same group of mothers (Fig. 3). All other differences in the measurements were not statistically significant for both fathers' or mothers' cleft lip and palate children compared to the control subjects.


Logistic Regression Analysis

A step-wise regression analysis was performed on 22 variables (Table 5) of the lateral skull radiographs for 72 cases, representing both the study and the control groups of the fathers. This was to determine which of the variables could best explain the difference between the two groups in the craniofacial characteristics. Among the twenty-two variables, the regression model selected the following variables: increased gonial angle, increased lower posterior facial heights, Y-axis angle and the mandibular length. The addition of more variables gradually increased the efficiency of the regression model, but in much smaller increment, which did not add any significant effect to the model. Consequently, as the model was applied, affected fathers (82.5%) were correctly classified with a sensitivity of 71.8%, i.e., the percent of individuals who are correctly classified as belonging to the experi- mental group. The specificity was 75%, i.e., the percent of individuals correctly classified as belonging to the control group. The same analysis was applied on data obtained from the mothers. An overall correct classification regar- ding affected mothers reached up to 75% with a sensitivity of 70% and a specificity of 77.14%. The model indicated that an increased gonial angle and a reduced SNA were the only varia- bles to differentiate the two groups (Table 6).
 

For many years, researchers have been developing methods to identify individuals at high risk to various diseases. Identified indi- viduals are then subjected to special programs such as prevention or early detection.⁸

From the literature review, there appears to be several studies which have investigated the craniofacial characteristics of parents with a child born with cleft lip or palate.³⁹¹³ These studies suggest that the parents of children with cleft lip and palate might have some morphological features different from the rest of the population. Therefore, this study was carried out to test the hypothesis that Saudi parents with cleft lip and/or palate children have different features from the normal Saudi parents, and to compare the findings of other investigators.

The overall results of the present study appear to support the tested hypothesis. From the lateral cephalometric measurements, it appears
that both sexes of the experimental group demonstrated significant findings compared to the control group. Findings common to both fathers and mothers of children with cleft lip and palate revealed an increased gonial angle, an increased mandibular plane angle and a shorter mandibular corpus length. This was asso- ciated with a backward and downward incli- nation of the mandible, thus increasing the lower facial height and increasing the Y-axis angle. An increase in lower facial height was also found in the studies carried out by some authors,³⁴ whereas others⁹¹⁰reported a dec- rease in lower facial height. Whereas, in the present study, the increased lower facial height was found to be statistically highly significant for mothers only (p > 0.01).

The increased gonial angle and short mandible observed in the present study was reported also by Raghavan et al,¹³⁴  whereas Nakasima and Ichinose did not observe a significant difference in the gonial angle. The decreased mandibular length was also in contrast to the findings reached by Coccaro et al.⁹

The mothers of the cleft lip and palate showed a significant retrusion in the linear measure- ment of point "A." This was indicated by a significantly smaller SNA angle compared to the control group. The fathers of cleft lip and palate children, despite having a significantly smaller palatal length (p < 0.05), did not show a signi- ficant decrease of the SNA angle when com- pared to the control group. This finding may be attributed to the fact that SN line and palatal plane were in a relatively retruded position. Another possible explanation could be that in the male, the shorter anterior cranial base (N-S) probably resulted in a deficient downward and forward growth of the maxilla.

The logistic regression analysis provided the authors with a model that identified certain facial characters that may help differentiate and explain the variations between the two groups. Still, a major practical difficulty is the require- ment of large sample sizes in order to achieve definitive results.
 

The parents of children having cleft lip and/or palate anomaly differed from the control group in the following aspects: