Cleft lip and palate are the most common congenital malformations of the oral and maxillofacial region. Cleft lip and palate is also one of the congenital disorders of general interest in the academic field. According to statistics, the incidence rate in China was 0.1% in the 1960s. By 1986 the reported incidence was 0.18% in 1.2 million newborns in 29 provinces, municipalities and autonomous regions of China, with 2265 cases. This shows an increasing trend in incidence. For this reason, cleft lip and palate is a daunting prevention and treatment task for plastic surgery, maxillofacial surgery and related scientific research departments in China at present. It is also a major issue that deserves the common concern of the whole society and the construction of a harmonious society.
1, cleft lip and palate pathogenesis of research.
(1) Genetic factors.
Cleft lip and palate is a congenital disease with certain genetic factors. Mr. Madison of the University of Copenhagen, Denmark, first identified genetic factors in cleft lip and palate in 1942, which initially revealed the role of genetic factors in the etiology of cleft lip and palate. Current studies have proposed different models of inheritance, including the single gene model with reduced epistasis, the polygenic model and different combinations of the two. Multilocus and oligogenic models have also been proposed, but there is still no single model that explains the phenomenon of their familial aggregation. Cleft lip and palate are classified as lip cases with or without cleft palate and simple cleft palate. Genetics and human embryology suggest that the pathogenesis of cleft lip or palate with or without cleft palate and cleft palate alone are different and therefore cleft lip or palate with or without cleft palate and cleft palate alone can be discussed separately. In addition, cleft lip and palate can be divided into nonsyndromic and syndromic cases. Non-syndromic is a general term for cleft lip, cleft lip combined with cleft palate, or cleft palate alone that are not associated with other systemic organ malformations and are not part of the syndromic phenotype.
(1) Genes associated with non-syndromic cleft lip and palate
Non-syndromic cleft lip and palate can be divided into non-syndromic cleft lip with or without cleft palate and simple cleft palate. There are more academic studies on uncomplicated cleft palate, but the reported results are less consistent.
②Syndromic cleft lip and palate related genes
There are up to 300 syndromic conditions that fit Mendel’s law. Many studies have identified genes that may be involved in syndromic cleft lip and palate.
The following are currently representative and well-studied. Mutations in the interferon regulatory factor 6 gene, ectodermal dysplasia, and mutations in the TBX22 gene, among others.
(2) Environmental factors.
In any organism, during embryonic development, although the genetic factors that maintain the characteristics of the species are important, the environmental (maternal) conditions that supply the embryo growth are also important. An abnormal environment can also produce an abnormal fetus.
①The theory of impressions of pregnant women: The book “Huainanzi” written by Liu An in the early Han Dynasty (about 2nd century B.C.) in China has the saying that “the pregnancy sees a rabbit and the child lacks lips”. The book “Treatise on the Origin of Diseases” written by Sui Chao Yuanfang (610 AD) has a record that “a human being born with missing lips resembles the lips of a rabbit, so it is called a hare’s deficiency, which is caused by a woman seeing a rabbit during pregnancy and eating rabbit meat”. Physicians in Europe before the 19th century had similar views on the occurrence of lip cases and other congenital malformations. They believed that if a pregnant woman saw a hare or a lame man during pregnancy, the image of the hare or lame man could be imprinted on the embryo like a photograph, so that the fetus would be born with hare lips or deformed feet. This theory is incorrect.
Stress theory: The deformity of some children with cleft lip and palate is closely related to an unusual shock, fear or sadness of the mother in early pregnancy, i.e. the stress theory. Excessive stress of a short or long period of time in early pregnancy, although not likely to act directly on the embryo, can affect the pregnant woman’s body, altering its blood chemistry and indirectly causing changes in the fetus’ body.
③Endocrine disorders: the action of excessive adrenocortical hormones can produce congenital cleft palate malformations.
④Viral infection: In a woman who has rubella within the first 3 months of pregnancy, most of the babies she gives birth to suffer from congenital malformations of the face.
⑤ Nutritional deficiencies: vitamin deficiencies can cause malformations in embryonic growth and development.
(6) Hypoxia: Living in an environment lacking oxygen can greatly increase the incidence of malformations.
(vii) Drug and chemical poisoning: exposure to pesticides and chemicals can be one of the main causes of cleft lip and palate epidemiological investigations.
(viii) Old age and excessive childbirth: Decline in reproductive function and atrophy of reproductive organs cause congenital malformations in the fetus.
⑨ Gynecological diseases: fetuses born with endometritis and uterine fibroids sometimes have congenital malformations.
⑩Physical injury: radiation exposure can cause congenital malformations.
Other causes include immune reaction, amniotic adhesions and some mechanical causes. etc.
2.The pathogenesis of cleft lip and palate
(1) Formation of lip and palate
Formation of lip: In the 3rd week of human embryonic development, an oral cavity appears at the front of its foregut. The oral cavity at this time is the basis for the future oral and nasal cavities, so embryology calls it the primitive mouth. There is a membrane between the primitive mouth and the foregut called the oropharyngeal membrane.
By the 4th week of embryonic development, the primitive mouth is very large and polygonal in shape. There are five protrusions around the outer part of this polygonal mouth: one is the nasal frontal process, which is located in the upper center; two are the palatine process, which is on the upper sides; and two are the inferior frontal process, which occupies all of the lower part.
Soon after the formation of the two inferior frontal processes, a part of them is connected to each other in the midline, and later, they are completely connected. After the two inferior frontal processes are connected to each other, they form the lower lip, the mandible and the first 2M3 of the tongue.
Soon after the formation of the nasal frontal process, it is divided into a mid-nasal process and two lateral nasal processes at the lower end. There is a concavity between the middle nasal process and the two lateral nasal processes, which is called the nasal concavity. The nasal concavity begins to deepen in the fourth week and later becomes a nasal aperture. There is a groove between the lateral nasal eminence and the maxillary eminence, called the nasolacrimal duct.
At the 6th week of embryonic development, two small bulbous protrusions, called bulbous protrusions, are formed at the lower end of the mid-nasal process.
As the nasal frontal process grows and divides downward into two small protrusions, the maxillary process also grows and extends toward the midline. As the maxillary process extends toward the midline, it first separates the orbit from the oral cavity and later blocks the path of the lateral nasal process downward.
By the seventh week of embryonic development, the maxillary process joins the lateral nasal process above; in the midline with the glomerulus, forming the base of the nostril and all of the upper lip. Also, at this same time, the two bullets are joined in the midline to form the nasal pedicle, the middle of the labial man and the anterior jaw.
Formation of the palate: the lesser bulbous process and the maxillary process, while they are developing outside the mouth to form the external nasal region and the upper lip, they also develop inside the mouth. The lesser bulbous process is intraoral and grows from anterior to posterior to form the nasal septum of the anterior jaw. The maxillary eminence is intraoral and grows from the alveolar ridge to the midline, forming the left and right palatal eminences. However, four points should be highlighted here.
(1) The nasal septum and palatine process are still small structures at this time, and they are not yet connected in the midline.
② The nasal septum is in direct contact with the dorsum of the tongue.
(3) The palatine process is vertically attached to the sides of the tongue.
④ The whole condition is still in contact with the nasal cavity.
By the 8th week of embryonic development, the palatine process on both sides changes rapidly from its vertical form to a horizontal form. Later, at about week 8.5, they are rapidly connected to the anterior jaw to form the complete alveolar ridge.
By the ninth week of development, the palatine processes on both sides are connected first in the midline and later in the upper part with the nasal septum to form the complete hard palate. From then on, the oral cavity is completely separated from the nasal cavity.
At 12 weeks of development, the two protrusions of the soft palate are joined in the midline to form the complete soft palate. At this point, the oral cavity is completely separated from the nasopharyngeal cavity.
(2) Pathogenesis
(1) Formation of cleft lip: Generally, the so-called cleft lip refers to the more common single and bilateral cleft of the upper lip, but in fact, cleft lip also includes the less common median cleft of the lower lip, orofacial cleft, oblique cleft of the face and median cleft of the upper lip.
Lower lip median cleft The two mandibular processes below the embryonic primitive oral cavity are joined in the midline at a very early stage (around the 3rd to 4th week) to form the later 3 parts of the lower lip, mandible and anterior 2M of the tongue.
The angle of the mouth cleft (transverse facial cleft) The mandibular eminence and maxillary eminence are joined at a very early stage on both sides of the mouth to form the angle of the mouth and the cheek. If the two protrusions are not connected in part or in whole on one or both sides during this period, the fetus is born with various degrees of orofacial clefts on one or both sides. It is also called transverse facial cleft.
Facial oblique cleft The maxillary eminence and the nasofrontal eminence are connected at a very early stage on both sides of the face, forming the lateral nasal and cheek parts. If the two protrusions are not connected on one or both sides of the face during this period, the fetus is born with various degrees of facial clefts on one or both sides.
Unilateral or bilateral cleft lip The maxillary eminence and the bulbous eminence are joined on either side of the upper lip by the 7th week, forming the upper lip and alveolar eminence. A fetus born with a cleft lip of various degrees on one or both sides and a corresponding cleft of the alveolar process will be born if the two protrusions are partially or completely unconnected on one or both sides at this time.
Median cleft of the upper lip Two small bulbous prominences join each other in the midline at the same time or slightly earlier than the maxillary prominence, forming the nasal tubercle, the labial manuscript, and the forehead. A fetus born during this period with a cleft of the upper lip of various degrees on one or both sides if the two prominences are partially or completely unconnected on one or both sides. The fetus is born with various degrees of cleft of the upper midlip on one or both sides and corresponding cleft of the forehead or alveolar ridge.
② Formation of cleft palate
Unilateral or bilateral cleft palate: the two palatine processes in the oral cavity change from a vertical to a horizontal position at week 8.5, followed by a complete hard palate at week 9, when they join each other in the midline and the nasal septum above them. In the previous period, at week 8.5, the two palatine processes were on one or both sides, and some or all of them did not change from vertical to horizontal position, then the palatine processes on that side or part were not connected, and the fetus was born with various degrees of cleft palate on one or both sides.
Soft palate cleft: After the formation of the hard palate, the two protrusions that constitute the soft palate and the pendulum are joined in the midline of the pharynx at the 12th week, forming the complete soft palate and the pendulum. If some or all of these two protrusions in the pharynx are not connected during this period, the fetus will be born with various degrees of cleft palate.
2.Treatment of cleft lip and palate
The treatment of cleft lip and palate has a history of more than 1600 years. It is universally recognized that the originator of cleft lip repair was a famous Chinese doctor in the Jin Dynasty (316 AD). The traditional treatment model for cleft lip and palate was a single surgical procedure. After a long history of more than a thousand years, although surgical methods have been continuously improved and refined, the issues of ideal functional restoration, especially the restoration of phonological function, the impact of surgery on maxillofacial growth and development, as well as mental health and social behavior, are still major challenges that have not been satisfactorily resolved to date and confuse the attending.
The modern concept of cleft lip and palate treatment is not just surgical repair, but a three-dimensional treatment model including orthopedic, surgical, orthodontic, and phonological restoration of normal anatomical and physiological functions, i.e. cleft lip and palate sequence treatment.
The so-called cleft lip and palate sequence of treatment is to treat the corresponding morphological, physiological, and psychological defects of the patient from birth to adulthood, with each stage of growth and development. It also means to take the most suitable method and get the best result in the best period of treatment, in the form of programmed treatment plan.
3.Prevention.
(1) Maintain a good state of mind to welcome the new life.
(2) It is well documented that taking folic acid in the first trimester of pregnancy can significantly reduce the risk of developing cleft lip and palate.
(3) Early detection of cleft lip and palate deformities can be achieved through regular perinatal examinations.
(4) Parents-to-be should abandon bad lifestyle habits as early as possible; such as smoking, alcohol abuse ……