Nostril Asymmetry A Microform of Cleft Lip and Palate? Department of Orthodontics, School of Dentistry, Showa University.

Size: px

Start display at page:

Download "Nostril Asymmetry A Microform of Cleft Lip and Palate? Department of Orthodontics, School of Dentistry, Showa University."

Sylvia Butler
5 years ago
Views:

Review J. Showa Univ. Dent. Soc. 7: 141-146, 1987 Nostril Asymmetry A Microform of Cleft Lip and Palate?

1 Review J. Showa Univ. Dent. Soc. 7: , 1987 Nostril Asymmetry A Microform of Cleft Lip and Palate? Department of Orthodontics, School of Dentistry, Showa University Tat SUO FUKUHARA In the last 20 years, studies in experimental teratology have approached the problems of cleft lip and/or cleft palate (CLP) from various directions. Laboratory studies with experimental animals have indicated that these defects can be caused by some chemical agents and X-radiation administered at critical periods during prenatal development. However, such experiments have not proven that the cause of these defects are entirely exogenic. There is no doubt that drugs, radiation and environmental pollutants can possibly cause birth defects in individual cases. Statistically, however, they do not seem to have contributed to much of an increase. On the other hand, the great advances in genetics and embryology in the past years have not brought about a noticeable decrease either. If most of the birth defects are the result of natural genetic variation, one might speculate that there are no obvious ways to eradicate them. Murakami, Nishimura and other researchers have studied this area thoroughly, using X-radiation, maternal hypoxia, trypan-blue injection, etc. Their findings show that CLP may be hereditary in man and in certain strains of experimental animals. Fraser et al. have administered standard doses of cortisone for 11 days after insemination of some specific strain (A/Jax) and have demonstrated cleft palate in 100 per cent; other crossbred groups indicated different results. This is significant evidence of the importance of genetic background. However, Larsson has stated that environmental factors can be considered to play a prominent role in the etiology of isolated cleft palate. Etoh and his collaborators have reported an induction method of CLP in cultured rat embryos by localized administration of tunicamycin (TM), they have suggested that this TM appears to primarily affect the growth of the medial nasal process which prevents its fusion with the lateral nasal process. In spite of these laboratory studies, however, through long clinical experience, we have numerous cases which strongly imply genetic etiology for human cleft lip and/or cleft palate. The most controversial questions regard the origin and manifestation of these defects in certain families where the defects appear in every generation. However, other instances present sporadic manifestation. The same is true in the data from population surveys (Table 1). The different ratios of incidence among these various populations might be explained as follows: (1) racial differences which might result in variations in the "lethal" effects of these congenital defects; (2) cultural differences in handling defective infants, as in some races where, it is believed, an infant born with any defect is put to death immediately; (3) possible population differences of gene distributions and gene expressivity; (4) environmental differences which may affect the development of the embryo. The latter two are extremely important in the clinical study of human genetics, genetic prognosis, and genetic counseling. Population surveys provide the materials for determining gene frequencies; on the other hand, data for determining expressivity of genes which may be responsible for these defects in certain given families are not yet available. 1. Genetic Relation between Cleft Lip and Cleft Palate In spite of the general agreement that cleft lip, cleft palate, uvula bifida, anencephaly, spina bifida, etc. are classified as "status dysraphicus," the genetic relations of each to the other differ in certain ways. When the proband had a cleft lip, with or without a cleft palate, the same conditions

2 Table 1 Incidence of cleft lip and/or cleft palate. Table 2 Association of types of abnormalities between propositi and their relatives. were observed in the relatives, but extremely few cases of isolate cleft palate were found, and vice versa, the difference being statistically significant (Table 2). Fogh-Andersen also states that cleft lip, with or without cleft palate, is genetically independent of isolated cleft palate: the former is a characteristic of recessive or conditioned dominant inheritance; the latter is inherited as a dominant characteristic with a low rate of manifestation. It is presumed that soft tissue anomaly may be associated with bone cleft or deformity ; on the other hand, that cleft or deformity in the bony structure is not always associated with obvious soft tissue defects. In the past series of the author's studies, the ordinary P-A cephalography did not clearly demonstrate the defects in their images, since the image of the nasal floor where the defect may exist, is almost parallel to the eye-ear plane to which the radiation is oriented. However, laminographic X-ray technique was employed to detect the possible carrier status which may be revealed in the bony structures, premaxilla, nasal septum, and nasal shelf. Figure 1 indicates unoperated nose of the cleft patients taken at random from our files. Asymmetry of the nostrils is clearly illustrated in the cleft lip, unilateral cleft lip and palate patients other than the isolated cleft palate. This implies that inner and/or outer nasal structures will be coincidentally affected in the dysjunctioning process of the lip, alveolus and palate. Figure 2 illustrates a mother of a CLP daughter and a son with spina bifida. She had plastic surgery for a deviated nose before marriage. The nostril present severe asymmetry; the right nostril is drooping than the left. The soft tissue deformity is well coordinated with the images of the nasal septum and shelves which strongly indicates the bone deformities by her P-A X-ray. In Fig. 3 the mother of the CLP daughter shows that the left nostril is drooping and the image of the nasal shelf in the X-ray implies an opened or irregularly formed nasal shelf. The upper left lateral incisor is extremely large in the mesiodistal dimension of the crown and decalcificated at the neck. Figure 4a illustrates a non-operated male whose notches in the philtrum and lip indicate an almost transitional to the cleft condition. The X-ray shows that the level of the border of the shelves is not even. Figure 4b shows a pit closed to the left nostril and a trace of the lower lip fistulas. Figure 5 is a young female orthodontic patient. The upper right lateral incisor is congenitally missing which leaves a space in the frontal segment. Occlusal X-ray endorses a congenital missing lateral incisor and an uneven level of the shelves and asymmetry in the nostrils. Careful observation on her right philtrum may implicate that a subtle but traceable line could be a "mini-cleft" such as the case in Fig. 4a.

Fig. 1. Variations of unoperated nostril contours found in the cleft patients. Fig. 2. Mother of a CLP daughter and a son with spina vifida (asymmetry : +2).

3 Fig. 1. Variations of unoperated nostril contours found in the cleft patients. Fig. 2. Mother of a CLP daughter and a son with spina vifida (asymmetry : +2). Deviation in the nasal septum and uneven shelves are illustrated in the laminographic X-ray. 2. Diagnosis of Visible and Non-visible Carrier Status of Cleft Palate There are some eccentric contours in the shape of the nostrils, philtrum, irregular formations and rotation or occasional absence of the maxillary lateral incisors. Some individuals may also show visible associated congenital defects, such as polydactyly, syndactyly, clubfoot, hernia, malformations of the ear, etc. The variations in expressivity and resulting sporadic penetrances may be due to an exogenic sensitivity characteristic of these genetic syndromes, as suggested by experiments with animals. As one may expect, CLP shows a wide range of variants in the anatomy, as well as in Fig. 3. Mother of a CLP daughter (asymmetry : +3). Deviation in the nasal septum and uneven shelves are illustrated in the laminographic X-ray. Malformation in the maxillary lateral incisor. the physiology. The laminographic X-ray technique or CT scanning reveals subtle, otherwise invisible, traces of CLP deformities which have been concealed behind a thick veil of the soft tissues.

Fig. 4a. A male with a notch in the upper lip and philtrum (Non-operated, transitional type) (Arrow head). Fig. 4b. A male with a pit in the philtrum and lower lip fistulas (Arrow head). Fig. 5.

4 Fig. 4a. A male with a notch in the upper lip and philtrum (Non-operated, transitional type) (Arrow head). Fig. 4b. A male with a pit in the philtrum and lower lip fistulas (Arrow head). Fig. 5. A young orthodontic patient with missing maxillary lateral incisor. Nostril deformity is clear and a trace of "mini-cleft" in the left philtrum (Arrow head). 3. Discussion In the study of the pathogenesis of congenital deformities, consideration must be given to the wide range of transitional and continuous variants of these defects. For example, in the genetic study of dwarfism of the maxillary lateral incisors, the congenitally missing teeth must be treated as being in the same category. Therefore, asymmetry in the nostrils should also be considered in the genealogic study, as a "forme

145 Fig. 6. A sample used in Pashayan's study. Asymmetry of the nostril contour will not be illustrated only taking the measurements of its length and the width.

5 145 Fig. 6. A sample used in Pashayan's study. Asymmetry of the nostril contour will not be illustrated only taking the measurements of its length and the width. fruste" or microform in CLP, like other characteristics : the dwarfed or congenital missing maxillary lateral incisors, lower lip fistula, incomplete notch or trace in the philtrum. These microforms may have resulted from the undergrowth of the areas at the embryological stage or indulgent activity of the gene or genes and/or through the interaction of teratogenic agents. Pashayan and Fraser concluded that nostril asymmetry is not a microform of the CLP using experimental subjects of 50 parents (25 male, and 25 female) of children with cleft lip, with or without cleft palate, and 50 subjects drawn from the hospital staff and others. Measurements of nostril length and width were taken on the photograph to the nearest 0.5 mm. The control group has longer and narrower nostrils than the experimental group but the difference is not statistically significant (Fig. 6). Pashayan states in the paper that "perhaps Fukuhara's findings resulted from a selection of cases in which a near relative had a visible microform of cleft lip." However, there would be a methodological problem that asymmetry of the nostril contour can not be evaluated by only measuring the length and width. Asymmetry of the nostril may be evaluated by comparison of the contour or form of the nostril as a whole, and may be figured by other means than simple measuring the length and width of the nostril. Mills et al. also found no appreciable difference between the frequency of asymmetrical nostrils in a control population compared to the relatives of parents with CLP. These two studies are using 50 to 100 families as samples but the incidence of the microform will be small as the CLP incidence, so that typical asymmetry cases as illustrated in the present paper will not be presented in the sample sizes. A manifestation can not be observed in all the families of the clefts, while the frequencies of other traits, incomplete notch in the philtrum as an example, will be very few in the cleft syndrome. Conclusively, however, these results can not deny the implication that nostril asymmetry would be one of the rudimentary manifestations for cleft formation especially in the unilateral cases, and Pashayan's statement concludes contrarily that nostril asymmetry has a close relation with another visible microform of the cleft syndrome. Woolf and his collaborators have stated that "in some families cleft lip with or without cleft palate, and isolated cleft palate are strongly heritable through the action of a dominant single gene, less heritable in others through the interaction of polygenes and non-genetic factors, and may appear in others a phenocopy through the action of teratogenic agents." The extent and subtlety of these transitional variations require further study upon determination of the etiology whether these were products of recessive or dominant genes affected as exogents in the prenatal environment or entirely an exogenic product since only customary morphological methods were used for the diagnosis of these congenital defects. P-A laminography will be a tool in the diagnosis of non-visible irregularities in nasopalatal bone structures presumed to be connected with congenital CLP deformities, however, the X-ray image is not very clear. It is presumed that 3-D reconstruction of C-T scanning can prove the relation between unilateral bone deformity and asymmetry nostrils in the near future. References 1) Etoh, K., Figueroa, A., Tamura, K. & Pratt, R.M.: Induction of cleft lip in cultured rat embryo by localized administration of tunicamycine. J. Embryol. Exp. Morphol., 64: 1-9, ) Fogh-Andersen, P.: Inheritance of Harelip and Cleft Palate. Copenhagen, 1943, Ejnar Munksgaards Forlag. 3) Fogh-Andersen, P.: Inheritance pattern for cleft lip and cleft palate, In: Pruzansky, S.

6 (ed.): Congenital anomalies of the face and associated structures, Springfield, 1961, Charles C. Thomas. 4) Fraser, F.C., Faubstat, T.D., & Kalter, H.: The experimental production of congenital defects with particular reference to cleft palate, Neo-natal Studies, 2: 43-58, ) Fukuhara, T. & Saito, S.: Possible carrier status of hereditary cleft palate with cleft lip: Report of cases. Bull. Tokyo Med. Dent. Univ., 10: , ) Fukuhara, T.: New method and approach to the genetics of cleft lip and cleft palate. J. Dent. Res., 44 (Part 2-Suppl.): Jan.-Feb., ) Mills, L.F., Niswander, J.D., Mazaheri, M. & Brunelle, J.A.: Minor oral and facial defects in relatives of oral cleft patients. Angle Orthod., 38: , ) Murakami, U.: Studies on mechanisms manifesting congenital anomalies. Jpn. J. Hum. Genet., 8: , ) Murakami, U., Kameyama, Y. & Nogami, H.: Skeletal malformation in the mouse fetus caused by maternal hypoxia during early stages of pregnancy. Ann. Rep. Res. Inst. Environ. Med., 14: 53-60, ) Nishimura, H., Tanimura, T. & Suzuki, M.: Effects of thailomide administered to pregnant mice upon the development of their offspring. Acta Med. Univ. Kioto, 38: , ) Niswander, J.D.: Laminographic X-ray studies in families with cleft lip and cleft palate. Arch. Oral Biol., 13: , ) Pashayan, H. & Fraser, F.C.: Nostril asymmetry not a microform of cleft lip. Cleft Palate J., 8: , ) Tolarova, M.: Microforms of cleft lip and/or cleft palate. Acta Chir. Plast. (Praha), 11: , ) Tolarova, M., Havlova, Z. & Ruzickova, J.: The distribution of characters considered to be microforms of cleft lip and/or palate in a population of normal year old subjects. Act. Chir. Plast, 9: 1-14, ) Weinberger, T.W.: Cleft microform : report of case. J. Den. Child., March-April: , ) Woolf, C.M., Woolf, R.M. & Broadbent, B.S.: Lateral incisor anomalies. Microforms of cleft lip and palate? Plast. Reconstr. Surg., 35, , (Received August 10, 1987)

Dr.ALI AL BAZZAZ PLASTIC SURGON CLEFT LIP AND PALATE

Dr.ALI AL BAZZAZ PLASTIC SURGON CLEFT LIP AND PALATE Cleft lip (cheiloschisis) and cleft palate (palatoschisis), which can also occur together as cleft lip and palate, are variations of a type of clefting