Stephanie E. Watkins, PhD, MSPH, MSPTa∗, Robert E. Meyer, PhD, MPHb, Ronald P. Strauss, DMD, PhDc and Arthur S. Aylsworth, MDd,     aCenter for Health Promotion and Disease Prevention, University of North Carolina at Chapel Hill, 1700 Martin Luther King Jr Boulevard, Chapel Hill, NC, USA; bBirth Defects Monitoring Program, Division of Public Health, North Carolina Department of Health and Human Services, State Center for Health Statistics, 222 North Dawson Street, Cotton Building, Raleigh, NC 27603, USA; cUNC Center for AIDS Research, UNC School of Dentistry, UNC School of Medicine, University of North Carolina at Chapel Hill, 104 South Building, CB# 3000, Chapel Hill, NC 27599-3000, USA; dDepartments of Pediatrics and Genetics, University of North Carolina at Chapel Hill, CB# 7487, UNC Campus, Chapel Hill, NC 27599-7487, USA

∗Corresponding author. Email: wat@email.unc.edu

Orofacial clefts (OFCs) include a broad range of facial conditions that differ in cause and disease burden. In the published literature, there is substantial ambiguity in both terminology and classification of OFCs. This article discusses the terminology and classification of OFCs and the epidemiology of OFCs. Demographic, environmental, and genetic risk factors for OFCs are described, including suggestions for family counseling. This article enables clinicians to counsel families regarding the occurrence and recurrence of OFCs. Although much of the information is detailed, it is intended to be accessible to all health professionals for use in their clinical practices.

Keywords

Epidemiology

Orofacial clefts

Classification

Genetics

Key points

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 resulting from an intrinsically abnormal developmental process.”1 On the other hand, a disruption is a “morphologic defect of an organ, part of an organ, or a larger region of the body resulting from the extrinsic breakdown of or an interference with, an originally normal developmental process.”1 In contrast to a malformation, the developmental potential of the involved organ was originally normal and “an extrinsic factor such as an infection, teratogen, or trauma interfered with the development, which thereafter proceeded abnormally.”1 An example of an OFC caused by a disruption would be one caused by a swallowed amniotic band.

The term deformation (or deformity) should be reserved for “an abnormal form, shape, or position of a part of the body caused by mechanical forces,” such as plagiocephaly.1 Although nasal collapse and skeletal asymmetry may be secondary deformities in a child with a repaired cleft lip, the cleft itself is a malformation not a deformity. Finally, the term dysplasia describes “an abnormal organization of cells into tissues and its morphologic results.”1 Hence, we have a group of conditions called ectodermal dysplasias, which involve derivatives of the embryonic ectoderm and may have associated OFCs, and skeletal dysplasias, some of which also have OFCs associated with them.

Most OFCs are considered malformations, unless there is clear evidence that it might be a disruption. Even when a cleft is associated with an underlying bone dysplasia or genetic syndrome it is considered a malformation because the process of embryologic tissue growth and fusion was abnormal (because of the underlying syndrome).

The use of the terms isolated and syndromic is another area of potential confusion when describing OFCs. Isolated cleft palate may refer to cleft palate without cleft lip or it may be used to describe a patient who does not have any other malformations or anomalies. In addition, nonfamilial clefts are sometimes called isolated.

The word syndrome means “a pattern of multiple anomalies thought to be pathogenetically related.”1 A malformation is syndromic if patients have more than one malformation involving more than one developmental field or region of the body. In clinical practice, this usually means birth defects in more than one organ system. For syndromes, pathogenesis is usually unknown, whereas underlying causal factors may be known or unknown.

Some researchers will use the term syndromic in a more restrictive fashion to refer only to patients with syndromes of known or suspected cause (eg, chromosomal syndromes, Mendelian syndromes, eponymic syndromes). The authors suggest calling these syndromes of known cause in order to differentiate them from idiopathic syndromic cases or syndromic cases of unknown cause, which will include OFCs of unknown cause with other major anomalies. A major anomaly is commonly defined as a structural or functional variation from the norm that is of medical, surgical, or cosmetic significance. Both cleft lip with or without cleft palate and posterior cleft palate without cleft lip may occur in association with other major birth defects. Posterior cleft palate without cleft lip is more commonly syndromic than cleft lip with or without cleft palate (Table 1).2–10

Finally, the difference between sporadic and simplex events should be highlighted. Sporadic refers to a chance event, whereas simplex refers to a single occurrence of a condition in a family.11 Simplex, or nonfamilial, cases can result from a variety of genetic and nongenetic causes, whereas truly sporadic cases are pure accidents of development. In most cases of simplex OFCs, we simply do not know the cause and, therefore, it is not appropriate to speculate that these are sporadic. As Pagon pointed out, we “need to be very clear when we use the term ‘sporadic’ that it is a chance event with little risk of recurrence and that when we use the term ‘simplex,’ risk of occurrence in relatives remains a possibility.”11

Throughout this review, the authors use the terms 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) in order to avoid ambiguity.

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...