Description

• Cleft lip
  • Deformity of the upper lip that may include a discontinuity of vermilion, skin, muscle, and mucosa as well as the underlying gingiva and bone
  • May be unilateral or bilateral
  • A complete cleft extends into the nose. An incomplete cleft has a bridge of intact tissue between the oral and nasal cavities.
• Cleft palate
  • May involve the gingiva, hard palate, and/or soft palate
  • Represents a visible separation between the two halves of the roof of the mouth, involving mucosa, muscle, and often the bones of the hard palate
  • A submucous cleft palate has intact mucosa, but the underlying muscle and bone are at least partially divided.

Epidemiology

• Incidence of cleft lip with or without cleft palate is approximately 1 in 700 births.
• Isolated cleft palate is present in 1 in 2,000 births across races.
• Racial heterogeneity noted in cleft lip and palate (Asians, 2.1 in 1,000 births; Caucasians, 1 in 1,000; African-Americans, 0.41 in 1,000)
• Gender heterogeneity noted in Caucasians (male-to-female ratio: cleft lip with or without cleft palate, 1.5 to 2:1; cleft palate only, 0.7:1)

Risk Factors

• Incidence of cleft lip with or without cleft palate increases with parental (especially paternal) age >30 years. Some association with low socioeconomic class may be nutrition-related.
• Some recognized patterns of malformation that include cleft lip and/or cleft palate may be caused by exposure to teratogens, but there is little evidence linking isolated clefts to exposure to any single teratogenic agent.
  • Exceptions include phenytoin (use during pregnancy has been associated with a 10-fold increase in the incidence of cleft lip) and isotretinoin (~26 relative risk of congenital malformations including cleft palate).
• Incidence of cleft lip in infants born to mothers who smoke during pregnancy is twice that in those born to nonsmoking mothers.

Pathophysiology

• Muscle fibers are atrophic and disorganized in the region of the cleft.
• Mitochondrial abnormalities are noted at the cleft margins by histochemical and electromyographic studies.

Etiology

• Cleft lip may result from failure of the medial nasal and maxillary processes to join in utero or possibly from lack of adequate mesenchymal reinforcement, leading to subsequent breakdown and separation.
• Cleft palate results from failure of the palatal shelves to fuse.
• Prenatal dietary supplementation with folic acid and vitamin B₆ has led to lower-than-expected incidence of cleft lip and cleft palate and to a decreased incidence of neural tube defects.
• Bilateral cleft lip is associated with cleft palate in 86% of cases. Unilateral cleft lip is associated with cleft palate in 68% of cases.
• Cleft lip/cleft palate is more common on the left, particularly in boys.

Commonly Associated Conditions

• Most clefts are nonsyndromic and may be either multifactorial in origin or the result of changes at a major single-gene locus.
• >400 genetic syndromes are associated with facial clefts.
• Among patients with clefts of the secondary palate alone, syndromes associated with microdeletions of chromosome 22q11.2 are currently the most common syndromic diagnoses.
  • Collectively known as 22q11.2 deletion syndrome, includes velocardiofacial syndrome, DiGeorge syndrome, and conotruncal anomaly face syndrome
  • Inheritance is autosomal dominant with considerable variability in phenotypic expression, which may include facial dysmorphism, developmental delay, cardiovascular anomalies, immunologic abnormalities, cleft palate, and velopharyngeal dysfunction.
• Next most common syndrome associated with palatal clefts is Stickler syndrome:
  • Characterized by autosomal dominance, cleft palate, epicanthal folds, flat facies, joint hyperflexibility, severe myopia, retinal detachment, and glaucoma
  • Caused by a mutation of the gene for type 2 collagen (chromosome 12q)
• Most common syndrome associated with clefts of the lip and/or palate is van der Woude syndrome (autosomal dominant, lower lip pits, IRF6 mutations, 1q32).
• Other genetic syndromes associated with cleft lip and/or palate:
  • CHARGE (coloboma of the eye, heart defects, atresia of the choanae, retardation of growth and/or development, genital and/or urinary abnormalities, and ear abnormalities and deafness) syndrome has an autosomal dominant pattern of malformation with majority of patients having CHD7 microdeletion or mutation.
  • Ectrodactyly–ectodermal dysplasia–cleft (EEC) syndrome is associated with p63 gene mutations.
  • Smith-Lemli-Opitz (defect in cholesterol synthesis, DHCR7 gene mutation, 7q34)
  • Pierre Robin sequence is a condition usually associated with a wide U-shaped cleft palate.
    • Characterized by a small mandible, retropositioned tongue, and subsequent upper airway obstruction
    • May occur in infants with or without genetic syndromes (Stickler most common)

History

• Prenatal exposure to alcohol, cigarettes, phenytoin, and isotretinoin
• Family history of cleft lip or cleft palate
• Speech problems in 1st-degree relative

Physical Exam

• Incomplete or complete cleft of lip, alveolus, hard and soft palate, or uvula. Soft palate and uvula clefts are always midline, whereas lip, alveolar, and hard palatal clefts can be unilateral or bilateral.
• A bifid uvula or a notch in the bone at the posterior hard palate may indicate a submucous cleft.
• A small mandible and retropositioned tongue may indicate a risk for airway obstruction (Pierre Robin sequence).
• Look for associated anomalies of the face, heart, and extremities that may indicate a clefting syndrome.
• Examination tips
  • Examine the palate from the top of the patient, with the head in your lap, using a tongue depressor and flashlight.
  • Palpate the posterior hard palate for a possible notch in the bone.
  • Palpate the gums and maxilla for a possible notch in the floor of the nose.

Diagnostic Tests and Interpretation

• Hearing evaluation
• Complete ophthalmologic examination to check for myopia, glaucoma, and retinal detachment and rule out Stickler syndrome
• Pulse oximetry to check for desaturation while feeding or while supine
• Polysomnography to distinguish central from obstructive apnea; increased serum 7-dehydrocholesterol and decreased serum cholesterol to rule out Smith-Lemli-Opitz syndrome
• Karyotype to rule out specific genetic abnormalities
• Fluorescence in situ hybridization to rule out a chromosome 22q11.2 deletion
• Echocardiography, renal ultrasound, and endocrine laboratory studies if indicated
• Prenatal diagnosis of cleft lip is reliable by ultrasound; prenatal diagnosis of cleft palate remains unreliable by ultrasound. 3D ultrasound has improved the reliability of prenatal diagnosis.
• Fetal MRI provides excellent soft tissue definition and can be used when the diagnosis is uncertain on ultrasound or to better delineate the severity of the cleft.
• After birth, no additional radiologic imaging is indicated in patients with isolated cleft lip and/or palate.

General Measures

• Airway management
  • Prone positioning if the tongue is causing airway obstruction
  • Plastic surgery and ENT consultation if airway obstruction persists
• Orthodontics
  • Preoperative orthodontics may include obturators to facilitate feeding and speech; nasoalveolar molding and lip taping to narrow the cleft and reshape the nose before lip repair; palatal expansion prior to bone grafting; conventional orthodontics including braces, maxillary appliances, prosthetic teeth, bridgework; and maxillary and/or mandibular distraction to advance the mid- or lower face.

Diagnostic Procedures/Other

• Significant airway obstruction and desaturation in the neonatal period refractory to prone positioning may indicate the need for a tongue–lip adhesion, release of the floor of the mouth musculature, mandibular distraction, or tracheostomy.
• Wide clefts of the lip may benefit from either nasoalveolar molding or preliminary lip adhesion at 2 to 3 months of age. Timing of definitive lip repair varies from 2 to 6 months of age.
• Palate repair is generally done at <1 year of age to decrease speech and language difficulties.
• Otitis media is more common with cleft palate, and bilateral myringotomy tubes can be inserted at the time of cleft repair.
• Correction of secondary deformities may include the following:
  • Lip scar revision
  • Cleft nasal deformity correction (infancy to adulthood)
  • Alveolar bone grafts (usually when permanent canines are erupting, age 6 to 10 years)
  • Pharyngoplasty for soft palate–velopharyngeal incompetence (childhood to adolescence)
  • Closure of palatal fistulas
  • Orthognathic surgery for severe jaw deformities (after facial growth is complete)

Inpatient Consideratons

• Admission criteria
  • Airway obstruction or severe feeding difficulties in the neonate
• Discharge criteria
  • Stable airway
  • Tolerating feedings
  • Pain controlled on an oral regimen

Follow-Up Recommendations

Multidisciplinary team for routine visits from infancy to adolescence:

• Pediatrician
• Plastic surgeon
• Speech pathologist
• Orthodontist
• Pediatric dentist
• Otolaryngologist
• Oral surgeon
• Psychologist
• Social worker
• Anthropologist (facial growth specialist)
• Geneticist
• Support groups

Diet

• Cleft patients may have significant feeding problems because of an inability to generate negative intraoral pressure necessary to feed efficiently.
• Preemie nipples with enlarged or cross-cut openings, or soft plastic squeezable bottles, can facilitate milk flow.
• Specially designed cleft bottles are commercially available.
• Poor weight gain may necessitate nasogastric tube feedings.

Prognosis

Very good. Most patients undergo normal growth and development. Long-term follow-up by a multidisciplinary team and parental support are critical for optimal outcomes.

Complications

• Airway obstruction and feeding disorders, particularly with Pierre Robin sequence
• Chronic otitis media
• Speech problems, including hypernasality and articulation errors
• Associated malformations
  • ~1/3 of patients with cleft palate has associated anomalies, with isolated cleft palates having the highest. CNS, cardiac and urinary tract malformations, and clubfoot are commonly associated with clefting.
• Potential problems
  • Hypernasal resonance and nasal air emission during speech may indicate velopharyngeal incompetence or palatal fistula. 8–30% of patients may require additional palatal or pharyngeal surgery following initial palate repair.
  • Multiple ear infections may require prolonged use of myringotomy tubes to prevent hearing impairment. Audiograms should be obtained regularly.
  • Delays in speech and language development may require detailed evaluation, early intervention programs, and speech therapy.
  • Poor dentition, occlusal problems (crossbite), gingivitis, and crowding
  • Learning disabilities are increased in children with clefts.
  • Behavior disorders and psychosocial adjustment disorders
  • ~25% of affected individuals will manifest maxillary hypoplasia that requires jaw surgery to correct occlusal abnormalities.

ICD-9

• 749.2 Cleft palate with cleft lip, unspecified
• 749.1 Cleft lip, unspecified
• 749 Cleft palate, unspecified
• 749.21 Cleft palate with cleft lip, unilateral, complete
• 749.02 Cleft palate, unilateral, incomplete
• 749.04 Cleft palate, bilateral, incomplete
• 749.24 Cleft palate with cleft lip, bilateral, incomplete
• 749.01 Cleft palate, unilateral, complete
• 749.12 Cleft lip, unilateral, incomplete
• 749.22 Cleft palate with cleft lip, unilateral, incomplete
• 749.23 Cleft palate with cleft lip, bilateral, complete
• 749.14 Cleft lip, bilateral, incomplete
• 749.03 Cleft palate, bilateral, complete
• 749.11 Cleft lip, unilateral, complete
• 749.13 Cleft lip, bilateral, complete

ICD-10

• Q37.9 Unspecified cleft palate with unilateral cleft lip
• Q36.9 Cleft lip, unilateral
• Q35.9 Cleft palate, unspecified
• Q37.5 Cleft hard and soft palate with unilateral cleft lip
• Q37.8 Unspecified cleft palate with bilateral cleft lip
• Q37.0 Cleft hard palate with bilateral cleft lip
• Q37.2 Cleft soft palate with bilateral cleft lip
• Q36.1 Cleft lip, median
• Q37.3 Cleft soft palate with unilateral cleft lip
• Q35.5 Cleft hard palate with cleft soft palate
• Q37.4 Cleft hard and soft palate with bilateral cleft lip
• Q35.1 Cleft hard palate
• Q35.3 Cleft soft palate
• Q37.1 Cleft hard palate with unilateral cleft lip
• Q36.0 Cleft lip, bilateral

SNOMED

• 66948001 Cleft palate with cleft lip (disorder)
• 80281008 Cleft lip (disorder)
• 87979003 Cleft palate (disorder)
• 204614006 Bilateral complete cleft palate with cleft lip (disorder)
• 80446009 Complete bilateral cleft lip (disorder)
• 204616008 Central complete cleft palate with cleft lip (disorder)
• 304068004 bilateral cleft lip (disorder)
• 253984004 Bilateral complete and incomplete cleft lip (disorder)
• 270513005 Central complete cleft palate (disorder)
• 268197001 Central incomplete cleft palate (disorder)
• 204617004 Central incomplete cleft palate with cleft lip (disorder)
• 47686007 Incomplete bilateral cleft palate (disorder)
• 24194000 Complete bilateral cleft palate (disorder)
• 204615007 Bilateral incomplete cleft palate with cleft lip (disorder)
• 62815003 Incomplete bilateral cleft lip (disorder)