Description 

  • congenital malformation of the upper lip and/or oral cavity disrupting normal facial structure and oromotor function

Definitions 

  • World Health Organization definitions from the International Perinatal Database of Typical Oral Clefts (IPDTOC)
    • cleft lip and palate: congenital malformation with partial or complete clefting of upper lip and alveolar ridge and/or hard palate, not including the oral cleft palate of holoprosencephaly
    • cleft lip: congenital malformation with partial or complete clefting of upper lip, not including median cleft lip (holoprosencephaly)
    • cleft palate: congenital malformation with closure defect of hard and/or soft palate behind foramen incisivum without cleft lip (excluding submucous cleft palate, occult cleft palate, and cleft uvula)
    • Pierre Robin sequence: cleft palate associated with significant micrognathia, with or without retroposition of the tongue (glossoptosis) or respiratory distress

Types 

  • cleft lip with or without cleft palate
    • appears to develop from malformation of fetal primary palate with or without secondary palate malformation
    • 68% to 86% of cleft lip cases associated with cleft palate
    • other genetic anomalies (syndromic) in 14% to 30% of cases
    • subtypes include
      • microform cleft (dehiscence of orbicularis muscle with vermilion notching but intact overlying skin)
      • cleft lip and alveolus
      • incomplete unilateral cleft lip and palate (less severe congenital scar, notch in vermillion border, or partial clefting)
      • complete unilateral cleft lip and palate
      • complete bilateral cleft lip and palate
  • cleft palate alone (lip not affected)
  • appears to develop from malformation of fetal secondary palate 
  • can range from submucous clefting to complete bilateral clefting through maxillary alveolus
  • other genetic anomalies (syndromic) in 42% to 54% of cases

Who is most affected 

  • cleft palate alone twice as common in female infants 
  • cleft lip with or without cleft palate more common in male infants and usually more severe than in female infants

Incidence/prevalence

  • 1 in 700 live births overall report to have orofacial clefting (cleft lip and/or palate)
  • reported prevalence for orofacial clefts varies worldwide
    • 1.3 to 25.3 per 10,000 live births for cleft palate alone
    • 3.4 to 22.9 per 10,000 live births for cleft lip, with or without cleft palate

Likely risk factors 

Parental exposures: 

  • maternal factors 
    • history of fever 
    • cold without a fever 
    • history of skin disease 
    • maternal passive smoking 
    • maternal negative life events
    • maternal use of antipyretics or analgesics 
    • anti-infectious drugs 
    • antiepileptics
  • maternal occupational exposure to
    • organic solvents 
    • heavy metals
    • pesticides 
  • paternal factors associated with increased risk for 
    • orofacial clefting
    • paternal alcohol consumption
    • paternal smoking
  • other factors
    • pregestational hypertension
    • lower parental education level 
    • maternal Western diet 
    • low myo-inositol level in mother or child
    • low red blood cell zinc concentration in child 

Hereditary risk factors 

  • family history of first-degree relative with oral cleft MTHFR C677T polymorphism with TT genotype