Patients who have cleft lip or palate face significant lifelong communicative and aesthetic challenges and difficulties with deglutition. Management of patients who have orofacial clefting requires an understanding of the anatomy and pathophysiology associated with clefting and the developmental difficulties encountered by these patients. This article describes current surgical concepts and principles of cleft care. Advances in the embryology and genetics of orofacial clefting are also discussed. It is expected that the care of patients who have clefts will continue to evolve because of advances in the fields of tissue engineering, genetics, and fetal surgery.
Orofacial clefts are the most common craniofacial birth defects, second only to clubfoot in frequency of major birth anomalies . Patients who have cleft lip or palate face significant lifelong communicative and aesthetic challenges, and difficulties with deglutition. The complex medical, ancillary, and psychosocial interactions necessary in the management of these patients warrants a multidisciplinary team approach . Care of the cleft patient can be both challenging and rewarding.
Epidemiology
The overall incidence of orofacial clefting is typically quoted as 1 in 700 live births . Cleft lip, with or without cleft palate (CL[P]), is an epidemiologically and etiologically distinct entity from isolated cleft palate (CP) . Cleft lip is associated with cleft palate in 68% to 86% of cases . The incidence of CL(P) varies significantly by racial group and with socioeconomic status, with an incidence of 1 in 1,000 births in whites, 1 in 500 births in Asians and Native Americans, and approximately 1 in 2,400 to 2,500 births in people of African descent . The incidence of CP does not have the same ethnic heterogeneity and is typically quoted as 1 in 1,500 to 2,000 live births . Between 60% and 80% of CL(P) patients are male, but a predominance of female infants affected by isolated cleft palate has been recognized . Unilateral CL(P) is twice as common as bilateral CL(P), and usually affects the left side .
Causative factors
Although most children who have orofacial clefts are otherwise normal, the proportion of affected individuals who have recognized patterns of malformation has increased steadily over the years as cleft teams have incorporated the services of geneticists and dysmorphologists ( Tables 1 and 2 ). More than 300 syndromes are known to be associated with orofacial clefting, but CP is more likely to be syndromic than CL(P). Approximately 14% to 30% of CL(P) cases are associated with multiple anomalies compared with 42% to 54% of CP cases .
| Genetic disorders | Recognized patterns with unknown genesis | Teratogens a |
|---|---|---|
| Down syndrome | Amniotic band sequence | Anticonvulsant phenotype |
| Smith-Lemli-Opitz syndrome | Aicardi syndrome | Fetal alcohol syndrome |
| Aarskog syndrome | Kabuki make-up syndrome | Maternal diabetes |
| Coffin-Siris syndrome | Craniofrontonasal dysplasia | Maternal smoking |
| van der Woude syndrome | Hypertelorism microtia clefting syndrome | Maternal folate deficiency |
| Waardenburg syndrome | Focal dermal hypoplasia syndrome | — |
| Ectodermal dysplasia syndromes (Ectrodactyly-ectodermal dysplasia-clefting, Hay-Wells, and Rapp-Hodgkin syndromes) | — | — |
| Distal arthrogryposis type 2 | — | — |
| Fryns syndrome | — | — |
| Popliteal pterygium syndrome | — | — |
| 22q deletion syndromes (DiGeorge syndrome, Shprintzen syndrome, and CHARGE association) | — | — |
| Wolf-Hirschhorn syndrome | — | — |
| Basal cell nevus syndrome | — | — |
| Kallman syndrome | — | — |
| Nail patella syndrome | — | — |
| Genetic disorders | Recognized patterns with unknown genesis | Teratogens a |
|---|---|---|
| Down syndrome | Pierre-Robin sequence | Anticonvulsant phenotype |
| Prader-Willi syndrome | Goldenhar syndrome | Fetal alcohol syndrome |
| Camptomelic dysplasia | Kabuki make-up syndrome | Thalidomide |
| Stickler syndrome | Mobius sequence | Dioxin |
| Holoprosencephaly | Klippel-Feil syndrome | Maternal smoking |
| de Lange syndrome | Silver-Russell syndrome | — |
| Spondyloepiphyseal dysplasia congenita | Beckwith-Wiedemann syndrome | — |
| Treacher-Collins syndrome | — | — |
| Cleft palate–short stature syndrome | — | — |
| 22q deletion syndromes (DiGeorge syndrome, Shprintzen syndrome, and CHARGE association) | — | — |
| Diastrophic dysplasia | — | — |
| Orofaciodigital syndrome type I | — | — |
| Otopalatodigital syndrome type I | — | — |
| Limb mammary syndrome | — | — |
| Nager syndrome | — | — |
| Smith-Lemli-Opitz syndrome | — | — |
| X-linked cleft palate with ankyloglossia | — | — |
| Apert syndrome | — | — |
| Marfan syndrome | — | — |
| Turner syndrome | — | — |
| Cleidocranial dysostosis | — | — |
The cause of isolated orofacial clefting is believed to be multifactorial . Although clefting tends to cluster in families, its inheritance is not usually Mendelian and the discordance rate in monozygotic twins can be between 40% and 60% . Several growth and transcription factors, receptors, polarizing signals, vasoactive peptides, cell adhesion proteins, extracellular matrix components, and matrix metalloproteinases are involved in palatal development. These biomolecules are expressed in a tightly controlled complex cascade, disturbance of which can result in orofacial clefting . CL(P) has been associated with defects in the genetic loci for growth and transcription factors transforming growth factor-alpha (TGF-α), TGF-β2, TGF-β3, interferon regulatory factor-6 (van der Woude and popliteal pterygia syndromes), T-BOX 22 (X-linked cleft palate with ankyloglossia), P63 (ectodermal dysplasia syndromes), Msx1, and the goosecoid transcription factor; for the vasoactive peptide endothelin-1 (22q deletion syndromes); for the retinoic acid receptor-alpha and the fibroblast growth factor receptor-1 (Kallman syndrome); for the cell adhesion molecule nectin-1 (ectodermal dysplasia syndromes); and several other genes whose functions have not yet been elucidated . Similarly, CP has been associated with defects in the genetic loci for TGF-α, TGF-β3, T-BOX 22, and P63 (limb mammary syndrome); for the polarizing factor sonic hedgehog (holoprosencephaly); and the extracellular matrix proteins collagen type II and procollagen type XI (Stickler syndrome) . Single gene disorders are believed to cause only 15% of clefts. The phenotypic heterogeneity demonstrated in the single gene disorders and variable penetrance, even in monozygotic twins, suggest that environmental factors also contribute to orofacial clefting. The role of epigenetic influences, such as maternal smoking, maternal alcohol use, folate deficiency or disordered metabolism, steroid and statin use, and retinoid exposure, is currently being investigated (see Tables 1 and 2 ) .
Causative factors
Although most children who have orofacial clefts are otherwise normal, the proportion of affected individuals who have recognized patterns of malformation has increased steadily over the years as cleft teams have incorporated the services of geneticists and dysmorphologists ( Tables 1 and 2 ). More than 300 syndromes are known to be associated with orofacial clefting, but CP is more likely to be syndromic than CL(P). Approximately 14% to 30% of CL(P) cases are associated with multiple anomalies compared with 42% to 54% of CP cases .
| Genetic disorders | Recognized patterns with unknown genesis | Teratogens a |
|---|---|---|
| Down syndrome | Amniotic band sequence | Anticonvulsant phenotype |
| Smith-Lemli-Opitz syndrome | Aicardi syndrome | Fetal alcohol syndrome |
| Aarskog syndrome | Kabuki make-up syndrome | Maternal diabetes |
| Coffin-Siris syndrome | Craniofrontonasal dysplasia | Maternal smoking |
| van der Woude syndrome | Hypertelorism microtia clefting syndrome | Maternal folate deficiency |
| Waardenburg syndrome | Focal dermal hypoplasia syndrome | — |
| Ectodermal dysplasia syndromes (Ectrodactyly-ectodermal dysplasia-clefting, Hay-Wells, and Rapp-Hodgkin syndromes) | — | — |
| Distal arthrogryposis type 2 | — | — |
| Fryns syndrome | — | — |
| Popliteal pterygium syndrome | — | — |
| 22q deletion syndromes (DiGeorge syndrome, Shprintzen syndrome, and CHARGE association) | — | — |
| Wolf-Hirschhorn syndrome | — | — |
| Basal cell nevus syndrome | — | — |
| Kallman syndrome | — | — |
| Nail patella syndrome | — | — |
| Genetic disorders | Recognized patterns with unknown genesis | Teratogens a |
|---|---|---|
| Down syndrome | Pierre-Robin sequence | Anticonvulsant phenotype |
| Prader-Willi syndrome | Goldenhar syndrome | Fetal alcohol syndrome |
| Camptomelic dysplasia | Kabuki make-up syndrome | Thalidomide |
| Stickler syndrome | Mobius sequence | Dioxin |
| Holoprosencephaly | Klippel-Feil syndrome | Maternal smoking |
| de Lange syndrome | Silver-Russell syndrome | — |
| Spondyloepiphyseal dysplasia congenita | Beckwith-Wiedemann syndrome | — |
| Treacher-Collins syndrome | — | — |
| Cleft palate–short stature syndrome | — | — |
| 22q deletion syndromes (DiGeorge syndrome, Shprintzen syndrome, and CHARGE association) | — | — |
| Diastrophic dysplasia | — | — |
| Orofaciodigital syndrome type I | — | — |
| Otopalatodigital syndrome type I | — | — |
| Limb mammary syndrome | — | — |
| Nager syndrome | — | — |
| Smith-Lemli-Opitz syndrome | — | — |
| X-linked cleft palate with ankyloglossia | — | — |
| Apert syndrome | — | — |
| Marfan syndrome | — | — |
| Turner syndrome | — | — |
| Cleidocranial dysostosis | — | — |
The cause of isolated orofacial clefting is believed to be multifactorial . Although clefting tends to cluster in families, its inheritance is not usually Mendelian and the discordance rate in monozygotic twins can be between 40% and 60% . Several growth and transcription factors, receptors, polarizing signals, vasoactive peptides, cell adhesion proteins, extracellular matrix components, and matrix metalloproteinases are involved in palatal development. These biomolecules are expressed in a tightly controlled complex cascade, disturbance of which can result in orofacial clefting . CL(P) has been associated with defects in the genetic loci for growth and transcription factors transforming growth factor-alpha (TGF-α), TGF-β2, TGF-β3, interferon regulatory factor-6 (van der Woude and popliteal pterygia syndromes), T-BOX 22 (X-linked cleft palate with ankyloglossia), P63 (ectodermal dysplasia syndromes), Msx1, and the goosecoid transcription factor; for the vasoactive peptide endothelin-1 (22q deletion syndromes); for the retinoic acid receptor-alpha and the fibroblast growth factor receptor-1 (Kallman syndrome); for the cell adhesion molecule nectin-1 (ectodermal dysplasia syndromes); and several other genes whose functions have not yet been elucidated . Similarly, CP has been associated with defects in the genetic loci for TGF-α, TGF-β3, T-BOX 22, and P63 (limb mammary syndrome); for the polarizing factor sonic hedgehog (holoprosencephaly); and the extracellular matrix proteins collagen type II and procollagen type XI (Stickler syndrome) . Single gene disorders are believed to cause only 15% of clefts. The phenotypic heterogeneity demonstrated in the single gene disorders and variable penetrance, even in monozygotic twins, suggest that environmental factors also contribute to orofacial clefting. The role of epigenetic influences, such as maternal smoking, maternal alcohol use, folate deficiency or disordered metabolism, steroid and statin use, and retinoid exposure, is currently being investigated (see Tables 1 and 2 ) .
Embryology
Human facial development begins during the fourth week of intrauterine life when neural crest cells migrate and combine with the mesoderm to form the facial primordia . The philtrum and primary palate (that portion of the palate and alveolus anterior to the incisive foramen) begin to form at approximately 35 days’ gestational age by the coalition, growth, and differentiation of three embryonic prominences or processes ( Fig. 1 ). The central segment of the face, comprising the forehead, supraorbital ridges, nose, philtrum, and primary palate, is derived from the frontonasal process. The intermaxillary segment of the frontonasal process is itself formed by the fusion of the two medial nasal prominences. This intermaxillary segment gives rise to the philtrum and that portion of the maxilla that bears the incisor teeth . During the fifth and sixth weeks of intrauterine development, medial growth of the maxillary prominences, derived from the first branchial arches, results in fusion of the medial nasal and maxillary prominences to form the upper lip and anterior alveolus. Failure of fusion results in cleft lip and alveolus.
Formation of the secondary palate follows that of the primary palate. The secondary palate (that portion of the palate posterior to the incisive foramen) forms through the fusion of two paired outgrowths of the maxillary prominences, the palatal shelves ( Fig. 2 ). The palatal shelves appear during the sixth week of development as vertical projections into the oral cavity on either side of the tongue. During the seventh week, the shelves elevate, assume a horizontal orientation, and fuse, closing the secondary palate. This fusion begins at the incisive foramen, progresses toward the posterior palate, and is complete at about the 12th week of intrauterine life. Failure of fusion results in a cleft palate ( Fig. 3 ). The severity of the palatal cleft varies from submucous clefting to complete bilateral clefting extending to the maxillary alveolus . Although the tongue does not participate in palatal closure in the normal situation, altered tongue position may mechanically block fusion of the palatal shelves, as in the Robin sequence. The tongue musculature is known to become functional at about the time of palatal shelf elevation .
Preoperative assessment
Initial assessment and identification of associated anomalies
The initial assessment of the infant born with an orofacial cleft includes a birth history, thorough head and neck examination, and examination of the infant’s extremities to identify associated malformations (see Tables 1 and 2 ). A history of intrauterine growth retardation may indicate Smith-Lemli-Opitz or Wolf-Hirschhorn syndrome. Down-slanting lateral canthi may indicate Treacher-Collins or Aarskog syndrome, whereas up-slanting lateral canthi and epicanthal folds indicate Down or Smith-Lemli-Opitz syndrome. Down-slanting lateral canthi with hypertelorism, blepharoptosis, epicanthal folds and colobomata are physical signs present in Wolf-Hirschhorn syndrome. Hypertelorism, blepharoptosis, and a simian crease are also characteristic of Aarskog syndrome. Ankyloblepharon with entropion and absent eyelashes indicate Hay-Wells syndrome.
Auricular abnormalities can occur with any of the 22q deletion syndromes and Treacher-Collins syndrome. Unilateral microtia or anotia with hemifacial microsomia typifies Goldenhar syndrome. An enlarged, cauliflower, or calcified auricle, and associated laryngotracheomalacia suggest diastrophic dysplasia.
CL(P) or CP with lower lip pits is pathognomonic for van der Woude syndrome. A grimace should be elicited to assess facial nerve function to rule out Mobius sequence. Digital malformations or agenesis characterize Aarskog, Coffin-Siris, de Lange, Nager, Fryns, Smith-Lemli-Opitz, Silver-Russell, limb mammary, ectrodactyly-ectodermal dysplasia-clefting and otopalatodigital syndromes, and amnion rupture sequence . Patients who have orofaciodigital syndrome manifest hamartomas or lipomas of the tongue and digital malformations. Infants who have Robin sequence, otopalatodigital syndrome, Nager syndrome, Smith-Lemli-Opitz syndrome, Kabuki syndrome, Silver-Russell syndrome, and Stickler syndrome have characteristic micrognathia . As upper airway compromise complicates several of the syndromes associated with CP, these patients may require immediate stabilization by positioning, tongue-lip adhesion, mandibular distraction, or tracheotomy in severe cases before palatal repair. Certainly, children who have cleft with other malformations should be referred with their families to the cleft team geneticist or dysmorphologist .
Feeding
The most immediate concern in the care of the infant who has cleft, other than the airway, is nutrition. The extent of the cleft often correlates with the infant’s ability to feed. Patients who have clefts limited to the soft palate usually have normal sucking, whereas infants who have hard palate clefts are often unable to generate the negative pressure needed for normal sucking because of the oronasal communication. Impaired sucking can lead to weight loss and failure to thrive as the infant expends more energy in feeding than he or she is able to ingest.
Early swallowing therapy is required in the infant who has a complete CP to ensure near-normal feeding and growth. Parents can be taught to use squeeze bottles with cross-cut nipples to increase the flow of formula in concert with the infant’s suck. In general, most newborns who have clefts should be able to ingest 2 to 3 ounces of formula with assistance within 20 to 30 minutes. Frequent burping is required during feeding because of aerophagia. Alternatively, bottles with nipples specialized for CP feeding, such as the Haberman feeder, can be used to limit air ingestion. Frequent assessments by the cleft team speech and swallowing pathologist may be needed to establish parental confidence in feeding. Patients who fail to gain weight or demonstrate excessive aerophagia may require placement of a palatal obturator by the cleft team pedodontist. Patients who have CL(P) and associated protruding premaxillae, particularly those who have bilateral clefts, should undergo lip adhesion or premaxillary orthopedics at approximately age 12 weeks. Lip adhesion not only decreases the size of the palatal cleft by normalizing the position of the premaxilla, but also restores the sphincter function of the orbicularis oris, which improves feeding. Monthly assessments by the facial plastic surgeon are recommended to evaluate patient growth and development, and more frequent follow-up by the cleft team pediatrician may be needed in patients who have failure to thrive or developmental delay.
Otolaryngologic assessment
The abnormal insertion of the tensor veli palatini is believed to contribute to Eustachian tube dysfunction, middle ear disease, and the conductive hearing loss associated with CP. The placement of myringotomy tubes is routine at the time of CP repair . Because several multiple malformation syndromes associated with clefting (eg, Stickler syndrome, van der Woude syndrome, Klippel-Fiel syndrome, Waardenburg syndrome, Down syndrome, and diastrophic dysplasia) also manifest sensorineural hearing loss, hearing assessment by auditory brainstem response testing or other methods should be performed in the first months of life.
Psychosocial support
Families of infants who have clefts require counseling by a cleft team social worker or psychologist as they adjust to the stresses of caring for the infant and frequent interaction with medical professionals. This is particularly true of families whose infants were not diagnosed with a cleft while in utero, who have limited resources or support, or who have infants who have multiple anomalies. Stages of shock, denial, sadness, anger, and adaptation and reorganization have been described in parents of infants who have clefts .
Unilateral cleft lip
Anatomy
The cleft lip deformity results from deficiency and displacement of soft tissues, cartilage, and bone in the area of the cleft . The principle muscle of the lip is the orbicularis oris, which interdigitates with the other mimetic muscles of the midface and lower face ( Fig. 4 A) . In the cleft lip, there is discontinuity of the orbicularis oris in the region of the cleft, and the fibers of the orbicularis parallel the cleft margin, inserting on the alar base on the lateral side of the cleft, and on the columellar base and septum on the medial side of the cleft ( Fig. 4 B) . Moreover, the orbicularis oris is hypoplastic in the area of the cleft .
The abnormal muscular forces and maxillary osseous discontinuity result in an outward rotation of the premaxillary-bearing medial segment and retrodisplacement of the lateral segment ( Fig. 5 A). The muscular attachment to the caudal septum is also believed to result in its displacement out of the vomerine groove and into the noncleft nostril, which in turn results in shortening of the columella. The philtrum is short on the cleft side, the peak of Cupid’s bow is rotated superiorly, and the vermilion is also deficient in the region of the cleft. In the nasal tip, the domes are separated and the lateral crus is flattened on the cleft side .
The severity of cleft lip varies from clefts involving only the vermilion to full-thickness clefts involving all tissue layers. A malformation consisting of dehiscence of the orbicularis muscle with vermilion notching but intact overlying skin is termed a microform cleft . An incomplete cleft lip spares some of the superior portion of the upper lip. Anatomic dissections on stillborn infants reveal that the orbicularis oris muscle in the incomplete cleft lip does not cross the cleft unless the cutaneous bridge is at least one third of the height of the lip. Moreover, the orientation of the small amount of muscle that bridges the cleft in this situation is abnormal .
Timing of cleft lip repair
Generally, cleft lip repair with primary tip rhinoplasty is performed at age 3 months. The patient’s overall health status, including the presence of other congenital anomalies, may dictate that repair of the cleft be delayed, however. Widely followed preoperative guidelines include the rules of ten: weight at least 10 pounds, hemoglobin at least 10 g, white blood cell count less than 10,000/mm 3 , and age more than 10 weeks . Patients who have wide complete unilateral clefts or bilateral clefts with marked premaxillary protrusion may require staged repair with lip adhesion performed at age 3 months and definitive repair performed at age 5 to 6 months. When lip adhesion includes muscular repair across the cleft (eg, a Rose-Thompson straight-line repair), it has the advantage of increasing the length of the cutaneous portion of the lip, which facilitates the definitive repair. Alternatively, presurgical maxillary orthopedics may be used before lip repair in the case of the wide cleft, but is associated with increased cost and burden of treatment . Lip adhesion may also be used with a passive molding device to prevent collapse of the alveolar arch form .
Cheiloplasty techniques for the unilateral cleft lip
The first documentation of cleft lip repair occurred in the fourth century ad in China. This simple technique involved freshening and approximation of the cut cleft edges, and remained the standard of care until 1825 when von Graefe proposed the use of curved incisions to allow lengthening of the lip. His work provided the foundation for the Rose-Thompson technique and other straight-line closure repairs introduced in the early 1900s . The straight-line closures, however, had the disadvantage of vertical scar contracture leading to notching of the lip .
Several methods were developed to avert the scar contracture associated with the straight-line closures. These included numerous geometric repairs that were also designed to irregularize the lip scar . In the 1950s, Tennison and Randall introduced a triangular flap that created a Z-plasty in the lower portion of the lip scar. All of these techniques produced scars that violated the philtrum, however .
The Millard rotation-advancement technique, introduced in 1957, is the most widely used procedure for cleft lip repair because it places most of the scar along the natural philtral border and is more flexible than the geometric closures. Moreover, the Millard technique allows for complete muscular repair and primary cleft rhinoplasty, and minimizes the discarding of normal tissue. Its disadvantages include the need for extensive undermining and the risk for nostril stenosis on the cleft side ( Fig. 5 B) . The author’s modification of the technique is described below.
Surgical technique
Flap design
Commonly used reference points for flap design are illustrated in Fig. 6 and described as follows :
Point 1: Center or low point of Cupid’s bow
Point 2: Peak of Cupid’s bow on noncleft side
Point 3: Peak of Cupid’s bow, medial side of cleft
Point 4: Alar base, noncleft side
Point 5: Columellar base, noncleft side
Point 6: Commissure, noncleft side
Point 7: Commissure, cleft side
Point 8: Peak of Cupid’s bow, lateral side of cleft
Point 9: Superior extent of advancement flap
Point 10: Alar base, cleft side
Point x: Back-cut point
