Classification, Epidemiology, and Genetics of Orofacial Clefts

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Key points

  • The following terminology is used when describing orofacial clefts (OFCs): cleft lip alone without cleft palate (CL); cleft lip with or without cleft palate (CL/P), which includes cleft lip only and cleft lip with cleft palate; cleft lip with cleft palate (CLP); posterior cleft palate without cleft lip (CPO); syndromic and nonsyndromic; and familial and nonfamilial (or simplex).

  • Prevalence is the suggested measure of disease frequency.

  • The source population, the time period of data collection,

Historical perspective: terminology and classification

There is considerable ambiguity in the use of terminology when referring to orofacial clefts (OFCs). Many clinicians incorrectly refer to OFCs as deformities, which are said to be the result of disrupted embryologic development. In 1982, an international working group proposed our currently used concepts and terms to describe errors of morphogenesis, which include OFCs.1 The term malformation should be used for a “morphologic defect of an organ, part of an organ, or larger region of the body

Classification

Several different classification systems for OFCs have been proposed in the surgical and dental literature. These systems are primarily divided into anatomic systems useful for surgeons and embryology-based systems useful for genetic counseling and research. The disciplines of surgery, genetic counseling, and research require and use different types of OFC data, which has hindered the development of a universally acceptable and useable classification system.12

Modern concepts of classification

Incidence Versus Prevalence

Incidence and prevalence are traditional epidemiologic measures used to quantify the occurrence of disease in a population. Incidence reflects the transition from health to disease where prevalence reflects both the presence of disease as well as how long a person lives with the disease.46 Incidence is defined as the number of new cases of disease in a population of individuals at risk for developing the disease in a given time period. This measure can be expressed as either a proportion, with

Sex, Race, and Ethnicity

Prevalence of OFCs differs by sex, race, and maternal age. The prevalence of CL/P among males is approximately twice that of females, whereas the prevalence for CPO is about two-thirds that of females.55, 56

The prevalence of all OFCs is less for non-Hispanic blacks compared with non-Hispanic whites.57 African Americans are 44% less likely to have CL/P compared with non-Hispanic whites. Moreover, the prevalence of CPO was approximately 30% less for African American and Hispanic children when

Pierre Robin sequence

The Robin sequence (commonly referred to as the Pierre Robin Syndrome [PRS]) deserves special mention. Current concepts classify this as a malformation complex or a sequence, in recognition of the embryologic sequence of events involved.1 PRS is usually defined by the triad of micrognathia/retrognathia,147 cleft palate (usually U shaped but may be V shaped), and glossoptosis (abnormal posterior placement of the tongue); but there is a significant precedent for using this term to refer to only

Patient evaluation and family counseling

Most parents who have a child with an OFC wonder why this happened to their child and whether they caused it by doing something they should not have done or by not doing something that they should have done. Parents may also be worried about their chance of having the same or more severe malformations affect future pregnancies. Patients with OFCs may have similar concerns about the health of their offspring. Health professionals who care for patients with OFCs should be alert to their patients'

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References (162)

  • A. Correa et al.

    Diabetes mellitus and birth defects

    Am J Obstet Gynecol

    (2008)
  • J.K. Muraskas et al.

    Amniotic band syndrome with significant orofacial clefts and disruptions and distortions of craniofacial structures

    J Pediatr Surg

    (2003)
  • L.A. Croen et al.

    Racial and ethnic variations in the prevalence of orofacial clefts in California, 1983-1992

    Am J Med Genet

    (1998)
  • I. Emanuel et al.

    The further epidemiological differentiation of cleft lip and palate: a population study of clefts in King Country, Washington, 1856-1965

    Teratology

    (1973)
  • R.J. Shprintzen et al.

    Anomalies associated with cleft lip, cleft palate, or both

    Am J Med Genet

    (1985)
  • B.R. Rollnick et al.

    Genetic services at a center for craniofacial anomalies

    Cleft Palate J

    (1981)
  • M.C. Jones

    Etiology of facial clefts: prospective evaluation of 428 patients

    Cleft Palate J

    (1988)
  • C. Stoll et al.

    Associated malformations in cases with oral clefts

    Cleft Palate Craniofac J

    (2000)
  • E. Calzolari et al.

    Epidemiology of cleft palate in Europe: implications for genetic research

    Cleft Palate Craniofac J

    (2004)
  • E. Calzolari et al.

    Associated anomalies in multi-malformed infants with cleft lip and palate: an epidemiologic study of nearly 6 million births in 23 EUROCAT registries

    Am J Med Genet A

    (2007)
  • W. Maarse et al.

    A systematic review of associated structural and chromosomal defects in oral clefts: when is prenatal genetic analysis indicated?

    J Med Genet

    (2012)
  • M.P. Mooney

    Classification of orofacial clefting

  • D.A. Kernahan et al.

    A new classification for cleft lip and cleft palate

    Plast Reconstr Surg Transplant Bull

    (1958)
  • C.S. Harkins et al.

    A classification of cleft lip and cleft palate

    Plast Reconstr Surg Transplant Bull

    (1962)
  • D.A. Kernahan

    On cleft lip and palate classification

    Plast Reconstr Surg

    (1973)
  • Kriens O. Lahshal. A concise documentation system for cleft lip, alveolus, and palate diagnoses. In: Kriens O, editor....
  • V. Spina

    A proposed modification for the classification of cleft lip and cleft palate

    Cleft Palate J

    (1973)
  • M.M. Tolarova et al.

    Classification and birth prevalence of orofacial clefts

    Am J Med Genet

    (1998)
  • Y.Q. Zhou et al.

    Diagnosis and classification of congenital craniofacial cleft deformities

    J Craniofac Surg

    (2006)
  • C. Delestan et al.

    New neonatal classification of unilateral cleft lip and palate-part 1: to predict primary lateral incisor agenesis and inherent tissue hypoplasia

    Cleft Palate Craniofac J

    (2013)
  • J.C. Doucet et al.

    New neonatal classification of unilateral cleft lip and palate part 2: to predict permanent lateral incisor agenesis and maxillary growth

    Cleft Palate Craniofac J

    (2013)
  • A.J. Luijsterburg et al.

    Classifying common oral clefts: a new approach after descriptive registration

    Cleft Palate Craniofac J

    (2013)
  • B.C. Wang et al.

    Use of two cleft lip and palate classification systems by nonsubspecialized health care providers

    Cleft Palate Craniofac J

    (2013)
  • D.M. Juriloff et al.

    Mouse genetic models of cleft lip with or without cleft palate

    Birth Defects Res A Clin Mol Teratol

    (2008)
  • J.C. Murray

    Gene/environment causes of cleft lip and/or palate

    Clin Genet

    (2002)
  • T. Sadler

    Langman's medical embryology

    (2012)
  • K. Sulik

    Orofacial embryogenesis: a framework for understanding clefting sites

  • D. Grosen et al.

    A cohort study of recurrence patterns among more than 54,000 relatives of oral cleft cases in Denmark: support for the multifactorial threshold model of inheritance

    J Med Genet

    (2010)
  • S. Kondo et al.

    Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes

    Nat Genet

    (2002)
  • M.J. van den Boogaard et al.

    MSX1 mutation is associated with orofacial clefting and tooth agenesis in humans

    Nat Genet

    (2000)
  • J.D. Noll

    The origin of the term “harelip”

    Cleft Palate J

    (1983)
  • R.C. Hennekam

    Gorlin's syndromes of the head and neck

    (2010)
  • C.P. Chen

    Prenatal sonographic diagnosis of median facial cleft should alert holoprosencephaly with premaxillary agenesis and prompt genetic investigations

    Ultrasound Obstet Gynecol

    (2002)
  • M.M. Cohen et al.

    Perspectives on holoprosencephaly: part II. Central nervous system, craniofacial anatomy, syndrome commentary, diagnostic approach, and experimental studies

    J Craniofac Genet Dev Biol

    (1992)
  • S. Yamada et al.

    Phenotypic variability in human embryonic holoprosencephaly in the Kyoto Collection

    Birth Defects Res A Clin Mol Teratol

    (2004)
  • B.D. Solomon et al.

    Genotypic and phenotypic analysis of 396 individuals with mutations in Sonic Hedgehog

    J Med Genet

    (2012)
  • E.E. Castilla et al.

    Congenital healed cleft lip

    Am J Med Genet

    (1995)
  • D. McDonald-McGinn et al.

    22q11.2 Deletion syndrome

  • R.J. Shprintzen et al.

    Morphologic significance of bifid uvula

    Pediatrics

    (1985)
  • E.W. Harville et al.

    Cleft lip and palate versus cleft lip only: are they distinct defects?

    Am J Epidemiol

    (2005)
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    Disclosures: The authors report no conflicts of interest.

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