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 (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

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 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.
  • Health factors: increased prevalence of OFC is seen in children of mothers who:
    • Smoke
    • Are diabetic
    • Are obese
    • Consume alcohol during pregnancy

Etiology

• Nonsyndromic clefts have multifactorial etiologies:
  • 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 deficiency during pregnancy
  • Teratogens
    • Anti-seizure medications
      • Phenytoin
      • Valproate
      • Topiramate
    • Folate antagonists
      • Methotrexate
      • Retinoic acid
• Syndromic clefts: Multiple syndromes feature CL, CP, and CLP as part of the constellation of symptoms. 
  • Pierre Robin sequence 
  • Patau syndrome (trisomy 13) 
  • Edwards syndrome (trisomy 18) 
  • DiGeorge syndrome (partial deletion in chromosome 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: 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
  • 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 may need magnetic resonance imaging (MRI) to be identified.
  • Amniocentesis: 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 with particular attention to:
    • Nervous system (33% of associated anomalies)
    • Cardiac system (24% of associated anomalies)
  • 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.