DESCRIPTION

Cleft lip and/or cleft palate is a spectrum of anomalies and may include the following:

• Isolated cleft lip (CL): deformity of the upper lip that may include a discontinuity of vermillion, skin, muscle, and mucosa as well as the underlying gingiva and bone. Further classification includes:
  • Unilateral versus bilateral
  • Complete versus incomplete versus microform
    • Complete: disruption of the lip, nasal sill, and alveolus
    • Incomplete: Nasal sill remains intact.
    • Microform: vermillion notch, scar transgressing vertical length of the lip, vertical lip shortness; may include nasal defect
• Isolated cleft palate (CP): deformity of the palate that may include a discontinuity of gingiva, hard palate, and/or soft palate. Further classification includes:
  • Unilateral versus bilateral
  • Primary (disruption of the alveolus and anterior palate back to the incisive foramen) versus secondary (disruption from the incisive foramen back to the uvula)
• Cleft lip and palate (CLP)
• Submucous cleft: muscular diastasis of the velum; often have bifid uvula and notched posterior hard palate
  • Can be asymptomatic, although 15% will develop velopharyngeal insufficiency (VPI) resulting in speech difficulties

EPIDEMIOLOGY

• Incidence of cleft lip with or without cleft palate (CL ± P) is 1:700 births for all births (CLP 46%, CP 33%, CL 21%)
• Asians 1:500, European Americans 1:1,000, African Americans 1:2,000
• Unilateral 9 times more common than bilateral
• Gender heterogeneity (CLP males > females; CP females > males)

RISK FACTORS

• Teratogens
  • Phenytoin: intrauterine exposure associated with a 10-fold increase in CL
  • Smoking: intrauterine exposure doubles incidence of CL
  • Others (alcohol, anticonvulsants, retinoic acid): associated with malformation patterns that include CL±P but not directly related to isolated clefts
• Parental age: incidence CL±P increases with parental (especially paternal) age >30 years
• Socioeconomic status: incidence CL±P increases with lower socioeconomic status (SES) (may be nutrition-related)
• Genetics
  • 33% of patients with CL±P have a positive family history.
  • After one child with CL±P, 4% risk second child affected; after having two children with CL±P, 9% risk third child affected.
  • After one child with CP, 2% risk second child affected; after having two children with CP, 1% risk third child affected.
  • Syndromes
    • 10% infants with CLP have an associated syndrome.
    • 30% infants with CL have an associated syndrome.
    • 50% infants with CP have an associated syndrome.

ETIOLOGY

• Cleft of lip occurs when there is a failure of fusion of the medial nasal process and the maxillary process (typically by week 7 of gestation)
• Cleft of palate occurs when there is a failure of palatal shelves to fuse (typically by week 9 of gestation).

PATHOPHYSIOLOGY

• Feeding
  • CP causes difficulty creating negative intraoral pressure necessary to draw milk from nipple.
  • CL causes difficulty making a good seal around the nipple.
  • Specially designed cleft bottles available (squeezable or with valve)
• Hearing
  • Eustachian tube dysfunction is common in CP.
  • Associated with recurrent middle ear effusion and subsequent otitis media
• Dental: CP may cause occlusal abnormalities (crossbite), gingivitis, and crowding of teeth.
• Speech
  • CP or submucous cleft can cause inability to close velopharyngeal port, resulting in hypernasal speech.
  • Children with CP may also have speech and language development delays.
  • Some children may have excess scar tissue on their palates after palate repair that impairs speech.
• Cognitive: Learning disabilities are increased in children with clefts (likely related to neuropsychological deficits).
• Respiratory
  • Subsets of CL±P with associated conditions/syndromes (see below) may require management of other symptoms.
  • For example, patients with micrognathia may require close airway management and potential early surgical intervention prior to cleft repair.

COMMONLY ASSOCIATED CONDITIONS

Most CL±P are isolated conditions and not associated with syndromes. However, it is imperative to rule out syndromes/conditions that may be associated with CL±P.

• van der Woude syndrome (autosomal dominant)
  • Cleft association: CLP
  • Other phenotypic expression: lower lip pits
• Chromosome 22q microdeletions (autosomal dominant)
  • Velocardiofacial, DiGeorge, conotruncal anomaly
  • Cleft association: CP
  • Other phenotypic expression: facial dysmorphism, developmental delay, cardiovascular anomalies, immunologic anomalies, velopharyngeal dysfunction
• Stickler syndrome (autosomal dominant)
  • Cleft association: CP
  • Other phenotypic expression: epicanthal folds, flat facies, joint hyperflexibility, severe myopia, retinal detachment, glaucoma
• Pierre Robin sequence (autosomal dominant)
  • Cleft association: CP (secondary)
  • Other phenotypic expression: small mandible, retropositioned tongue, possible upper airway obstruction
• CHARGE syndrome (autosomal dominant)
  • Cleft association: CL±P
  • Other phenotypic expression: eye coloboma, heart defects, choanal atresia, growth/development retardation, genital/urinary anomalies, ear anomalies/deafness
• Smith-Lemli-Opitz (autosomal recessive)
  • Cleft association: CP
  • Other phenotypic expression: facial dysmorphism, microcephaly, intellectual disability, hypotonia, hypospadias, underdeveloped male genitalia, heart abnormalities, polydactyly, syndactyly

HISTORY

• Important to obtain a thorough prenatal history
  • Cleft lip is most often diagnosed in utero with routine ultrasound.
  • Cleft palate often not seen on ultrasound in utero, although 3D ultrasound has improved reliability.
  • Fetal MRI (not routinely done): very reliable; can delineate the severity of the cleft
• Document any risk factors (teratogens, family history, parental age, nutrition)

PHYSICAL EXAM

• Incomplete or complete cleft of lip, alveolus, primary and/or secondary palate, uvula
• Unilateral or bilateral cleft
• Look for associated anomalies of the face, heart, and extremities that may indicate a clefting syndrome.
• Examination tips
  • Place infant’s head in your lap and examine the palate from above; use tongue depressor and flashlight.
  • Palpate the gums and maxilla for a possible notch.

DIAGNOSTIC TESTS & INTERPRETATION

• Prenatal ultrasound/fetal MRI
• Isolated CL±P diagnosed by physical exam, no other tests indicated
• If there are concerns for commonly associated conditions, consider further imaging/diagnostic tests related to specific condition.

FOLLOW-UP RECOMMENDATIONS

Multidisciplinary team for routine visits from infancy through adolescence:

• Plastic surgeon
• Speech pathologist
• Orthodontist
• Pediatric dentist
• Otolaryngologist
• Oral surgeon
• Psychologist
• Social worker
• Geneticist
• Support groups

PROGNOSIS

• Very good, with most patients undergoing normal growth and development
• Early establishment and long-term follow-up by a multidisciplinary team and parental support are critical for optimal outcomes.

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