Overview
Classification
- Orofacial clefts (OFCs) can be isolated or part of a multi-organ syndrome.
- OFCs include:
- Cleft lip (CL) with or without cleft palate (CLP)
- Cleft palate (CP)
- Typical orofacial clefts can be further subdivided based on the anatomy and position of the cleft:
- Clefts anterior to the alveolus (unilateral, median, or bilateral)
- Complete and incomplete clefts
- Postalveolar clefts
Cleft lip
Image by Lecturio.
Cleft palate
Image by Lecturio.Epidemiology
The prevalence of orofacial clefts varies widely around the world. The following data are specific to the United States.
- Prevalence: Unilateral presentation is more common than bilateral.
- CL: 3.1 per 10,000 live births
- CP: 5.9 per 10,000 live births
- CLP: 5.6 per 10.000 live births
- Prevalence based on infant gender:
- CL and CLP are more common in males.
- CP is more common in females.
- Prevalence based on maternal factors:
- Age
- CL, CP, and CLP are more common in infants born to mothers aged 35 and older.
- May be due to higher prevalence of trisomy 13 Trisomy 13 Trisomy 13, or Patau syndrome, is a genetic syndrome caused by the presence of 3 copies of chromosome 13. As the 3rd most common trisomy, Patau syndrome has an incidence of 1 in 10,000 live births. Most cases of Patau syndrome are diagnosed prenatally by maternal screening and ultrasound. More than half of the pregnancies result in spontaneous abortions. Patau Syndrome (Trisomy 13) and 18 in these children
- Ethnicity
- Prevalence of OFC is similar overall between ethnicities, with 2 exceptions:
- Infants of non-Hispanic Native Americans/Alaskan Native mothers have a higher-than-average prevalence of OFC.
- Infants of non-Hispanic African American mothers have a significantly lower prevalence of OFC.
- Prevalence of OFC is similar overall between ethnicities, with 2 exceptions:
- Health factors: increased prevalence of OFC is seen in children of mothers who:
- Smoke
- Are diabetic
- Are obese
- Consume alcohol during pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care
- Age
Etiology
- Nonsyndromic clefts have multifactorial etiologies:
-
Genetics
Genetics
Genetics is the study of genes and their functions and behaviors.
Basic Terms of Genetics
- Twin studies show a genetic component to non-syndromic clefting.
- Multiple genes are implicated; mutations in interferon regulatory factor 6 (IRF6) are commonly seen with nonsyndromic clefting.
- Environmental
- Maternal exposures
- Alcohol consumption
- Smoking
- Pre-gestational and gestational diabetes
- Folate Folate Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Folate and Vitamin B12 deficiency during pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care
- Maternal exposures
- Teratogens
- Anti-seizure medications
- Phenytoin
- Valproate
- Topiramate
-
Folate
Folate
Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects.
Folate and Vitamin B12 antagonists
- Methotrexate
- Retinoic acid
- Anti-seizure medications
-
Genetics
Genetics
Genetics is the study of genes and their functions and behaviors.
Basic Terms of Genetics
- Syndromic clefts: Multiple syndromes feature CL, CP, and CLP as part of the constellation of symptoms.
- Pierre Robin sequence Pierre Robin sequence Pierre Robin sequence, also known as Pierre Robin syndrome or simply Robin sequence, is a condition in infants that is characterized by a smaller-than-normal mandible, a tongue that retracts back into the throat, and difficulty breathing. Pierre Robin Sequence
- Patau syndrome Patau syndrome Trisomy 13, or Patau syndrome, is a genetic syndrome caused by the presence of 3 copies of chromosome 13. As the 3rd most common trisomy, Patau syndrome has an incidence of 1 in 10,000 live births. Most cases of Patau syndrome are diagnosed prenatally by maternal screening and ultrasound. More than half of the pregnancies result in spontaneous abortions. Patau Syndrome (Trisomy 13) ( trisomy 13 Trisomy 13 Trisomy 13, or Patau syndrome, is a genetic syndrome caused by the presence of 3 copies of chromosome 13. As the 3rd most common trisomy, Patau syndrome has an incidence of 1 in 10,000 live births. Most cases of Patau syndrome are diagnosed prenatally by maternal screening and ultrasound. More than half of the pregnancies result in spontaneous abortions. Patau Syndrome (Trisomy 13))
- Edwards syndrome Edwards syndrome Edwards syndrome, or trisomy 18, is a genetic syndrome caused by the presence of an extra chromosome 18. The extra chromosome is either from 3 full copies of chromosome 18 or an additional segment of chromosome 18. As the 2nd most common trisomy, Edwards syndrome is seen in 1 out of every 5,500 live births. Edwards Syndrome (Trisomy 18) ( trisomy 18 Trisomy 18 Edwards syndrome, or trisomy 18, is a genetic syndrome caused by the presence of an extra chromosome 18. The extra chromosome is either from 3 full copies of chromosome 18 or an additional segment of chromosome 18. As the 2nd most common trisomy, Edwards syndrome is seen in 1 out of every 5,500 live births. Edwards Syndrome (Trisomy 18))
- DiGeorge syndrome DiGeorge syndrome DiGeorge syndrome (DGS) is a condition caused by a microdeletion at location q11.2 of chromosome 22 (thus also called 22q11.2 syndrome). There is a defective development of the third and fourth pharyngeal pouches, leading to thymic and parathyroid hypoplasia (causing T-cell immunodeficiency and hypocalcemia, respectively). DiGeorge Syndrome (partial deletion in chromosome 22)
Progression of triad of events that underlies the clinical presentation of Pierre Robin sequence Pierre Robin sequence Pierre Robin sequence, also known as Pierre Robin syndrome or simply Robin sequence, is a condition in infants that is characterized by a smaller-than-normal mandible, a tongue that retracts back into the throat, and difficulty breathing. Pierre Robin Sequence
Image by Lecturio.
Imaging finding of the oral cavity during fiberoptic intubation in cases of Pierre Robin sequence Pierre Robin sequence Pierre Robin sequence, also known as Pierre Robin syndrome or simply Robin sequence, is a condition in infants that is characterized by a smaller-than-normal mandible, a tongue that retracts back into the throat, and difficulty breathing. Pierre Robin Sequence. Cleft palate (triangle): root of the tongue Tongue The tongue, on the other hand, is a complex muscular structure that permits tasting and facilitates the process of mastication and communication. The blood supply of the tongue originates from the external carotid artery, and the innervation is through cranial nerves. Oral Cavity: Lips and Tongue (arrowhead). The tongue Tongue The tongue, on the other hand, is a complex muscular structure that permits tasting and facilitates the process of mastication and communication. The blood supply of the tongue originates from the external carotid artery, and the innervation is through cranial nerves. Oral Cavity: Lips and Tongue protruding into the nasal cavity via a cleft palate results in larynx Larynx The larynx, also commonly called the voice box, is a cylindrical space located in the neck at the level of the C3-C6 vertebrae. The major structures forming the framework of the larynx are the thyroid cartilage, cricoid cartilage, and epiglottis. The larynx serves to produce sound (phonation), conducts air to the trachea, and prevents large molecules from reaching the lungs. Larynx (not visible).
Image: “ Pierre Robin sequence Pierre Robin sequence Pierre Robin sequence, also known as Pierre Robin syndrome or simply Robin sequence, is a condition in infants that is characterized by a smaller-than-normal mandible, a tongue that retracts back into the throat, and difficulty breathing. Pierre Robin Sequence with upper airway obstruction Airway obstruction Airway obstruction is a partial or complete blockage of the airways that impedes airflow. An airway obstruction can be classified as upper, central, or lower depending on location. Lower airway obstruction (LAO) is usually a manifestation of chronic disease, such as asthma or chronic obstructive pulmonary disease (COPD). Airway Obstruction” by US National Library of Medicine. License: CC BY 4.0
22q11.2 deletion features in a 48-year-old woman.
Image: “48-year-old woman with the 22q11.2 deletion” by Department of Psychiatry, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan. License: CC BY 2.0, edited by Lecturio.
(a): The patient’s cleft palate had previous surgery.
(b): Mild dysmorphic facial features, including a low anterior hairline, swollen eyelids, malar flatness, nose Nose The nose is the human body's primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Anatomy of the Nose with a bulbous nasal tip, hypoplastic nasal alae, square and flat nasal root, small mouth, and a thin upper lip.
Patau syndrome Patau syndrome Trisomy 13, or Patau syndrome, is a genetic syndrome caused by the presence of 3 copies of chromosome 13. As the 3rd most common trisomy, Patau syndrome has an incidence of 1 in 10,000 live births. Most cases of Patau syndrome are diagnosed prenatally by maternal screening and ultrasound. More than half of the pregnancies result in spontaneous abortions. Patau Syndrome (Trisomy 13) ( trisomy 13 Trisomy 13 Trisomy 13, or Patau syndrome, is a genetic syndrome caused by the presence of 3 copies of chromosome 13. As the 3rd most common trisomy, Patau syndrome has an incidence of 1 in 10,000 live births. Most cases of Patau syndrome are diagnosed prenatally by maternal screening and ultrasound. More than half of the pregnancies result in spontaneous abortions. Patau Syndrome (Trisomy 13))
Image by Lecturio.
Edwards syndrome Edwards syndrome Edwards syndrome, or trisomy 18, is a genetic syndrome caused by the presence of an extra chromosome 18. The extra chromosome is either from 3 full copies of chromosome 18 or an additional segment of chromosome 18. As the 2nd most common trisomy, Edwards syndrome is seen in 1 out of every 5,500 live births. Edwards Syndrome (Trisomy 18) ( trisomy 18 Trisomy 18 Edwards syndrome, or trisomy 18, is a genetic syndrome caused by the presence of an extra chromosome 18. The extra chromosome is either from 3 full copies of chromosome 18 or an additional segment of chromosome 18. As the 2nd most common trisomy, Edwards syndrome is seen in 1 out of every 5,500 live births. Edwards Syndrome (Trisomy 18))
Image by Lecturio.
Pathophysiology
All clefts arise from errors in the embryological development of the face.
- CL: failure of medial and lateral nasal processes to merge maxillary process during 1st trimester
- Can be unilateral or bilateral
- May extend to the nostril
- May extend deeper and involve the alveolus
- If failure of fusion extends to palatal shelves, it results in CLP.
- CP: partial or lack of fusion only involving the palatal shelves
Development of the lip
Image by Lecturio.
Formation of the palate
Image by Lecturio.Clinical Presentation
- Cleft lip
- Unilateral or bilateral
- Cleft primary palate: Cleft involves the upper lip and alveolus (i.e., anterior to incisive foramen).
- CLP: involving the palate in addition to the upper lip and alveolus (rarely, alveolus may be intact)
- Severity may vary: complete (involving the nostril), incomplete, or lesser-form (e.g., micro)
- Cleft palate
- Soft palate only
- Soft palate and secondary (i.e., posterior to incisive foramen) hard palate Hard palate The anteriorly located rigid section of the palate. Oral Cavity: Palate
- Submucosal: Cleft is hidden underneath a mucosal layer.
Illustration of a baby with a cleft palate
Image: “Cleft palate” by Centers for Disease Control and Prevention. License: Public Domain
Six-month-old girl before going into surgery to have her unilateral complete cleft lip repaired
Image: “Child born with cleft palate at 5 months of age” by King97tut. License: Public Domain
Diagnosis and Management
Diagnosis
- Prenatal
- Ultrasound
- Cannot be done before 13–14 weeks as facial structures have not solidified sufficiently
- Cleft lip is relatively easy to identify by ultrasound.
- Cleft palate may need magnetic resonance imaging (MRI) to be identified.
- Amniocentesis: Prenatal diagnosis may prompt investigation for other syndromic features.
- Ultrasound
- Postnatal
- Clinical diagnosis: at birth, full evaluation of the infant’s suck/swallow ability to determine how to best assist oral feeding
- Full head-to-toe evaluation for comorbidities with particular attention to:
- Nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System (33% of associated anomalies)
- Cardiac system (24% of associated anomalies)
- Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics consultation
Management
- Presurgical management:
- The goal is to facilitate feeding to allow the infant to grow to age and weight required for surgical correction.
- A multidisciplinary team of healthcare providers is required.
- Feeding bottles with large-bore nipples
- Nasoalveolar molding (orthodontist)
- Lip taping or lip adhesions
- Surgical repair of cleft lip is based on the “rule of 10s”: when infant is at least 10 weeks old and weighs 10 pounds and hemoglobin has reached 10 mg/dL
- Surgical repair of cleft palate from 9–12 months followed by long-term speech therapy
- Alveolar correction may be performed at 7–9 years followed by other corrective surgeries.
References
- Tolarová MM, Cervenka J. Classification and birth prevalence of orofacial clefts. Am J Med Genet. 1998;75(2):126-137. https://pubmed.ncbi.nlm.nih.gov/9450872/
- Mai CT, Cassell CH, Meyer RE, et al. Birth defects data from population-based birth defects surveillance programs in the United States, 2007 to 2011: highlighting orofacial clefts. Birth Defects Res A Clin Mol Teratol. 2014;100(11):895-904. doi:10.1002/bdra.23329 https://pubmed.ncbi.nlm.nih.gov/25399767/
- Shkoukani MA, Chen M, Vong A. Cleft lip – a comprehensive review. Front Pediatr. 2013;1:53. Published 2013 Dec 27. doi:10.3389/fped.2013.00053 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873527/
