Physical Examination
Cleft lip with or without cleft palate
Cleft lip (CL) can occur either unilaterally (on the left or right) or bilaterally. The line of cleft always starts on the lateral part of the upper lip and continues through the philtrum to the alveolus between the lateral incisor and the canine tooth, following the line of the sutura incisiva up to the foramen incisivum. The clefting anterior to the incisive foramen (ie, lip and alveolus) is also defined as a cleft primary palate.
CL may occur with a wide range of severity, from a notch located on the left or right side of the lip to the most severe form, bilateral CL and alveolus that separates the philtrum of the upper lip and premaxilla from the rest of the maxillary arch (see the image below).
The mildest form is a microform and is a subtler expression of the cleft lip with or without cleft palate (CL/P) phenotype; it can typically involve small defects such as a notch located on the lip, also called forme fruste [40] or congenital healed CL, [41] and alveolar arch or asymmetrical drooping of the nostril. [42] Most often, these CL microforms occur unilaterally. Microform of CL is a rarely reported birth defect that occurs in 6 cases per 1,000,000 live births. [41]
The phrase “possible carriers” was used to search in families afflicted with orofacial clefts. [42] The investigation was carried out in 153 families of probands with nonsyndromic CL/P. In possible carriers (individuals in between two affected individuals; for example, a child and mother's mother are affected with a cleft, so the mother is a possible carrier), there was nearly always some microform with a higher incidence in all relatives of the subject; the asymmetrical drooping of the nose was the most frequent microform. The microforms may be used as a prognostic criterion.
Family prognosis is generally worse if any microform has been found in near relatives of the patient. In a family without CL/P, the incidence of a microform may increase the risk for clefting, but the actual probability is low. However, in a case of consanguineous marriage, the cleft microforms found in both partners should serve as a warning signal. The incidence of microforms in a certain population group (or in a certain area) must be taken into account in studies concerning the epidemiology in order to prevent erroneous interpretation of the findings. [42]
An important contribution to the classification of CL has been identifying and defining CL subphenotypes.
Marazita presented evidence that subepithelial (occult) defects of the superior orbicularis oris (OO) muscle represent the mildest form of the lip portion of CL/P. [43] This review provided descriptive histology of OO muscles from cadavers, assessed the rate of OO defects in unaffected relatives of individuals with CL/P via ultrasonography (US), and compared with controls and sequence BMP4 in non-CL/P individuals with OO defects. Non-CL/P relatives of individuals with overt CL/P had a significantly higher frequency of OO defects than controls with no family history of CL/P.
A pattern of disorganized OO muscle fibers was noted in those individuals with OO discontinuities diagnosed via US. [43] Sequencing of BMP4 found a significant increase in potentially damaging mutations in individuals with OO defects versus controls. This is significant support for the hypothesis that subepithelial OO muscle defects are a mild manifestation of the lip portion of the CL/P phenotype.
Suzuki et al also used US to detect subtle defects of the OO muscle (subepithelial defects). [44] Histologic studies showed disorganization of muscle fibers and excess connective tissue in comparison with normal OO muscles. The BMP4 mutation frequency for overt CL/P cases alone was not significantly greater than for controls, but the frequency for microform plus OO muscle cases was significantly greater than for controls. Furthermore, BMP4 mutation frequency was significantly lower in overt CL/P cases than in microform plus OO muscle cases.
These results suggested that amino acid alteration in BMP4 resulted in delayed lip closure (resulting in the appearance of a healed scar) or that actual healing of the cleft occurred by an unknown mechanism. BMP4 has a role in microform and subepithelial clefting that is consistent with the speculation that a genetic pathway may be involved in both wound healing and CL/P.
Another study employed US to compare the frequency of discontinuities in the OO muscle in 525 unaffected relatives of individuals with non-CL/P vs 257 unaffected controls. [45] OO muscle discontinuities were observed in 10% of the non-CL/P relatives, compared with 5.8% of the controls—a statistically significant increase. Male relatives had a higher rate of discontinuities than male controls did (12% vs 3.2%). Female relatives also had a higher rate of discontinuities than female controls did, but the increase was not statistically significant (8.9% vs 7.4%).
These data confirm the hypothesis that subepithelial OO muscle defects are a mild manifestation of the CL phenotype. Identification of subepithelial OO muscle defects may be important in a clinical setting as a means of providing more accurate recurrence risk estimates to relatives in cleft families. Furthermore, the expansion of the non-CL/P phenotypic spectrum should improve the power of genetic studies.
When CL continues from the foramen incisivum further through the sutura palatina in the middle of the palate, a cleft lip and palate (CLP), either unilateral or bilateral, is present (see the image below). A wide range of severity may be observed. The cleft line may be interrupted by soft (skin or mucosa) bridges, hard (bone) bridges, or both, corresponding to a diagnosis of an incomplete cleft. This occurs in unilateral and bilateral CLP.
Cleft palate
Cleft palate (CP; see the images below) is etiologically and embryologically different from CL/P.
Several subtypes of CP can be diagnosed on the basis of severity. The uvula is the place where the minimal form of clefting of the palate is observed. (However, a relatively high prevalence of this anomaly in the general population suggests that a certain proportion may represent the very far end of a normal variability.) A more severe form is a cleft of the soft palate. A complete CP constitutes a cleft of the hard palate, soft palate, and cleft uvula. The clefting posterior to the incisive foramen is defined as a cleft of secondary palate (see the image below).
In a significant proportion of patients, the cleft of the hard palate is covered by mucosa and continues through the soft palate, forming a so-called submucous CP. A submucous CP may occur in the hard palate only and continue to the open cleft of the soft palate, or it may occur as a submucous cleft of the soft palate with or without a notch into the hard palate. Careful clinical examination may reveal a blue triangle in continuation of the cleft of the soft palate, which represents a cleft of the bone palate underneath mucosa (see the image below).
The palate cleft may take two distinguishable forms: a V shape, which is most common in isolated clefts, or a U shape, which is most common in Robin sequence (see Pierre Robin Malformation) and in syndromic clefts.
The CP posterior to the incisive foramen is defined as the cleft of the secondary palate. CL and cleft of the palate anterior to the incisive foramen (unilateral or bilateral) is defined as the cleft of primary palate (thus, in bilateral CL, premaxilla is separated from lateral palatal segments). The bifid uvula is a sign that adenoidectomy may result in hypernasal speech if a complete adenoidectomy is done.
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Classification of orofacial clefts.
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Examples of cleft lip.
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Examples of cleft lip and palate.
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Examples of cleft palate.
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Submucous cleft palate.
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Bilateral cleft lip on ultrasound.
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Median cleft lip on ultrasound.
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Prevalence of orofacial clefts (Tolarova and Cervenka, 1998).
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Recurrence risk in cleft lip with or without cleft palate.
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Highest and lowest risk of recurrence of cleft lip with or without cleft palate.
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Recurrence risk in cleft palate.
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Etiology of cleft lip and palate anomalies.
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Multifactorial threshold model for the distribution of liability for cleft lip and palate.
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Four-threshold multifactorial threshold model of the liability for cleft lip and palate.
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Recurrence of clefts in supplemented and nonsupplemented groups.
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Prevention of cleft lip and palate by periconceptional vitamin (with particularly high folic acid) supplementation.
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Recurrence of clefts in supplemented and nonsupplemented groups, severity of cleft.
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Decreased occurrence of orofacial clefts.
