Cleft Lip and Cleft Palate

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 Palate The palate is the structure that forms the roof of the mouth and floor of the nasal cavity. This structure is divided into soft and hard palates. Palate: Anatomy (CLP)
  • Cleft palate Palate The palate is the structure that forms the roof of the mouth and floor of the nasal cavity. This structure is divided into soft and hard palates. Palate: Anatomy (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

Epidemiology

The prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of orofacial clefts varies widely around the world. The following data are specific to the United States.

• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 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 Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency based on infant gender Gender Gender Dysphoria:
  • CL and CLP are more common in males.
  • CP is more common in females.
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency 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 Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 13 and 18 in these children
  • Ethnicity
    • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency 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 Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of OFC.
      • Infants of non-Hispanic African American mothers have a significantly lower prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of OFC.
  • Health factors: increased prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of OFC is seen in children of mothers who:
    • Smoke
    • Are diabetic
    • Are obese
    • Consume alcohol during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care

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 Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure are implicated; mutations in interferon regulatory factor 6 (IRF6) are commonly seen with nonsyndromic clefting.
  • Environmental
    • Maternal exposures
      • Alcohol consumption
      • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
      • Pre-gestational and gestational diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
      • 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 The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  • Teratogens
    • Anti-seizure medications
      • Phenytoin Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. First-Generation Anticonvulsant Drugs
      • Valproate Valproate A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of epilepsy and bipolar disorder. The mechanisms of its therapeutic actions are not well understood. It may act by increasing gamma-aminobutyric acid levels in the brain or by altering the properties of voltage-gated sodium channels. First-Generation Anticonvulsant Drugs
      • Topiramate Topiramate A sulfamate-substituted fructose analog that was originally identified as a hypoglycemic agent. It is used for the treatment of epilepsy and migraine disorders, and may also promote weight loss. Second-Generation Anticonvulsant Drugs
    • 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 Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Antimetabolite Chemotherapy
      • Retinoic acid
• 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 Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 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 Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 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 Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 22)

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

Clinical Presentation

• Cleft lip
  • Unilateral or bilateral
  • Cleft primary palate Palate The palate is the structure that forms the roof of the mouth and floor of the nasal cavity. This structure is divided into soft and hard palates. Palate: Anatomy: Cleft involves the upper lip Upper Lip Melasma and alveolus (i.e., anterior to incisive foramen).
  • CLP: involving the palate Palate The palate is the structure that forms the roof of the mouth and floor of the nasal cavity. This structure is divided into soft and hard palates. Palate: Anatomy in addition to the upper lip Upper Lip Melasma and alveolus (rarely, alveolus may be intact)
  • Severity may vary: complete (involving the nostril), incomplete, or lesser-form (e.g., micro)  
• Cleft palate Palate The palate is the structure that forms the roof of the mouth and floor of the nasal cavity. This structure is divided into soft and hard palates. Palate: Anatomy
  • Soft palate Soft palate A movable fold suspended from the posterior border of the hard palate. The uvula hangs from the middle of the lower border. Palate: Anatomy only
  • Soft palate Soft palate A movable fold suspended from the posterior border of the hard palate. The uvula hangs from the middle of the lower border. Palate: Anatomy and secondary (i.e., posterior to incisive foramen) hard palate Hard palate The anteriorly located rigid section of the palate. Palate: Anatomy
  • Submucosal: Cleft is hidden underneath a mucosal layer.

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 Palate The palate is the structure that forms the roof of the mouth and floor of the nasal cavity. This structure is divided into soft and hard palates. Palate: Anatomy may need magnetic resonance imaging (MRI) to be identified.
  • Amniocentesis Amniocentesis Percutaneous transabdominal puncture of the uterus during pregnancy to obtain amniotic fluid. It is commonly used for fetal karyotype determination in order to diagnose abnormal fetal conditions. Polyhydramnios: Prenatal diagnosis may prompt investigation for other syndromic features.
• 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 Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus with particular attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment 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. Nervous System: Anatomy, Structure, and Classification (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 Palate The palate is the structure that forms the roof of the mouth and floor of the nasal cavity. This structure is divided into soft and hard palates. Palate: Anatomy from 9–12 months followed by long-term speech therapy Speech Therapy Treatment for individuals with speech defects and disorders that involves counseling and use of various exercises and AIDS to help the development of new speech habits. Myotonic Dystrophies
• Alveolar correction may be performed at 7–9 years followed by other corrective surgeries.