Cleft Palate and Lip

Cleft lip and cleft palate are among the most common congenital anomalies of the face, arising when the facial prominences and palatal shelves that build the lip and roof of the mouth fail to fuse during the embryonic and early fetal periods. They may occur alone or together, in isolation or as part of a recognised syndrome.

Definition

Cleft lip is a failure of fusion of the medial nasal and maxillary prominences forming the upper lip, while cleft palate is a failure of fusion of the palatal shelves forming the roof of the mouth; the two can occur separately or together and may be isolated (nonsyndromic) or part of a malformation syndrome.

Scope

This entry covers the embryology of lip and palate formation, the developmental events whose failure produces clefting, and the genetic and environmental influences that contribute to it. It treats orofacial clefting as a developmental and epidemiological topic for reference and education, and does not provide diagnostic, surgical, or treatment guidance.

Core questions

• How do the facial prominences and palatal shelves normally fuse to form the lip and palate?
• Why are cleft lip with or without cleft palate and isolated cleft palate considered developmentally and aetiologically distinct?
• What genetic and environmental factors contribute to orofacial clefting?
• How does the timing of fusion explain the range of cleft phenotypes?

Key concepts

• Facial prominences and their fusion
• Primary and secondary palate
• Palatal shelf elevation and fusion
• Cleft lip with or without cleft palate (CL/P)
• Isolated cleft palate (CP)
• Syndromic versus nonsyndromic clefting
• Multifactorial gene-environment causation

Key theories

Fusion-failure model and the CL/P versus CP distinction

The upper lip forms by fusion of the medial nasal and maxillary prominences in the embryonic period, while the secondary palate forms later by elevation and fusion of the palatal shelves; because these are separate developmental events, cleft lip with or without cleft palate and isolated cleft palate are treated as distinct entities with partly different genetic and environmental causes.

Mechanisms

The upper lip is completed in the embryonic period when the medial nasal prominences merge with each other and with the maxillary prominences; failure of this merging leaves a cleft of the lip, which may be unilateral or bilateral. The secondary palate forms later as the bilateral palatal shelves grow downward beside the tongue, then elevate above it and fuse with one another and with the primary palate and nasal septum; if the shelves fail to elevate, meet, or fuse, a cleft of the palate results. Because lip and palate formation are temporally and developmentally separable, cleft lip with or without cleft palate tends to share causes distinct from those of isolated cleft palate. Most clefting is multifactorial, with susceptibility genes interacting with environmental exposures, while a substantial minority occurs within defined syndromes.

Clinical relevance

The developmental timing and anatomy of clefting explain the spectrum of presentations and why lip and palate clefts can occur independently. This entry describes those developmental origins and the epidemiology of orofacial clefts for educational reference; it is not a source of diagnostic criteria, surgical timing, or feeding and treatment recommendations.

Epidemiology

Orofacial clefts are among the most common craniofacial birth defects, with birth prevalence varying by ancestry, geography, and sex, and differing between cleft lip with or without cleft palate and isolated cleft palate. A range of genetic loci and environmental factors have been associated with risk, and the relative contributions continue to be refined through genetic epidemiology.

Evidence & guidelines

The evidence base combines population-based epidemiology with genetic and developmental studies. The Lancet review by Mossey and colleagues synthesised the clinical and epidemiological picture, and the Nature Reviews Genetics review by Dixon and colleagues integrated genetic and environmental understanding; standard embryology texts supply the developmental framework. Surgical and multidisciplinary management is addressed by clinical sources outside the scope of this educational entry.

History

Orofacial clefting has long been studied both as a surgical condition and as a model of multifactorial inheritance. The recognition that cleft lip with or without cleft palate and isolated cleft palate are aetiologically distinct shaped twentieth-century genetic epidemiology, and the advent of genome-wide approaches in the early twenty-first century, synthesised in reviews such as Dixon and colleagues, refined the catalogue of susceptibility genes and gene-environment interactions.

Debates

How much of nonsyndromic clefting is explained by identified genetic variants?

Genome-wide studies have identified multiple susceptibility loci, but individually they account for only part of the heritability of nonsyndromic orofacial clefts, leaving open questions about missing heritability and the role of gene-environment interaction.

Key figures

• Peter A. Mossey
• Michael J. Dixon
• Jeffrey C. Murray
• William C. Shaw

Seminal works

• mossey-2009
• dixon-2011

Frequently asked questions

Why can cleft lip occur with or without cleft palate?

The lip and the secondary palate form by separate fusion events at different times, so a disturbance affecting lip fusion may or may not also affect later palatal fusion; this is why cleft lip with or without cleft palate is grouped separately from isolated cleft palate.

Is orofacial clefting inherited?

Most cases are multifactorial, resulting from a combination of susceptibility genes and environmental factors; a substantial minority occur as part of recognised malformation syndromes with defined genetic causes.