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    Cleft Lip and Palate

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    Dec.03.2024

    Cleft Lip and Palate

    Synopsis

    Key Points

    • Cleft lip and palate are common congenital malformations characterized by variable degrees of deficient and displaced orofacial soft tissue, musculature, bone, and cartilage involving the soft palate, hard palate, lip, and nasal sill
      • Orofacial malformations present as 2 distinct entities: cleft lip with or without palatal clefting or cleft palate alone
    • Clefts of the lip can present as unilateral, bilateral, or, rarely, median malformations r1
      • Cleft lip with or without cleft palate is more common than cleft palate alone and is less likely to be associated with a congenital syndrome r1
    • Clefts of the palate can present with variable involvement of the posterior soft palate alone to a malformation involving the entire length of soft and hard palates
      • Occult submucous cleft may present without obvious malformation in palate with symptoms of velopharyngeal insufficiency (eg, feeding difficulty, speech impairment, eustachian tube dysfunction) later in life
      • Cleft palate alone is more commonly syndromic than cleft lip with or without cleft palate
    • Cleft lip with or without cleft palate and cleft palate alone may be associated with presence of other major congenital malformations
      • Additional significant congenital malformations involving other organ systems are present in up to 21% of patients overall with orofacial clefting
      • Numerous syndromes are associated with orofacial clefting; however, chromosomal anomalies are rare in patients with isolated orofacial clefting
    • Majority of orofacial clefting is diagnosed on physical examination in the neonate; overall, about 25% of cleft lips with or without cleft palate are diagnosed antenatally by routine prenatal ultrasonography
    • Challenges for patients with orofacial clefting may include distortion of basic anatomy, feeding problems, dental problems, speech disorders, eustachian tube dysfunction, and deficient maxillofacial growth r2
    • Management approach requires an interdisciplinary team with experience in the diagnosis and treatment of patients with cleft lip and/or palate
    • Immediate concerns for infants with cleft palate with or without cleft lip include attention to ability to maintain airway patency and ability to feed
    • Surgery is the primary treatment to establish normal facial anatomy and feeding function and to reduce hearing and speech impediments r3
    • Long-term interdisciplinary care is necessary to monitor for and manage potential complications r4
    • Prognosis is highly dependent on type and degree of orofacial cleft and affected by the presence of other associated congenital anomalies or syndromes
    • Surgery has an excellent rate of success as the primary treatment to achieve normal facial anatomy and feeding ability and to reduce hearing and speech impairment

    Urgent Action

    • Neonates and infants with cleft palate often have difficulty with feeding; early assessment of ability to feed effectively and initiation of specialized feeding strategies are often necessary in the immediate neonatal period
    • Neonates and infants with syndromic clefting associated with abnormalities in the mandible (eg, Pierre Robin sequence) may have difficulty maintaining patency of the upper airway; prone positioning or upper airway adjuncts may be required to maintain airway patency

    Pitfalls

    • Patients with cleft lip and palate are likely to require several surgeries to achieve normal anatomy and function r3
      • Coordinated interdisciplinary care and preoperative planning is important to minimize effect on dentition, hearing and language development, and cosmetic outcome as the patient matures
    • Early diagnosis of occult submucous cleft is important to maximize outcome; suspect diagnosis in infants and children with feeding difficulties, persistent eustachian tube dysfunction, and speech impairment
      • Implementation of ancillary resources (eg, special feeding strategies, speech and language therapy) and possible surgical correction of velopharyngeal insufficiency may improve outcomes

    Terminology

    Clinical Clarification

    • Cleft lip and palate are common congenital malformations characterized by variable degrees of deficient and displaced orofacial soft tissue, musculature, bone, and cartilage involving the soft palate, hard palate, lip, and nasal sill r3
      • Orofacial malformations present as 2 distinct entities: cleft lip with or without palatal clefting, or cleft palate alone r1
    • Cleft lip refers to a spectrum of variable abnormalities involving the primary palate (ie, tissue anterior to the incisive foramen or premaxillary area) including alveolar ridge, lip, facial area inferior to the nose, and nasal sill (ie, inferior aspect of naris) r5
    • Cleft palate refers to a spectrum of variable abnormalities involving the secondary palate (ie, tissue posterior to the incisive foramen, including soft palate, hard palate, and uvula) r3

    Classification

    • Classification based on clinical manifestations of malformation
      • Multiple classification schemes are available: r6
      • Cleft lip
        • Onizuka classification system r6r7
          • Complete cleft
            • Variable malformation of lip and alveolus extends to the nasal floor r1
          • Incomplete cleft
            • Variable malformation of lip and alveolus but does not extend to the nasal floor (ie, bridge of tissue separates cleft from nares) r1
            • Subdivided into quarters with respect to degree of lip involvement (eg, cleft up to one-quarter, one-half, three-quarters, or whole lip)
          • Microform cleft (forme fruste)r6
            • Least severe form of malformation that may manifest as:
              • Notch of vermilion-free margin or vermilion border
              • Striae of lip
              • Nasal deformity without lip deformity
      • Cleft palate
        • Veau classification system r3r6
          • Type I: cleft of the soft palate only
          • Type II: clefts of the hard and soft palate restricted to the secondary palate (palate posterior to the incisive foramen)
          • Type III: unilateral cleft involving secondary and primary palate (palate anterior to the incisive foramen)
          • Type IV: bilateral cleft with complete isolation of the median tubercle
        • Submucous cleft palate
          • Variant considered to be a microform of cleft palate alone r8
          • Associated with occult muscle malformations r3
          • Midline musculature of soft palate is abnormally directed despite absence of obvious palatal malformation r9
    • Classification based on presence or absence of additional significant malformation
      • Syndromic or nonisolated clefts
        • Characterized by more than 1 malformation involving more than 1 developmental field or region of the body r8
          • Subdivided into the following:
            • Syndrome of known or suspected cause r8
              • Associated with an identifiable single gene abnormality, chromosomal defect, or teratogen r10
            • Syndrome of unknown cause r8
              • Unknown or undetermined cause for other major associated anomalies r8
          • Cleft palate alone is more commonly syndromic than cleft lip with or without cleft palate r8
      • Nonsyndromic or isolated clefts r8r10
        • Absence of other significant associated anomalies (ie, other structural or functional variations from norm that are of medical, surgical, or cosmetic significance), andr10
        • Absence of known or identifiable single genetic, chromosomal, or known teratogenic cause of clefting r10

    Diagnosis

    Clinical Presentation

    History

    • Most common presentations
      • Most orofacial clefts are diagnosed at birth on examination r5
      • Overall, about 25% of cleft lips with or without cleft palate are diagnosed antenatally r5
        • Cleft palate alone is difficult to detect on routine prenatal ultrasonographic studies
        • Follow-up fetal MRI and 3-dimensional ultrasonography, when available, may better characterize fetal orofacial malformations r11r12
      • Prenatal testing may show congenital syndrome associated with clefting r13
        • Detection of additional anomalies on ultrasonogram is an important indicator of the possibility of an underlying chromosomal defect in fetus with known orofacial malformation r8
    • Submucous cleft r9c1
      • Often presents later in infancy and childhood with symptoms of velopharyngeal insufficiency c2
        • Feeding difficulty and swallowing problems (eg, choking, cyanosis with feeds, aerophagia, nasal reflux) r3c3c4c5c6c7c8
          • May result in failure to thrive r14
        • Abnormal speech with articulation errors and hypernasal voice r15c9c10
        • Hearing problems from defective eustachian tube function with associated otitis media with effusion r3c11c12
    • Familial inheritance
      • Occasionally positive for a parent or sibling with orofacial clefting c13

    Physical examination

    • Malformation in the palate, lip, or both, noted at birth c14c15
      • Cleft lip and cleft palate malformations most commonly occur together r13
        • Unilateral cleft lip and palate account for about one-half of all cleft abnormalities r6
          • Vast majority of bilateral cleft lip malformations are associated with palatal clefting r5
        • Cleft lip alone accounts for about 20% of all cleft abnormalities r5
      • Cleft palate alone accounts for about one-third of all cleft abnormalities r3
      • Phenotypes of orofacial clefting malformations are highly variable
    • Clefting of the primary palate r16r17r18
      • Malformation can be unilateral, bilateral, or central r10
        • Unilateral left-sided clefting is most common r5c16
        • Central clefting is rare and often associated with a congenital syndrome c17
      • Length of upper lip cleft is variable r6
        • May range from minimal lip malformation to a large, complete cleft extending through the lip and into the nose c18c19
        • Incomplete cleft is evidenced by a bridge of tissue separating cleft from nares
      • Depth of upper lip cleft is variable
        • May range from minimal clefting of the vermilion border to full-thickness malformation r13
      • Maxillary alveolar ridge variably involved
        • Often a malformation in alveolar ridge is associated with lip clefting c20
    • Clefting of the secondary palate
      • Length of midline cleft malformation is variable
        • Involvement ranges from the posterior soft palate alone to a malformation along the entire length of soft and hard palates c21c22c23
        • Submucous cleft may be occult without visible malformation in palate c24
    • Typical nasal deformities associated with cleft lip include: r2
      • Underprojection of the nose with poorly formed nasal tip c25c26
      • Wide horizontal nostrils and a flat alar dome owing to a lack of supporting bone structure and weak cartilage c27c28
      • Lack of nasal floor on the cleft side c29
      • Caudal septum and columella are deviated to the noncleft side in unilateral clefts c30
    • Submucous cleft palate examination findings may include: r5
      • Bony notch palpable at the posterior margin of the hard palate c31
      • Bifid uvula c32
      • Lucency or blue discoloration of the midline of the palate due to muscle diastasis (zona pellucida or translucent zone) c33
    • Dysmorphic features observed on physical examination that suggest an associated syndrome include: r13
      • Lower lip pits
        • Highly suggestive of van der Woude syndrome or popliteal pterygium syndrome c34c35c36
      • Auricular abnormalities c37
        • May be associated with 22q deletion spectrum and Treacher Collins syndrome c38c39
      • Micrognathia c40
        • May be associated with a number of congenital syndromes including Pierre Robin sequence or otopalatodigital, Nager, Smith-Lemli-Opitz, Kabuki, Silver-Russell, and Stickler syndromes c41c42c43c44c45c46c47
      • Down-slanting lateral canthi c48
        • May be associated with Treacher Collins, Wolf-Hirschhorn, or Aarskog syndromes c49c50c51
      • Up-slanting lateral canthi and epicanthal folds c52c53
        • May be associated with Down or Smith-Lemli-Opitz syndromes d1
      • Hypertelorism and blepharoptosis c54c55
        • May be associated with Wolf-Hirschhorn or Aarskog syndromes
      • Unilateral microtia or anotia with hemifacial microsomia c56c57c58c59
        • May be associated with Goldenhar syndrome c60
      • Absence of grimace with facial nerve palsy c61c62
        • May be associated with Möbius sequence
      • Hamartomas or lipomas of the tongue c63c64
        • May be associated with orofaciodigital syndrome c65
      • Digital malformations or agenesis
        • May be associated with amnion rupture sequence and a number of congenital syndromes including Aarskog, Coffin-Siris, de Lange, Nager, Fryns, Smith-Lemli-Opitz, Silver-Russell, ectrodactyly-ectodermal dysplasia-clefting, and otopalatodigital syndromes c66c67c68c69c70c71c72c73c74c75

    Associated congenital anomalies

    • Additional significant congenital anomalies are present in up to 21% of patients overall r19r20
      • Occurrence of associated anomalies is dependent on anatomical type of clefting
        • Incidence is about 28% in patients with both cleft lip and cleft palate r19
          • Patients with bilateral clefting and midline clefting have higher risk of associated anomalies than those with unilateral disease r21
        • Incidence is about 22% in patients with cleft palate alone r19
        • Incidence is about 8% in patients with cleft lip alone r19
      • Multiple associated malformations c76
        • Occur in at least 15% of patients overall r19
        • More likely associated with chromosomal anomalies or mental retardation r19
      • Types of associated anomalies (variably reported in literature)
        • Most commonly affected systems include the following:
          • Limb and the vertebral column anomalies c77c78
            • Account for about 33% of concomitant anomalies r19
            • May include club foot, polydactyly, syndactyly, clinodactyly, aplastic radius, and hemivertebrae c79c80c81c82c83c84
          • Cardiovascular anomalies c85
            • Account for about 25% of concomitant anomalies r22
            • May include atrial septal defect, ventricular septal defect, patent ductus arteriosus, tetralogy of Fallot, mitral valve prolapse, dextrocardia, and ventricular hypertrophy c86c87c88c89c90c91c92d2
          • Urogenital system anomalies c93
            • Account for about 25% of concomitant anomalies r23
            • May include cryptorchidism and dysplastic or polycystic kidney c94c95c96
          • Additional facial region anomalies
            • Account for about 21% of concomitant anomalies r23
            • May include dysmorphic facial features, skull malformation, macrocephaly, microcephaly, or bifid nose r23c97c98c99c100c101
        • Less commonly affected systems include:
          • Ocular
          • Central nervous system
            • May include learning disorders, developmental delay, epilepsy, holoprosencephaly, spina bifida, and cerebral atrophy r23c107c108c109c110c111c112
          • Gastrointestinal

    Causes and Risk Factors

    Causes

    • The cause of both cleft lip and/or palate is largely multifactorial with both genetic and environmental contributors r3c117
      • Development of orofacial clefting is a genetically complex event that results from the growth and fusion of abnormal embryonic tissue
      • Any interruption in the complex and tightly controlled cascade of events that contribute to normal orofacial development can lead to clefting r20
    • Cleft lip and palate result from failure of migration and fusion of the frontonasal, maxillary, medial, and lateral nasal prominences of the lower face between gestational weeks 6 and 12 r3c118c119
      • Underlying cause for cleft palate without cleft lip is thought to be pathogenetically distinct from that of cleft lip with or without cleft palate in terms of environmental influences and perhaps underlying genetic contributors
        • Primary palate and lip development
          • Occur between gestational weeks 4 and 6 r1
          • Normal closure of the medial frontonasal process with maxillary process occurs by the end of gestational week 6 r8
        • Secondary palate development
          • Fusion of palatal shelves of the maxillary process proceeds from an anterior to posterior direction during gestational weeks 8 through 12 r1
          • Normal closure of palatal shelves occurs by gestational week 12 r1
        • Genetic influences are poorly understood
          • Interactions between at least 3 and 14 gene loci may be involved in the development of nonsyndromic orofacial cleft malformations r24
          • Nonsyndromic cleft lip and palate is associated with known abnormalities in multiple chromosomes (eg, 1, 2, 4, 6, 11, 14, 17, 19) r3c120c121c122c123c124c125c126c127
          • Orofacial clefting is associated with known mutations in many regulatory genes (eg, transforming growth factors -α, -β2, -β3; interferon regulatory factor-6, T-box 22, P63, MSX1, goosecoid transcription factor) r13c128c129c130c131c132c133c134c135c136

    Risk factors and/or associations

    Age
    • Overall, about 1 in 690 neonates in the United States is born with an orofacial cleft r10c137
    • About 1 in 940 neonates in the United States is born with cleft lip, with or without cleft palate r10c138
    • About 1 in 1574 neonates in the United States is born with cleft palate alone r10c139
    Sex
    • Cleft lip with or without cleft palate is more common in males
      • 60% to 80% of patients are male r13
    • Cleft palate alone occurs with slightly increased frequency in females r5c140c141
    Genetics
    • Inheritance is complex and may be chromosomal, complex mendelian, or sporadic r5
    • Syndromic orofacial clefts (associated with another anomaly) generally follow Mendelian inheritance r25
      • Overall, about one-third of cleft malformations are associated with a congenital syndrome r20
      • Cleft palate alone is more likely to be associated with a malformation syndrome (up to 50%) than cleft lip with or without palatal clefting (about 15%) r3r13
      • More than 300 syndromes are associated with orofacial clefting; those most commonly associated include: r13
        • Velocardiofacial syndrome (22q11-deletion syndrome) (OMIM #192430) r26c142
          • Most common syndrome associated with cleft palate alone r3
          • Many phenotypic features can be present; most commonly dysmorphic facies (eg, vertical maxillary excess, malar flattening, relative mandibular retrusion, narrow palpebral fissure, small ears) and cardiac anomalies (eg, ventricular septal defect, tetralogy of Fallot)
          • Caused by microdeletion in 22q11.2 region; inheritance is autosomal dominant r26
        • Pierre Robin sequence (OMIM #261800) r27c143
          • About 15% of patients with cleft palate have Pierre Robin sequence r28
            • Palatal malformation usually assumes a characteristic U-shape r8
          • Condition is characterized by a group of anomalies including micrognathia or retrognathia, and glossoptosis, often accompanied by cleft palate alone
            • Anomalies may cause upper airway obstruction in the neonatal period
            • May occur as an isolated nonsyndromic malformation (about 40%) or as part of a syndromic malformation of known cause (eg, chromosomal, mendelian, teratogenic) r8
            • Most common genetic association is a sporadic mutation in SOX9 gene (region 17q24)
        • Van der Woude syndrome (OMIM #119300) r29c144
          • Most common syndrome associated with cleft lip and palate; up to 3% of patients with cleft lip and palate have van der Woude syndromer13
            • Cleft palate alone may also occur with this syndrome r8
          • Other dysmorphic features include lower lip pits, hypodontia, and ankyloglossia; may be associated with congenital heart malformations and Hirschsprung disease
          • Inheritance is an autosomal dominant mutation in IRF6 gene (region 1q32)
        • Others include: r13
          • Down syndrome (OMIM #190685) r30c145
          • Popliteal pterygium syndrome (OMIM #119500) r31c146
          • X-linked cleft palate with or without ankyloglossia (OMIM #303400) r32c147
          • Ectodermal dysplasia syndromes (OMIM #225060,129900) r33r34c148
          • Treacher Collins syndrome (OMIM #154500, 613717, 248390) r35r36r37c149
          • Stickler syndrome (OMIM #609508,108300) r38r39c150
          • Goldenhar syndrome (OMIM #164210) r40c151
    • Nonsyndromic orofacial clefts do not adhere to Mendelian inheritance r25
      • Variants involving a number of genes have been implicated
      • Variants in genes associated with syndromic orofacial clefts are found in approximately 10% of patients with clinical diagnosis of nonsyndromic oral cleft r25
      • Chromosomal anomalies are rare in patients with isolated orofacial clefting (ie, those without additional associated congenital malformations) r21r41
      • Familial inheritance of nonsyndromic orofacial clefts c152
        • Clefts are usually the same type in familial cases, although severity of clefting is variable within families r8
        • Heritability of cleft palate
          • Risk for an affected child is about 7% when 1 parent is affected r3
          • Risk for an affected child is about 2% when 1 sibling is affected with unaffected parents r3
          • Risk for an affected child is about 17% when both a parent and a sibling are affected r3
        • Heritability of cleft lip with or without cleft palate
          • Risk for an affected child is about 4% when 1 parent is affected or a sibling is affected with unaffected parents r5
          • Risk for an affected child is about 17% when both a parent a and sibling are affected r5
          • Familial recurrence risk appears associated with cleft severity
            • Risk for siblings of proband with bilateral clefting is higher than for siblings of proband with unilateral clefting r8
    Ethnicity/race
    • Racial variability exists with occurrence of cleft lip with or without cleft palate
      • Highest among Asians and Native Americans (1 in 450 live births) r3c153c154
      • Lowest among Black populations (1 in 2000 live births) r3c155
      • Intermediate incidence occurs among other ethnic populations (eg, White, Hispanic) c156c157
    • Cleft palate alone occurs independent of race r3
    Other risk factors/associations
    • In general, data regarding specific risk factors for cleft lip with or without cleft palate and cleft palate alone are somewhat difficult to separate
      • Magnitude of effects of various risk factors for orofacial clefting are different for cleft lip with or without cleft palate and cleft palate alone r8
        • In general, environmental factors are thought to contribute relatively more to risk for nonsyndromic clefting of primary palate than secondary palate
    • Risk factors for orofacial clefting may include:
      • Family history of orofacial clefting c158
      • Advanced maternal or paternal age r3r42c159c160
      • Gestational exposure to potential teratogens
      • Prepregnancy maternal diabetes r3r13c172
      • Gestational exposure to rubella and hypoxia r3r13c173c174
      • Possible associations may include: r20
        • Gestational exposure to corticosteroids or statins c175c176
        • Poor maternal vitamin B6 status c177
        • Maternal zinc deficiency c178
        • Maternal folate deficiency r13c179

    Diagnostic Procedures

    Primary diagnostic tools

    • Prenatal diagnosis c180
      • Overall, about 25% of cleft lips with or without cleft palate are diagnosed antenatally by routine prenatal ultrasonography r5
        • Assessment of the upper lip is a standard component of routine second trimester antenatal ultrasonography
        • Cleft lip and palate also be detected at the time of routine first-trimester ultrasonography, however diagnosis is less reliable r44
        • If cleft lip is detected, careful imaging of the palate is required as most fetuses also have palatal involvement
        • Cleft palate without lip clefting is difficult to detect on routine prenatal ultrasonogram; can be visualized by a routine hard palate sweep technique r1r5r45
      • 3-dimensional ultrasonography allows better characterization of fetal orofacial malformations and assessment for additional associated anomalies, particularly when cleft palate is suspected r1r21
        • Fetal MRI, when available, is obtained to further characterize details of fetal orofacial malformations and additional associated anomalies r11r12
      • Invasive testing to assess for chromosomal abnormalities (eg, amniocentesis, chorionic villus sampling) is recommended on an individualized basis depending on type of clefting, presence of associated structural anomalies, and presence of other suspicious prenatal abnormalities (eg, intrauterine growth restriction) r21
      • Prenatal genetic testing
        • Prenatal testing may be used to screen for chromosomal abnormalities
        • For isolated cleft palate a single nucleotide polymorphism array is recommended. For cleft lip, alveolus, and palate, or cleft lip with or without cleft alveolus, obtain cleft gene panel or whole exome sequencing r46
        • As per the International Society for Prenatal Diagnosis, diagnostic genome‐wide sequencing may be performed for the following indications: r47
          • If a fetus is found to have a single major anomaly or has multiple organ system anomalies that are suggestive of a possible genetic etiology but no genetic diagnosis was found after standard genetic testing, such as chromosomal microarray analysis, or for which the multiple anomaly "pattern" strongly suggests a single gene disorder with no prior genetic testing r47
          • Maternal or paternal history of prior undiagnosed fetus or child with a major single or multiple anomalies: r47
            • With recurrence of similar anomalies in current pregnancy without a genetic diagnosis after karyotype or chromosomal microarray analysis for the current or previous undiagnosed pregnancy r47
            • When parents present for preconception counseling but no sample is available from the affected proband, or if fetal sample is not obtainable in an ongoing pregnancy, sequencing can be offered to biological parents to evaluate for shared carrier status for autosomal recessive mutations that could explain fetal phenotype r47
    • Postnatal diagnosis
      • Physical examination is often the only diagnostic tool necessary to confirm condition r3
        • Occult submucous cleft may require confirmation by nasoendoscopy in consultation with otolaryngologist r5
    • Targeted additional investigations to assess for associated congenital anomalies and/or congenital syndromes may be indicated based on individual presentation, in consultation with geneticist, developmental pediatrician, and treatment team
      • Many infants with prenatally determined nonsyndromic clefting are found to have additional malformations after birth
        • Up to about one-quarter of infants with detailed prenatal ultrasonography may have additional malformation identified in the neonatal period r48
        • Patients with more extensive clefting are at higher risk of associated malformations and may require additional testing, even with otherwise normal examination findings r1
      • Additional testing based on physical examination findings may include:
        • Genetic testing (eg, karyotyping, chromosomal analysis, genome-wide microassay testing) c181c182c183
        • Central nervous system imaging (ie, ultrasonography or MRI)
        • Cardiac evaluation (eg, ECG, echocardiography)
        • Formal ophthalmology examination c184
    • Additional evaluation is often required during period of initial diagnosis and during childhood and may include assessments for the following: r3
      • Feeding dysfunction and risk for aspiration r49
        • Neonates and infants with cleft palate with or without cleft lip require individualized evaluation for feeding ability owing to their inability to sufficiently create adequate suction r50
        • First step is subjective observational assessments of feeding and nonnutritive sucking by specialized feeding nurse or lactation consultant r50
        • Obtain objective videofluoroscopic swallowing study if concerns develop (eg, choking, stridor, cyanosis with feedings) during observational assessment r51
          • Fiberoptic endoscopic evaluation of swallow is an alternate assessment modality sometimes obtained in the process of evaluation
      • Conductive and sensorineural hearing
        • Conductive hearing loss
          • Eustachian tube dysfunction is almost universally present in infants with cleft palate, with or without cleft lip
          • Tympanometry and pneumatic otoscopy r52c185
            • Both tests evaluate for presence of middle ear effusion; provides an indirect assessment eustachian tube function
            • Presence of persistent middle ear fluid may lead to conductive hearing loss and requires further evaluation by otolaryngologist
        • Sensorineural (cochlear) hearing loss
          • Up to 28% of infants with cleft palate fail newborn hearing screen r53
          • Audiometric testing r52r54
            • Screening assessments may include:
              • Auditory brainstem response testing (preferred) r55
              • Otoacoustic emissions testing r55
            • Failed screening requires comprehensive audiologic evaluation
      • Velopharyngeal function for patients with cleft palate
        • Deficient velopharyngeal closure (ie, inability of soft palate to completely block nasopharynx) creates an inefficient seal during speech and leads to speech complications
        • Nasopharyngoscopy performed during articulation is the most common procedure and is typically performed in consultation with a speech pathologist r4c186
        • Multiplanar videofluoroscopy may be used to further characterize deficits noted on nasopharyngoscopy

    Imaging

    • Prenatal imaging modalities
      • Prenatal transabdominal ultrasonography c187
        • Sensitivity of routine gestational scan at 20 weeks is in general poor for detection of orofacial clefting r56
          • Visualization of the palate is particularly difficult owing to acoustic shadowing from facial bones and lack of lip and alar base involvement r1r5
        • Reported sensitivity is extremely variable, from 9% to 100%;r57r56specificity is high r57r5
        • Accuracy is highly variable and dependent on experience of sonographer, maternal body habitus, gestational age, fetal position, amount of amniotic fluid, and type of cleft r56
      • Prenatal 3-dimensional ultrasonography c188
        • Provides more precise characterization of orofacial malformations compared with routine prenatal ultrasonography r56
          • Imaging of the palate by any ultrasonographic modality is difficult and does not exclude presence of cleft palate r56
        • Improves precision for detection of associated malformations involving other organ systems compared with routine prenatal ultrasonography
      • Fetal MRI c189
        • Improved diagnostic accuracy of orofacial clefting compared with ultrasonographic imaging r56
        • Pooled sensitivity of 97% and specificity of 94% for diagnosing cleft palate in fetuses at risk for orofacial clefts according to a recent meta-analysis r58
        • Less dependent on optimal amniotic fluid volume, fetal position, and maternal body habitus compared with ultrasonography r56
        • Acoustic shadowing does not limit images obtained by fetal MRI r56
        • Shows presence of most associated intracranial and/or extracranial anomalies r1
        • Indications include instances in which:
          • Clefting of lip and/or palate is suspected but not well visualized on 3-dimensional ultrasonogram r1
          • Associated anomalies are suspected but not identified on 3-dimensional ultrasonogram r1
    • Postnatal imaging modalities
      • Videofluoroscopic swallowing study r59c190
        • Represents a modified barium-swallowing examination; study captures sequential images of contrast-impregnated food and liquid transported throughout the entire upper digestive tract (eg, oral cavity, pharyngeal cavity, esophagus)
        • Enables visualization of physiology of swallowing biomechanics and bolus flow during feeding of various volumes and bolus textures
        • Requires exposure to fluoroscopic radiation
      • Fiberoptic endoscopic evaluation of swallow r60c191
        • Direct observation of swallowing with a flexible nasopharyngolaryngoscope is an alternate or additional modality used to evaluate swallowing mechanics and risk for aspiration
        • Enables visualization of physiology of swallowing biomechanics and bolus flow during feeding
        • Avoids exposure to fluoroscopic radiation
      • Nasopharyngoscopy r4c192
        • Real-time direct visualization of the upper airway to the level of the vocal cords allows observation of motion during vocalization to assess soft tissue structures and the velopharyngeal sphincter function

    Functional testing

    • Pneumatic otoscopy r52c193
      • Subjective measurement of tympanic membrane mobility
      • Minimal or sluggish movement of the tympanic membrane indicates fluid in the middle ear suggesting otitis media with effusion
    • Tympanometry r52c194
      • Objective measure of tympanic membrane mobility
      • Flat tympanometry tracing is concerning for otitis media with effusion
    • Auditory brainstem response r55c195
      • Surface electrodes record neural activity generated in the cochlea, auditory nerve, and brainstem in response to acoustic stimuli delivered via an earphone
      • Measurements reflect the status of the peripheral auditory system, the eighth nerve, and the brainstem auditory pathway
    • Otoacoustic emissions r55c196
      • Probe with attached microphone placed in external ear canal records cochlear responses to acoustic stimuli
      • Measurements reflect the status of the peripheral auditory system extending to the cochlear outer hair cells

    Differential Diagnosis

    Most common

    • Premaxillary agenesis r8c197
      • Midline lip and alveolar ridge malformation that results from premaxillary agenesis may be mistaken for a median or midline cleft
      • A wide median malformation of the primary palate is a hallmark of the holoprosencephaly spectrum of brain malformation syndromes
      • True median or midline clefting of the primary palate is rare and often associated with a congenital syndrome
      • True median clefts are often subtle and isolated to the vermilion border but may extend to alveolar ridge
      • In contrast, midline malformations associated with premaxillary agenesis are often prominent and wide
      • Definitively diagnose by brain imaging showing additional midline brain abnormalities associated with premaxillary agenesis and holoprosencephaly spectrum of brain malformation syndromes c198

    Treatment

    Goals

    • Supportive care for neonates and infants with attention to feeding, nutrition, and protection of airway
    • Surgical repair of anatomy with goals to: r3
      • Improve cosmetic appearance
      • Allow normal feeding
      • Facilitate normal speech
      • Improve eustachian tube function and prevent otitis media
    • Monitor for complications

    Disposition

    Admission criteria

    Neonates and infants who develop failure to thrive require admission for monitoring and further diagnostic and treatment recommendations

    Neonates and infants in whom aspiration of feedings is of concern (eg, cyanosis, coughing, choking with feedings) require admission for observation and further diagnostic and treatment recommendations

    Neonates with concomitant Pierre Robin sequence require monitoring for airway obstruction

    Patients who undergo cleft palate corrective surgery require admission to the hospital for pain management, advancement of feedings, and monitoring for airway compromise

    Criteria for ICU admission
    • Patients with a predisposition for airway obstruction (eg, syndromic patients with micrognathia or hypotonia) require ICU admission for close observation and management

    Recommendations for specialist referral

    • Consult neonatology service for presence during delivery of any infant with a known orofacial cleft owing to risk of airway obstruction and possibility of additional associated congenital anomalies
    • All patients are cared for by an interdisciplinary team with experience in diagnosis and treatment of cleft lip and/or palate; craniofacial team may include: r61
      • Team nurse coordinator to ensure integrated case management, continuity of follow-up, and family support and education
      • Pediatrician or family practitioner to provide coordinated care and close monitoring of growth, hearing, and neurocognitive development
      • Lactation consultant for breast feeding advocacy; nutrition consultant and feeding team if needed for neonates and infants failing to thrive
      • Geneticist or dysmorphologist to evaluate for suspected genetic syndromes and evaluate for subtle dysmorphic features in all patients at time of diagnosis with parent approval
        • Definitive indications for complete genetic evaluation include: r61
          • Positive familial association with a genetic syndrome
          • Prenatal growth deficiency
          • Unexplained postnatal growth deficiency
          • Developmental delay or mental retardation
          • Associated major malformations and/or disorders
          • Associated minor malformations and/or disorders inconsistent with the genetic background
          • Family request
          • Recognized genetic diagnosis
      • Pediatric plastic surgeon at time of diagnosis to evaluate for repair of cleft lip defect, construction of intact palate, creation of soft palate muscle velopharyngeal function, alveolar bone grafting, and orthognathic surgery if indicated r3
      • Otolaryngologist evaluation at initial team evaluation or by 6 months in all patients to: r61
        • Treat middle ear disease and place tympanostomy tubes when indicated
        • Assist with advanced airways when necessary
        • Assist with syndromic ear malformations
        • Assist with complex nasal deformities and postoperative nasal complications
        • Perform tonsillectomy and adenoidectomy when necessary
        • Evaluate and treat obstructive sleep apnea when indicated clinically
      • Audiologists to address hearing deficiency due to conductive and/or sensorineural hearing loss r52
      • Speech-language pathologist for diagnosis and nonsurgical treatment of velopharyngeal insufficiency, presurgery planning, and speech therapy r4
      • Pediatric dentistry is required in all patients within 6 months of the first tooth eruption for dental examinations; caries control; and preventive, restorative, and prosthetic dental treatment as needed r62
      • Orthodontist is required for treatment recommendations to achieve functional and acceptable esthetic occlusion and facial harmony beginning in infancy
      • Psychiatrist, psychologist, and/or social worker are required beginning at the time of diagnosis to address psychosocial coping mechanisms and stressors in patients and families
      • Refer the following patients for genetic counseling to evaluate and discuss risks of orofacial congenital anomalies in future children:
        • Parents of a child with cleft lip and/or palate
        • Patients with a family history of cleft lip and/or palate
        • Adolescents with cleft lip and/or palate

    Treatment Options

    Extensive multidisciplinary care is often required for patients with orofacial clefting r10

    • Specialized and individualized care is frequently required during the neonatal period extending through childhood and routinely into adulthood
      • Type of services required and timing of services are largely dependent on:
        • Type and severity of orofacial clefting
        • Presence of additional associated congenital anomalies and congenital syndrome
    • Care often includes feeding assistance; counseling; plastic and reconstructive surgery; orthodontics; dental care; and otolaryngology, speech, audiology, psychosocial, and developmental follow-up

    Immediate concerns for infants with cleft palate with or without cleft lip include attention to patient's ability to maintain airway patency and ability to feed r13

    • Airway support
      • Some infants require prone positioning, a nasal airway, or other airway adjuncts to maintain airway patency
      • Patients with a concomitant syndrome (eg, Pierre Robin sequence) may require more definitive airway protection (eg, tongue-lip adhesion, mandibular distraction osteogenesis, tracheotomy)
    • Specialized feeding r63
      • Often requires specific feeding techniques in consultation with feeding nurse or team
      • Specialized strategies may include:
        • Unconventional positioning during breast and bottle-feeding (eg, upright)
        • Frequent suctioning of nasal passage during feeding with bulb syringe
        • Specialized nipples and bottles
        • High-calorie formula supplementation
        • Use of oropharyngeal appliance to separate oral and nasal cavity is not routine r5r63
          • May be used despite limited evidence to support benefit with feeding in most patients
      • Less commonly, infants require more invasive feeding techniques (eg, use of a nasogastric tube)

    Surgical repair of orofacial clefting r61

    • Surgical closure is necessary to achieve normal appearance, allow for normal feeding, facilitate normal speech, and minimize complications (eg, psychological problems, hearing loss, otalgia, dental complications)
    • Closure of cleft lip and palate requires a series of operations in infancy
    • As patient approaches adulthood, additional surgical procedures involving lip, nose, palate, and jaw may be required, depending on type and severity of malformation r61
    • Use of presurgical dental orthopedic and nasoalveolar molding appliances is dependent on the interdisciplinary cleft team and may be recommended r2r5r61
    • Timing of surgical repair and technique is individualized r5
      • Cleft lip r13
        • Primary surgery aims at creating normal anatomy and functionality
        • Surgical repair of the cleft lip is usually initiated within the first 6-12 months of life and may be performed as early as is considered safe for the infant r46r61
        • Prior to surgery, maxillary orthopedics may be indicated for some infants r61
        • Surgical correction of the cleft nasal deformity may be performed during primary surgery; definitive rhinoplasty is performed at time of skeletal maturity
        • Defects in alveolar ridge are repaired with bone grafting later in childhood
      • Cleft palate
        • Primary palatoplasty aims at creating normal swallowing physiology and promoting normal speech r5
        • Timing of procedure is variable r5
          • In the typically developing child, the cleft palate should be closed by the age of 18 months, though preferably earlier when possible r61
            • Early closure may increase risk of distorted facial growth; late closure may result in increased risk for speech distortion r13
            • Both hard and soft palate should be closed during the first year of life if optimal speech development is desired r46
              • However, later repair of the hard palate allows optimal maxillary growth
        • No single standardized procedure exists; specific repair is individualized and dependent on degree and type of specific malformation r3
          • The von Langenbeck or Bardach 2-flap techniques accompanied by an intravelar veloplasty are commonly used for complete cleft repair
          • Furlow double-opposing Z-plasty is frequently used for isolated soft palate clefts, submucous cleft palate, and soft palate and/or hard palate repair r2
      • Velopharyngeal incompetence
        • Surgical pharyngeal flap procedure or pharyngoplasty may be required to reposition pharyngeal muscles to correct velopharyngeal incompetence r5
        • Potential indications include speech deficits recalcitrant to speech and language therapy in older toddlers r5

    Nondrug and supportive care

    Newborn and infant feeding r63

    • Encourage breastfeeding or bottle-feeding breast milk when possible r50c199c200
      • Breast milk has numerous benefits, including protection against chronic otitis media, which is common in patients with cleft palate
    • Use techniques recommended in consultation with feeding team or lactation consultant c201
    • Feeding for neonates and infants with cleft lip r63c202
      • Unilateral cleft lip alone typically does not cause serious feeding impairment r50
        • Special techniques may include holding infant so cleft is oriented toward the top of breast and occluding cleft with mother's finger r50
      • Bilateral cleft lip may pose more difficulties in feeding
        • Upright, face-on, straddle positioning may facilitate flow and prevent choking when breastfeeding r50
        • Dancer hand position (ie, apply support to both the breast and the infant's chin and jaw) may be effective r63
    • Feeding for neonates and infants with cleft palate r63
      • Infants with small cleft of the soft palate may produce enough suction to breastfeed successfully r50
      • Infants with larger cleft may be unable to successfully breastfeed owing to nasal reflux and inability to create suction on nipple or transfer milk effectively; a special feeding device is usually needed r64
      • Specialized feeding strategies may include: r63
        • Semiupright positioning may reduce nasal and eustachian tube reflux r50
        • Additional specialized positioning and support during breastfeeding c203
          • Football hold (body of infant positioned alongside mother instead of across lap) may be more effective than traditional cross-cradle breastfeeding position r50
          • Position breast toward the side of palate with most intact bone to facilitate compression and reduce nipple being pushed into cleft r50
          • Apply gentle pressure to cheek to minimize the cleft or turn the cleft side toward the breast to minimize cleft r50
          • Support infant's chin to stabilize the jaw during sucking r50
          • Manual expression of breast milk to compensate for diminished suction r50
        • Minimize aerophagia
          • Advise frequent burping and slow feeding r13
        • Specialized bottles and nipples r63
          • Soft, squeezable bottles may facilitate flow r65
          • Crosscut or Y-cut openings in the nipple may facilitate flow
          • Elongated nipples may help to occlude cleft opening in the palate
          • Other strategies include use of Habermann feeder, pigeon feeder, and bulb syringe assistance r3r64
      • Infants may require supplemental feedings for adequate growth and nutrition r50c204
      • Nasogastric feedings are rarely required

    Dental care c205

    • Ongoing specialized dental care is required throughout life and is integral to treatment process r66
    • Establish pediatric dental home within 6 months of eruption of first tooth and no later than 1 year of age r66
    • Pediatric and adult dentists provide a dental home and coordinate services in consultation with orthodontists, cleft surgeons, and prosthodontic specialists
    • Other roles of dentist include
      • Diligent caries control and periodontal disease management
      • Individualized imaging and dental model acquisition to evaluate dental and facial development
      • Assist with appropriate restorative care, dental spacing measures, and malocclusion treatment
      • Assist with creation of prosthetic devices (eg, obturation of palatal fissure, prosthetic speech devices) in select patients

    Orthodontic care c206

    • Orthodontic evaluation for ongoing treatment needs is necessary from infancy through adulthood r67
    • Treatment may be necessary for all 3 phases of dental eruption (ie, primary, mixed, and permanent dentition) r66
      • Staged orthodontic treatment followed by periods of retention and observation is preferred r66
    • Alveolar bone grafting into the alveolar cleft site r68c207
      • Before eruption of permanent teeth, construction of missing alveolar ridge is often required
    • Protraction headgear r68c208
      • May be required during mixed dentition years to modify and redirect the nasomaxillary complex r69
    • Orthognathic surgery may be indicated in skeletal imbalances of mandible and maxilla r66r70c209c210
      • A Le Fort 1 osteotomy, alone or in combination with a setback osteotomy of the mandible, corrects sagittal jaw discrepancy that cannot be resolved by orthodontic treatment alone r46
      • Distraction osteogenesis is an option only for large sagittal discrepancies r46

    Tympanostomy tubes c211

    • Required for many patients owing to high rate of persistent otitis media with effusion associated with cleft palate r52
    • Tympanostomy tubes are often inserted at the time of first surgery in infants with cleft palate because of predilection for otitis media with effusion r1r13

    Speech and language therapy r5c212c213

    • Early intervention during babbling phase is recommended to counteract adverse speech development r5
    • Indications for early intervention include:
      • Infants with cleft palate r5
      • Deficiencies detected on prelinguistic speech-language assessment around 6 months of age r61
    • In older children, direct imaging of the larynx may be needed to define velar function r61c214
    • Secondary speech surgery may be required to treat persistent velopharyngeal incompetence r5c215

    Psychological assessment and support r61c216c217

    • Both patient and caregivers need to be assessed regularly and referred to appropriate counseling or assistance, if necessary r61
    • Caregivers
      • Regularly assess for parental competence and nurturance, child-management skills, and parent-child relationship r62
      • Offer counseling for problems including behavior management, teasing, rejection by other family members, public attitudes, fear of and expectations of surgical procedures, and emotional adaptation to treatment r61
      • Offer social skills training to cope with stress, and facilitate meeting other families caring for patients with craniofacial anomalies r61
    • Patient
      • Regularly assess emotional and behavioral adjustment of the child as well as assess cognitive development r61c218c219c220

    Genetic evaluation and counseling services offered to the family of a patient with orofacial clefting include: r61c221c222

    • Diagnosis and assessment of syndromes r61
    • Counseling regarding recurrence risk r61
    • Counseling regarding prognosis r61
    Procedures
    Cheiloplasty and repair of primary palate r13c223c224c225c226
    General explanation
    • Cheiloplasty aims to close the lip malformation and restore integrity of the orbicularis oris muscle
    • Unilateral clefts
      • Millard rotation-advancement technique or 1 of its variants is often used r13
        • Uses rotating flaps to provide a tension-free upper lip r13
      • Fisher anatomic subunit technique and triangular flap repair are other common cleft lip procedures r2
    • Bilateral cleft lips
      • Often repaired with straight line technique to achieve symmetry
      • Presurgical orthopedic manipulation (eg, dental plate, lip strapping, nasoalveolar molding) may be required with significant alveolar malformations r5r13
    • Primary tip rhinoplasty is usually performed during cheiloplasty r13
      • Revision of nose and/or lip may be required in adolescence
    • Clefting of the maxillary alveolar process is often repaired between ages 6 and 9 years, depending on dental development r1
      • Requires use of autogenous bone grafting to unite segments of maxilla
    Indication
    • Repair is typically performed around age 3 months r13
      • May be performed as early as 6 weeks old r3
    • Established oronasal fistula r1
      • Nasal floor repair is incorporated with the primary lip surgery
    Contraindications
    • Rule of over 10 is usually recommended for the timing of the cheiloplasty r13
      • Weight of at least 10 pounds (4.53 kg) r13
      • Hemoglobin count of 10 g/dL or more r13
      • Leukocytes less than 10,000/μL r13
      • Age older than 10 weeks r13
    Complications
    • Visible muscle bulge indicative of incomplete orbicularis oris repair r2
    • Minor complications in cosmetic appearance such as: r2
      • Notch at the vermilion-cutaneous junction
      • Misalignment of the median notch of the upper lip vermilion (Cupid's bow)
      • Scar contracture resulting in mucosal imbalance
    • Secondary procedure necessary to improve results is common r2
    Palatoplasty and repair of secondary palate r3c227c228
    General explanation
    • Procedure aims to close palatal malformation and separate oral cavity from nasal cavity, establish velopharyngeal function, and improve eustachian tube function while minimizing possible disturbance to facial growth r2
      • Soft palate musculature is reoriented to create an intact muscular ring, which is necessary for speech
    • Several techniques are available for primary closure of the cleft palate
      • Furlow technique uses double opposing Z-plasty technique of the soft palate and 2-layer closure of the hard palate
      • Von Langenbeck and Bardach repairs use 2-layer closure of the hard and soft palate and include levator muscle repositioning to create a muscular sling for velopharyngeal closure
    • Final outcome of palatal repair improves teeth alignment and feeding, prevents or reduces incidence of otitis media, and leads to competent speech
    • Pharyngeal flap procedure or pharyngoplasty to correct persistent velopharyngeal insufficiency is required in a minority of patients between ages 3 and 5 years r1
    • Some patients require some form of orthognathic surgical correction (eg, maxillary anterior advancement, distraction osteogenesis) secondary to maxillary hypoplasia in adolescence r5
    Indication
    • Typically performed between ages 9 and 12 months r1
    • Timing for cleft palate repair r13
      • Primary closure in otherwise normally developing child is recommended by 18 months of age r61c229
      • Single-stage repair is used to avoid persistent velopharyngeal insufficiency and delayed language development r13
        • Complete repair of both soft and hard palate is often performed between 9 and 12 months r13c230c231
      • 2-stage repair can be used in very wide cleft defects r13
        • Soft palate is repaired between ages 3 and 8 months r13c232
        • Hard palate is repaired between ages 15 months and 15 years r13c233
    Complications
    • Respiratory compromise r13
      • Caused by postoperative edema or excessive sedation
    • Oronasal or palatal fistulae r13
      • Develops in 3.4% to 29% of patients r13r71
      • Caused by excessive tissue tension or as a result of infection
      • Requires secondary procedure for closure
    • Persistent velopharyngeal insufficiency
      • About one-third of patients experience some degree of persistent hypernasality following primary palatoplasty r3r71
      • Symptoms may improve over time without need for secondary procedure r71
        • Pharyngeal flap procedure or sphincter pharyngoplasty to correct persistent velopharyngeal insufficiency is required in a minority of patients between ages 3 and 5 years r1
    • Maxillary growth restriction
      • May be caused by postoperative subperiosteal scarring
      • May require secondary orthognathic surgery (maxillary advancement) or distraction osteogenesis in adolescence r1

    Comorbidities

    • Patients with comorbid congenital syndromes may require individualized and specialized care throughout various treatment phases in consultation with treatment team
    • Patients with propensity for airway obstruction require a heightened level of monitoring at a tertiary care center and specialized pre- and postoperative management r13
      • These may include patients with micrognathia (eg, Pierre Robin sequence), patients with hypotonia (eg, Down syndrome), and patients with glossoptosis c234c235c236c237
      • Specialized care may include use of prone positioning, tongue-lip adhesion, mandibular distraction, nasal airway, and tracheotomy c238c239c240c241

    Monitoring

    • Weekly assessment of nutritional intake and weight gain during the neonatal period r61c242c243
    • Monitoring of infants and children is best done by a certified cleft team in conjunction with the patient's primary care physician and may include:
      • Monitoring weight gain and growth for failure to thrive r61c244
      • Monitoring motor, cognitive, and social development r61c245c246c247c248c249c250
      • Regular monitoring of speech and language development, with the possible exception of patients with cleft lip alone r61
      • Regular otologic and audiologic assessments (eg, tympanometry, pneumatic otoscopy, age-appropriate hearing assessments) r61c251c252c253c254c255c256
      • Regular dental and orthodontic follow-up r13c257c258c259c260
      • Monitoring parent-child relationship and parental coping skills and strategies r61c261c262
      • Regular follow-up by surgical specialists r13c263c264
      • Regular review of comprehensive treatment plan with caregivers and treatment team
        • Discuss need for modification in treatment plan when clinically indicated c265c266
        • Monitor need for more comprehensive genetic and/or further dysmorphology assessments; some complex syndromes involving craniofacial abnormalities may not be fully recognized until later childhood r61c267c268

    Complications and Prognosis

    Complications

    • Failure to thrive c269
      • May result from inadequate caloric intake, primarily in patients with cleft palate
      • Uncommonly requires more invasive techniques to maintain adequate caloric intake (eg, nasogastric feedings, gastric feeding tube)
    • Auditory complications
      • Hearing loss r52
        • Conductive hearing loss secondary to eustachian tube dysfunction that results in chronic otitis media with effusion is common in patients with cleft palate c270
        • Sensorineural hearing loss accompanies many syndromes associated with cleft lip and palate c271
      • Otitis media and otalgia
        • Abnormal positioning of palatal musculature causes eustachian tube dysfunction r64c272
        • Recurrent acute otitis media and chronic otitis media with effusion are very common in patients with cleft palate r52r72c273c274
          • Corrective palatoplasty reduces but does not eliminate risk
          • Children with occult submucous cleft palate often present with recurrent otitis media with effusion r52
        • Otalgia associated with chronic otitis media and recurrent acute otitis can occur r3c275c276
      • Cholesteatoma c277
        • Secondary to recurrent or persistent otitis media r5
    • Speech problems
      • Velopharyngeal insufficiency (ie, inability to close off nasopharynx with soft palate during speech)r1 is common in patients with cleft palate r4c278
        • Results in hypernasal speech and articulation errors r1c279c280
        • About one-third of patients show some degree of hypernasality after primary cleft palate surgery r71
          • A minority of patients require secondary pharyngeal flap procedure or pharyngoplasty to correct velopharyngeal insufficiency r71
      • Additional associated hearing loss increases speech difficulty in many children c281
    • Airway obstruction
      • Obstructive sleep apnea c282
        • Higher rates of sleep apnea occur in patients with cleft palate r1
        • Cause is multifactorial (eg, inferiorly positioned hyoid bone, maxillary hypoplasia, palatal and pharyngeal muscle dysfunction, syndromic conditions such as Pierre Robin sequence)
    • Oronasal fistula c283
      • Persistent or recurrent oronasal fistulas may present days to years after palatal repair r1
      • Result from failure in palate repair
      • Lead to speech problems and flow of liquid or solid food into the nose when eating
      • Usually requires corrective surgery at some point
    • Dental complications
      • Dental malformations
        • Clefting of the primary palate
          • May be associated with congenital anomalies in the primary and secondary dentition (eg, deformed teeth, supernumerary teeth, congenital absence of teeth), particularly when the alveolar ridge is involved c284c285c286
        • Clefting of the secondary palate alone r1
          • Does not typically result in congenital anomalies of the primary and secondary dentition
      • Maxillary growth restriction
        • May follow palatoplasty in some patients and result in varying degrees of maxillary hypoplasia c287
        • Certain techniques of hard palate repair leading to greater area of denuded maxillary bone are associated with increased risk of maxillary growth restriction r1
      • Orthodontic complications affecting permanent dentition may include:
        • Posterior crossbites can manifest as single tooth to total segment involvement c288c289
        • Maxillary incisor rotations c290
        • Significant arch asymmetry and deviations from maxillary dental midline c291c292
      • Enamel hypoplasia r64c293
      • Predisposition to dental caries r64c294
    • Psychological problems
      • Many patients experience difficulty coping with stress related to issues of differing self-perception compared with peers r73c295
      • About one-fourth of patients aged 7 to 12 years show social and behavioral inhibition r73c296c297
      • Other problems encountered may include low self-concept and self-esteem, and depression c298c299c300
    • Learning disabilities
      • Difficulties in verbal expression and reading comprehension are occasional r74c301c302c303c304
      • Learning difficulties, when present and not associated with a syndrome, are likely a consequence of hearing loss and subsequent language deficiency r74c305
      • Overall, IQ scores of children with cleft lip and palate without an associated syndrome are within the average range r74

    Prognosis

    • Prognosis is highly dependent on type and degree of orofacial cleft and affected by the presence of other associated congenital anomalies or syndromes
    • For infants with isolated cleft lip and palate, survival rate is 97.7%; overall survival is approximately 77% when cleft lip and palate is associated with multiple congenital anomalies and 40% when associated with genetic or chromosomal syndromes r75
    • Long-term successful outcome requires management by a multidisciplinary team, including skilled surgeon
    • Surgery has an excellent success rate as the primary treatment to achieve normal facial anatomy, feeding ability, and reduce hearing and speech impairment r76
    • The majority of children with cleft lip and/or palate function according to their age; parental support and acceptance can help overcome social inhibition and low self-esteem r73

    Screening and Prevention

    Screening

    At-risk populations

    • Patients with risk factors are at increased risk; may include:
      • Positive family history of orofacial clefting r8
      • Native American and Asian ethnicity for cleft lip r3
      • Male children for cleft lip
      • Gestational exposure to cigarette smoke, alcohol, and certain medications r13
      • Children born from mothers with insufficient intake of folic acid during pregnancy r13

    Screening tests

    • Antenatal ultrasonography can detect 25% of cleft lips; cleft palate alone is difficult to detect in utero by routine transabdominal antenatal ultrasonography r5c306
    • Perform universal newborn screening with a complete examination of hard and soft palate in the newborn nursery and at initial newborn office visit r77c307
      • Visualize complete length of palate with an adequate light source while using a tongue depressor

    Prevention

    • The risk for noninheritable cleft lip or palate can be reduced by: r20
      • Avoidance of smoking and alcohol consumption during pregnancy c308c309
      • Avoidance of certain medications (eg, antiseizure, retinoids, folic acid antagonists) c310c311c312
      • Use of prenatal multivitamin containing 400 mcg of folic acid daily r8r64c313
        • May be associated with an up to 25% reduction in prevalence of orofacial clefting r20
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