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Facial Cleft

Linh Chen, M.D.

Midline Facial Cleft of the Upper Lip

Findings:

A midline facial cleft involving the upper lip is seen.

Discussion:

Embryology

The human face forms from five facial primordia, which are derived from the neural crest. The medial part of the upper lip forms from the fusion of the medial nasal processes. The complex embryologic development of the palate occurs between the 7th and 10th menstrual week, and results from the fusion of the primary and secondary palates.(1-2) The primary palate forms by fusion of the premaxillary part of the maxilla, and becomes the anterior portion of the hard palate. It extends anteriorly from the incisive foramen and contains the four incisor tooth buds. The secondary palate forms from the fusion of the lateral palatal shelves, which originate from the maxillary or lateral palatine processes. The fusion occurs in midline from anterior to posterior. The secondary palate forms 90% of the hard palate and soft palate, and contains all the tooth buds from the canine teeth posteriorly. The junction of the primary and secondary palates is the incisive foramen.

The normal fusion of the primary and secondary palates forms a smooth arclike configuration of the alveolar ridge of the maxilla. Failure of fusion of the paired medial nasal processes with each other or with the maxillary processes will result in cleft lip with or without cleft palate(CL-P). Clefts in the anterior palate disrupt this normal line of fusion, resulting in discontinuity in the smooth, C-shape contour of the alveolar ridge at the junction between the lateral incisors and canine tooth sockets, extending posteriorly to the incisive foramen.(3-4) Much less commonly, the defect may occur between the medial and lateral incisors. A posterior cleft will disrupt the continuity of the suture between the lateral palatine processes. It may involve only the posterior soft palate or extend anteriorly into the hard palate.

Facial cleft may involve the upper lip only or may extend posteriorly to involve the alveolus (anterior hard palate), posterior hard palate, and soft palate. Clefts may be unilateral or bilateral, symmetric or asymmetric. Anterior cleft palate is often associated with alterations of the dental lamina, which is the embryonic tooth layer.(3) This can manifest as variations in the position, number, and formation of the teeth adjacent to cleft. The lateral incisors are most commonly affected, and may be deformed or absent. An isolated cleft palate is usually posterior, involving primarily the soft palate with variable extension into the hard palate. A midline cleft lip can also occur, which is often associated with underlying midline brain defects, such as holoprosencephaly. In a recent editorial Moss cautioned regarding the misuse of the term cleft lip and cleft palate. As he stated " a cleft lip is actually a cleft of the primary palate, involving the prolabium, premaxilla and the anterior hard palate anterior to the incisive foramen. The cleft palate is a cleft of the secondary palate. It is not uncommon for these terms to be confused in reports and papers. Midline cleft lip is actually a different entity altogether with significant differences in outcome (Tessier type of facial clefting). It must be appreciated that midline clefts involve increased problems such as maintaining blood sugars and hormone deficiencies."

Incidence and Etiology

Cleft lip with or without cleft palate is the most common craniofacial malformation. There is a racial predilection, with the highest prevalence in the American Indians (3.6 in 1,000), followed by Asians (1.5-2.0 in 1,000) and Caucasians (1 in 1,000) and African Americans (0.3 in 1,000).(5) In the newborns, isolated CL is more commonly unilateral (80%) and, when unilateral, it usually occurs on the left (70%). Approximately 70% of unilateral CL have associated CP, whereas bilateral CL will have associated CP in 85% of the cases. When both CL and CP are present, 75% are unilateral and 25% are bilateral. Combined CLCP (21%) were more likely than isolated CL (8%) to have associated anatomic malformations or abnormal karyotype.(6)

Isolated CP is a distinct entity separate from CL-P.(1) Siblings of patients of CL-P have an increased frequency of CL-P but not of cleft palate alone, and siblings of patients with cleft palate alone have an increased frequency of cleft palate but not of CL-P.

Incidence of Facial Cleft in Subsequent Offspring

Cleft Lip ± Palate (%)
Cleft Palate Alone (%)

Unaffected Parents

No affected offspring

0.1
0.04

No affected offspring + one affected first cousin

0.4
0.09

One affected offspring

4
2

Two affected offspring

9
1

One affected offspring + one affected relative

4
7

Affected Parents

One parent + no affected offspring

4
6

One parent + one affected offspring

10-17
15

Two parents + one affected offspring

60
60

From: Jurkiewicz MJ, Krizek TJ, Mathes SJ, Ariyan S (eds): Plastic Surgery: Principles and Practice. St. Louis, CV Mosby, 1999

Isolated CL-P without associated abnormality is considered to have multifactorial inheritance with strong familial aggregation.(7) A number of genes or loci have thought to be involved, including transforming growth factor-a and a region on chromosome 6p23-24.(8) In addition, maternal teratogens including phenytoin, valproate and methotrexate have also been implicated.

Prenatal Diagnosis

Second trimester transabdominal ultrasound has been used to diagnose CL/P. Although the structures of the face are formed by the end of first trimester, the mandible and maxilla and soft tissues of the face are not clearly visualized until second trimester. The sensitivity for detection of CL/P associated with other anomalies approaches 100%, although it is as low as 50% for isolated CL/P. (9)

Visualization of the upper lips is best achieved in the coronal plane. A vertical hypoechoic region through the fetal upper lip represents the defect in cleft lip. This finding may be corroborated by a similar defect of the soft tissues of the upper lip overlying the maxilla in the axial plane.(10)

A unilateral cleft lip (arrow) on the left side is seen

The anterior palate is best visualized in the axial plane as a continuous, smooth, echogenic, C-shaped curve of the tooth-bearing alveolar ridge of the maxilla. This can be differentiated from the inferior mandible, which has a V-shaped configuration. An anterior cleft defect is detected as a defect between the tooth sockets in the alveolar ridge of the maxilla, which is deep to the upper lip. There may also be distortion of the normal C-shaped contour. (11)

In bilateral cleft lip and palate, there is a premaxillary protrusion that is seen as a paranasal echogenic mass. The premaxillary protrusion results from instability of the facial structures during embryologic development, which produces uninhibited growth of the vomer and premaxillary bones and soft tissues. This occurs with bilateral complete left lip and palate, but not with other types of facial clefts or with cleft palate alone. (12) The paranasal echogenic mass seen sonographically is best visualized on the sagittal view. It is located inferior to the nose, with irregular contour and similar echogenicity to bone and alveolar structures. In some cases, soft tissue mass may be seen protruding outward and upward from the upper lip. Nyberg et al. suggest that presence of a paranasal echogenic mass is a better predictor of bilateral cleft lip and cleft palate than sonographic evaluation of the cleft itself, which may not be visualized. (12)

 

Two cases of bilateral cleft lip and palate. The premaxillary protrusion is seen (arrows)

Antenatal Management

Prenatal detection of or suspicion of CL-P should initiate a detailed anatomic survey of the fetus for additional anomalies, some of which are subtle and may not be detected prenatally. The most common associated abnormalities are of the limbs and spine (33%), followed by the cardiovascular system (24%). (6) Therefore, fetal echocardiography should be considered. Recently, Nyberg and coworkers reported their findings on fetal outcome in 65 fetuses with facial clefts.(13) The prevalence of assoicated anomalies increased with the severity of the clefting abnormality. Only 20% of fetuses with isolated CL had associated anatomic abnormalities, compared to 47% of fetuses with unilateral CL-CP, 55% of fetuses with bilateral CL-CP, and 100% of fetuses with midline clefts.

Facial cleft is also associated with cytogenetic anomalies. The prevalence of chromosome abnormalities differed with the type of cleft. None of the fetuses with isolated CL had an abnormal karyotype, compared to 20% of fetuses with unilateral CL-CP, 30% of fetuses with bilateral CL-CP, and 100% of fetuses with midline CL-CP.(13) The presence of other structural defects would also increase the likelihood of an underlying genetic abnormality. Fetal karyotype analysis should be considered when other anomalies are detected and/or when the cleft are known to be associated with high risk for chromosome abnormalities.

Sonographic surveillance during the remainder of the pregnancy may be helpful for detection of additional anomalies that were not previously detected or that may develop. Third trimester findings in more severe clefting defects may include polyhydramnios and small stomach, which are likely consequences of an abnormal swallowing mechanism. If termination of the pregnancy is desired, a post-mortem should be performed to search for related anomalies that may affect parental counseling in future pregnancy.

Postnatal Management

Prenatal detection of facial cleft allows appropriate counseling of the parents with respect to postnatal management. Facilitation of feeding is of utmost importance in the immediate postnatal period. Primary surgical repair of the cleft lip usually occurs at three months of age, with subsequent repair of the palate at around six months. The restoration of facial appearance and function relies on the success of the primary surgery. Again accurate characterization of the cleft permits parental counseling with regard to the degree of cosmetic deformity and surgical result.

Newborn with cleft lip and palate

Two years after repair of the cleft

 

 

Genetic Counseling

Empirical data is available regarding recurrence risks for isolate CL-P defects. (14) The risk for siblings of a proband with a CL-P, where the parents are unaffected is 4% after one affected child and 8% after two affected children. The recurrence risk if one parent and one child are affected is 17%. Risks to first-, second-, and third-degree relatives of a proband with a CL-P is 4%, 0.7%, and 0.3%, respectively.(15) The risk for siblings of individual with a cleft palate alone is 2%.

 

Fetal-Neonatal Cleft Lip and Palate

Entity
Genetics

Chromosomal Errors

Trisomy 13

Trisomy 18

Triploidy

Sporadic (unless parental translocation)

Trisomy 4p

4p deletion

Trisomy 9

5p deletion

Early amnion rupture sequence

Sporadic

Teratogenic Effects

Fetal hydantioin effect

Fetal trimethadione effect

Fetal valproate effect

Sporadic

Fetal alcohol effect

Maternal pehnylkentonuria fetal effect

Hyperthermia-induced defects

Syndromes, Sequences and Associations

Holoprosencephaly sequence

Sporadic/AD

Caudal dysplasia sequence

Sporadic

CHARGE association

?

MURCS association

Sporadic

Short-rib polydactyly syndrome

AR

Kneist dysplasia

Sporadic/AD

Meckel-Gruber syndrome

AR

Larsen syndrome

?AD, ?AR

Neu-Laxova syndrome

AR

Child syndrome

X-linked D

Roberts SC phocomelia syndrome

AR

Cleft Lip sequence

?

Oral-facial-digital syndrome

X-linked D or AD

Miller syndrome

AR

Mohr syndrome

?AR

Facial auriculovertebral sporadic

Sporadic

Frontonasal dysplasia sequence

? Sporadi c

Robinow syndrome

?

Pallister-Hall syndrome

? Sporadic

Oculodentaldigital syndrome

AD

Adams-Oliver syndrome

AD

Aese syndrome

?AR

Van de Woude syndrome

AD

Rapp-Hodgkin ectodermal dysplasia

AD

Ectodactyly-ectodermal dysplasia-clefting syndrome

?AD

Hay-Wells syndrome

AD

Popliteal pterygium syndrome

AD

AD - autosomal dominant, AR - autosomal recessive, X-linked D - x-linked dominant

From:Dimmick JE, Kalousek DK (ed): Developmental Pathology of the Embryo and Fetus, Philadelphia, JB Lippincott, 1992

 

References:

1. Melnick M: Cleft lip and cleft palate: Etiology and pathogenesis. In Kernahan DA, Rosenstein SW, Dado DV (eds): Cleft Lip and Palate. A System of Management. Baltimore, Williams &Wilkins, 1990, p 3.

2. Kernahan DA: Classification of cleft lip and palate. In Kernahan DA, R Rosenstein SW, Dado DV (eds): Cleft Lip and Palate. A System of Management. Baltimore, Williams &Wilkins, 1990, p 13.

3. Wolfe SA, Price GW, Stuzin JM, et al: Alveolar and anterior palatal cleft. In McCarthy JG (ed): Plastic Surgery: Cleft Lip and Palate and Craniofacial Anomalies. Vol. 4. Philadelphia, WB Saunders, 1990, p 2753.

4. Moore KL: The Developing Human: Clinically Oriented Embryology. 5th Ed. Philadelphia, WB Saunders, 1993, p 213.

5. Gorlin RJ, Cohen MM JR, Levin LS: Orofacial clefting syndromes: General aspects. In Gorlin RJ, Cohen MM Jr, Levin LS (eds): Syndromes of the Head and Neck. 3rd Ed. New York, Oxford University Press, 1990, p 693.

6. Milerad J, Larson o, Hagberg C, Ideberg M. Associated malformations in infants with cleft lip and palate: a prospective, population-based study. Pediatrics 100:180-186, 1997.

7. Christensen K, Mitchell LE. Familial recurrence-pattern analysis of non-syndromic isolated cleft palate - A Danish registry study. Am J Hum Genet 58:182-190, 1996.

8. Murray J. Face facts: genes, environment, and clefts. Am J Hum Genet 57: 227-232, 1995.

9. Hafner E, Steriste W, Scholler J, Schuchter K, Philipp K. Prenatal diagnosis of Fetal malformations. Prenat Diagn 17:51-58, 1997.

10. Benacerraf BR, Frigoletto FD Jr, Bieber FR. The fetal face: ultrasound examination. Radiology 153:495-497, 1984.

11. Babcook CJ, McGahan JP. Axial ultrasonographic imaging of the fetal maxilla for accurate characterization of facial clefts. J Ultrasound Med 16:619-625, 1997.

12. Nyberg DA, Mahony BS, Kramer D. Paranasal echogenic mass: Sonographic sign of bilateral complete cleft lip and palte before 20 menstrual weeks. Radiology 184:757-759, 1992.

13. Nyberg DA, Sickler GK, Hegge FN, et al: Fetal cleft lip with and without cleft palate: US classification and correlation with outcome. Radiology 195:677, 1995.

14. Curtis E, Fraser F, Warburton D. Congenital cleft lip and palate: risk figures for counseling. Am J Dis Child 102:853-857, 1961.

15. Jorde L, Carey J, White R. Medical Genetics. Mosby, St. Louis, 1995.

Moss A. Controversies in cleft lip and palate management. Ultrasound Obstet Gynecol 18:420-1, 2001

Berge SJ, Plath H, Van de Vopndel PT et al.: Fetal Cleft Lip and Palate: Sonographic Diagnosis, Chromosomal Abnormalities, Associated Anomalies and Postnatal Outcome in 70 Fetuses Ultrasound Obstet Gynecol 18:422-431, 2001

Cash C, Set P, Coleman N: The Accuracy of Antenatal Ultrasound In the Detection of Facial Clefts in a Low-Risk Screening Population Ultrasound Obstet Gynecol 18:432-436, 2001

 

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Peter W. Callen, M.D.
Professor of Radiology, Obstetrics, Gynecology and Reproductive Science
University of California Medical Center, San Francisco, California