Cleft Lip and Palate

1. Clinical Overview

Summary

Cleft Lip and/or Palate (CLP) represents the most common congenital craniofacial anomaly, arising from failure of fusion of the facial prominences during embryogenesis between weeks 4-12 of gestation. [1] The defect manifests as a discontinuity in the upper lip (cheiloschisis), alveolar ridge, and/or palate (palatoschisis), ranging from a minor notch to complete bilateral clefting affecting the primary and secondary palate.

The condition extends far beyond cosmetic concern, with profound functional implications for airway patency, feeding mechanics, Eustachian tube function, speech development, dental occlusion, and psychosocial wellbeing. [2] Management necessitates a longitudinal multidisciplinary team (MDT) approach from birth through adulthood, involving plastic surgeons, maxillofacial surgeons, ENT specialists, orthodontists, speech and language therapists, audiologists, specialist nurses, paediatricians, geneticists, and psychologists.

Key Facts

• Definition: Congenital discontinuity of the upper lip and/or palate due to failure of embryological fusion of facial prominences.
• Global Prevalence: 1 in 700 live births worldwide; significant ethnic variation exists. [3]
• Distribution: Cleft Lip with or without Palate (CL±P) comprises 70% of cases; Isolated Cleft Palate (CP) accounts for 30%. [1]
• Sex Predilection: CL±P is 2:1 male predominance; CP is 2:1 female predominance.
• Laterality: Left-sided clefts outnumber right-sided 2:1; bilateral clefts represent 20% of CL±P cases.
• Syndromic Association: Isolated CP has 50% syndrome association vs 15% for CL±P. [4]
• Timing: Lip fusion completes by week 6; palate fusion completes by week 12 of gestation.

Clinical Pearls

The Bifid Uvula Warning: Always inspect the uvula in newborn examinations. A bifid (split) uvula indicates a Submucous Cleft Palate in up to 80% of cases. The mucosa appears intact, but the underlying levator veli palatini muscles are disinserted. This causes velopharyngeal insufficiency often misdiagnosed as developmental delay or "lazy speech". [5]

Pierre Robin Sequence (PRS): The classic triad of Micrognathia + Glossoptosis + Cleft Palate (U-shaped) constitutes a neonatal airway emergency. Position these infants prone or lateral immediately; supine positioning allows tongue base obstruction. 70% of PRS cases respond to positional management alone. [6]

The Universal Glue Ear: Virtually 100% of children with cleft palate develop Otitis Media with Effusion (OME) due to Eustachian tube dysfunction from tensor veli palatini muscle abnormality. [7] Vigilant audiological surveillance is mandatory.

The 22q11 Connection: Approximately 70% of 22q11.2 deletion syndrome (DiGeorge/VCFS) patients have palatal anomalies. Any child with cleft palate plus cardiac defect, immunodeficiency, or hypocalcaemia warrants genetic testing.

Why This Matters Clinically

A cleft is not "fixed" by a single operation. It represents a 20-year journey requiring coordinated care from a specialist cleft team. The primary care physician plays a vital role in ensuring follow-up attendance, developmental surveillance, and early identification of complications such as conductive hearing loss, speech articulation disorders, and psychosocial difficulties including bullying and self-esteem issues.

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2. Epidemiology

Incidence and Prevalence

The global incidence of orofacial clefts demonstrates significant ethnic and geographic variation. [3]

Cleft Type Distribution

Laterality Distribution (CL±P)

The left-sided predominance relates to asymmetric embryological blood flow during facial prominence fusion. [8]

Recurrence Risk

Genetic counselling requires accurate recurrence risk estimation: [9]

Risk Factors

Environmental/Teratogenic Factors:

Protective Factors:

• Periconceptional folic acid (400μg daily): 25-50% reduction in CL±P risk. [11]
• Multivitamin supplementation: Additional modest protection.

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3. Aetiology and Pathophysiology

Embryological Development

Normal craniofacial development requires precise coordination of neural crest cell migration, proliferation, and fusion between gestational weeks 4-12. [12]

Week 4-5: Facial Prominence Formation

• Neural crest cells migrate from the neural tube to form five facial prominences:
  • Frontonasal prominence (1)
  • Paired maxillary prominences (2)
  • Paired mandibular prominences (2)

Week 5-6: Primary Palate and Lip Formation

• Maxillary prominences grow medially toward the medial nasal prominences
• Fusion creates the philtrum, primary palate (premaxilla), and central upper lip
• Failure of fusion → Cleft Lip (unilateral or bilateral)

Week 7-8: Secondary Palate Formation

• Palatal shelves (from maxillary prominences) initially hang vertically alongside the tongue
• Tongue drops inferiorly into the developing oral cavity
• Palatal shelves elevate and flip horizontally above the tongue

Week 9-12: Palatal Fusion

• Horizontal shelves fuse in the midline (anterior to posterior)
• Fusion with nasal septum superiorly
• Failure of fusion → Cleft Palate

Key Concept: Fusion requires physical contact. Any factor preventing shelf approximation (small shelves, persistent tongue elevation, timing disruption) results in clefting.

Molecular Pathophysiology

Exam Detail: Neural Crest Cell Signalling Pathways:

Multiple signalling cascades regulate facial prominence development: [12,13]

Key Genes Implicated in Non-Syndromic CLP:

Epigenetic Factors:

• DNA methylation patterns influenced by folate availability
• Maternal environmental exposures alter gene expression
• MicroRNA regulation of TGF-β pathways

Classification Systems

Kernahan Striped-Y Classification

The most widely used anatomical classification system: [14]

        1
       / \
      2   3
     /     \
    4       5
    |       |
    6       7
    |       |
    8       9

Affected segments are shaded on the diagram.

Veau Classification

LAHSHAL Notation

A descriptive system using anatomical abbreviations:

• L = Lip
• A = Alveolus
• H = Hard palate
• S = Soft palate

Capital letters = complete cleft; lowercase = incomplete cleft.

Example: LAHSHAL = Complete bilateral cleft lip and palate.

Functional Consequences of Clefting

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4. Clinical Presentation

Antenatal Diagnosis

Ultrasound Detection:

• Cleft Lip: Detected at 18-22 week anomaly scan with 75-93% sensitivity. [15]
• Cleft Palate: Rarely detected on routine 2D ultrasound (less than 25% sensitivity) due to acoustic shadowing.
• 3D/4D Ultrasound: Improved lip visualisation; palate remains difficult.
• MRI: Emerging role for fetal palate assessment in high-risk cases.

Antenatal Counselling Considerations:

• Parents should meet the cleft team before birth where possible.
• Information on feeding, surgery timeline, and long-term outcomes.
• Referral for genetic counselling if syndromic features suspected.
• Warning that normal scan does NOT exclude cleft palate.

Postnatal Presentation

Cleft Lip (Visible Defect):

Cleft Palate (May be Occult):

Feeding Difficulties

Feeding problems are the first functional concern and major source of parental stress: [2]

Pathophysiology of Feeding Failure:

• Cleft palate prevents generation of negative intraoral pressure (suction)
• Oral-nasal communication causes nasal regurgitation
• Inefficient suck-swallow-breathe coordination
• Increased energy expenditure; fatigue during feeds

Clinical Signs:

• Feeding duration > 30 minutes per feed
• Milk escaping from nose (nasal regurgitation)
• Choking, coughing, spluttering during feeds
• Excessive air swallowing; aerophagia
• Weight loss > 10% by day 5
• Failure to regain birth weight by 2 weeks

Pierre Robin Sequence (PRS)

A clinical triad with airway emergency potential: [6]

The Triad:

1. Micrognathia: Mandible is hypoplastic
2. Glossoptosis: Tongue falls posteriorly (no mandibular support)
3. Cleft Palate: U-shaped (wide), secondary to tongue obstruction during fusion

Airway Obstruction Signs:

• Inspiratory stridor
• Suprasternal/subcostal recession
• Cyanosis during feeds or sleep
• Apnoea episodes
• Failure to thrive (caloric deficit from work of breathing)

Severity Grading (Cole Classification):

Examination Checklist

Systematic Examination for Cleft Assessment:

Face:

• Lip: Unilateral/bilateral; complete/incomplete
• Nose: Alar deformity; columella deviation; nasal floor defect
• Philtrum: Disruption of vermillion border and Cupid's bow

Intraoral:

• Alveolus: Gap in gum ridge; premaxillary position
• Hard Palate: Extent of cleft; width
• Soft Palate: Involvement of velum
• Uvula: Bifid (submucous cleft indicator)
• Palpation: Posterior hard palate notch (submucous cleft)

Syndromic Features Screen:

• Ears: Position, shape, pits (preauricular)
• Eyes: Hypertelorism; coloboma; palpebral fissure slant
• Hands: Digit anomalies
• Heart: Murmurs (22q11.2)
• General: Dysmorphism; growth parameters

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5. Investigations

Neonatal Workup

Genetic Testing Indications

Strong Indications:

• Isolated cleft palate (50% syndromic)
• Any cleft + cardiac defect
• Multiple congenital anomalies
• Family history of known syndrome
• Dysmorphic features

Genetic Panel Approach:

Audiological Assessment

Mandatory for all cleft palate patients: [7]

Tympanometry Findings:

• Type B (flat): Middle ear effusion (OME)
• Type C: Negative middle ear pressure (Eustachian dysfunction)

Speech and Language Assessment

Formal assessment commences at 18 months with ongoing surveillance: [16]

Velopharyngeal Function Assessment

When VPI is suspected (hypernasality, nasal emission, compensatory articulation):

VP Closure Patterns (Nasendoscopy):

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6. Associated Syndromes

Approximately 30% of all clefts and 50% of isolated cleft palate are associated with recognised syndromes: [4]

Common Syndromic Associations

Red Flags Suggesting Syndromic Cleft

• Isolated cleft palate (especially submucous)
• Cardiac murmur or anomaly
• Ear anomalies (microtia, pits, low-set)
• Digital anomalies
• Growth failure beyond feeding difficulty
• Global developmental delay
• Family history of multiple affected generations

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7. Management

Multidisciplinary Team (MDT) Structure

The centralised cleft MDT model demonstrates superior outcomes compared to isolated care: [17]

Core Team Members:

Extended Team:

• Maxillofacial prosthodontist
• Oral surgeon
• Paediatric dentist
• Social worker
• Dietitian

Feeding Management

Immediate Neonatal Priorities: [2]

1. Assessment by Cleft Nurse within 24 hours
2. Feeding method determination:
   • Cleft lip only: Breastfeeding often successful (breast tissue fills gap)
   • Cleft palate: Specialist bottle required (cannot generate suction)

Specialist Feeding Equipment:

Feeding Technique Principles:

• Upright position (45-60 degrees) to minimise nasal regurgitation
• Frequent burping every 15-30mL (excessive air swallowing)
• Limit feed duration to 30 minutes (beyond this, caloric expenditure exceeds intake)
• Monitor weight gain (minimum 20-30g/day)
• Nasogastric tube if weight loss persists despite optimisation

Troubleshooting Guide:

Presurgical Orthopaedics

Nasoalveolar Moulding (NAM):

• Custom acrylic plate with nasal stent
• Applied from 1-2 weeks of age until lip repair
• Aims to narrow alveolar gap and improve nasal cartilage position
• Reduces surgical complexity of bilateral repairs

Indications:

• Wide unilateral clefts (> 10mm gap)
• Bilateral cleft lip and palate
• Severely displaced premaxilla

Surgical Timeline: Staged Repair Protocol

The standard UK protocol follows evidence-based timing: [17,18]

The Rule of 10s (Lip Repair Readiness)

Traditional criteria for safe anaesthesia in infancy:

• 10 weeks of age
• 10 lbs (4.5 kg) weight
• 10 g/dL haemoglobin

Modern practice uses clinical readiness assessment rather than rigid numerical criteria.

Surgical Techniques

Primary Lip Repair (Cheiloplasty)

Unilateral Cleft Lip - Millard Rotation-Advancement Technique: [18]

Bilateral Cleft Lip - Modified Millard or Mulliken Technique:

• Central prolabium preserved
• Bilateral advancement of lateral lip elements
• Muscle reconstruction critical for lip animation
• Nasal tip correction; columella lengthening

Key Surgical Principles:

• Anatomical landmark preservation (Cupid's bow peak, white roll)
• Muscle functional reconstruction (not just skin closure)
• Nasal floor closure
• Minimal tension on closure

Primary Palate Repair (Palatoplasty)

Timing Considerations: [19]

• Earlier repair (6-9 months): Better speech outcomes
• Later repair (12-18 months): Less maxillary growth restriction
• Current consensus: 9-12 months balances both concerns

Techniques:

Exam Detail: Intravelar Veloplasty (Critical Component):

In cleft palate, the levator veli palatini muscles insert anomalously along the posterior hard palate edge rather than forming a transverse sling. Intravelar veloplasty involves:

1. Dissecting levator muscles from abnormal insertion
2. Repositioning muscles to transverse orientation
3. Suturing in midline to create functional "muscle sling"
4. This sling elevates the palate during speech to achieve velopharyngeal closure

Failure to perform adequate muscle repositioning is the primary cause of VPI post-repair.

Alveolar Bone Grafting (ABG)

Timing:

• Age 8-11 years (before canine eruption)
• Optimal when canine root is 1/2-2/3 formed on radiograph

Procedure:

• Donor site: Iliac crest (cancellous bone)
• Alternative: Tibial bone, mandibular symphysis
• Graft placed into alveolar cleft defect
• Allows canine eruption through graft

Outcomes:

• Success rate > 90% for bone integration
• Enables orthodontic treatment completion
• Provides periodontal support for adjacent teeth

Secondary Speech Surgery

When VPI persists despite adequate therapy:

Post-operative Monitoring:

• Risk of obstructive sleep apnoea (over-correction)
• Polysomnography if symptoms develop

Speech and Language Therapy

Goals by Age: [16]

VPI-Specific Therapy:

• Therapy can address compensatory articulation (glottal stops, pharyngeal fricatives)
• Therapy cannot correct structural VPI (requires surgery)

Home Exercises (Age 18 months - 4 years):

• "b"
• "t"
• "d" sounds in play | Oral pressure consonants |

ENT and Audiological Management

Otitis Media with Effusion (OME)

Prevalence: 90-100% of cleft palate children develop OME due to Eustachian tube dysfunction. [7]

Mechanism:

• Tensor veli palatini muscle dysfunction
• Abnormal muscle insertion into soft palate
• Inability to actively open Eustachian tube

Management Algorithm:

Grommet Insertion:

• Often performed at time of lip or palate repair
• May require multiple insertions (extrude after 9-12 months)
• Hearing aids for persistent loss unresponsive to grommets

Long-term Outlook:

• Eustachian tube function typically improves with age
• Most children cease requiring intervention by adolescence

Orthodontic Management

Staged Approach:

Common Dental Anomalies:

• Missing lateral incisor (in alveolar cleft)
• Supernumerary teeth
• Ectopic canine eruption
• Enamel hypoplasia
• Class III malocclusion (maxillary hypoplasia)

Orthognathic Surgery

Indication: Significant maxillary hypoplasia causing Class III skeletal relationship not correctable by orthodontics alone.

Timing: After skeletal maturity (16-18 years females; 18-21 years males)

Procedure:

• Le Fort I osteotomy with advancement
• Often combined with mandibular setback (BSSO)
• Genioplasty if indicated
• Distraction osteogenesis for severe cases

Outcomes:

• Improved occlusion and facial aesthetics
• Stability concerns (relapse rates higher in cleft patients)
• May improve VP function or cause VPI

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8. Complications

Feeding Complications

Hearing Complications

Speech Complications

Velopharyngeal Insufficiency (VPI)

Incidence: 20-30% post-palatoplasty require secondary surgery. [19]

Types of Speech Errors:

VPI Severity Grading:

Surgical Complications

Dental and Skeletal Complications

Psychosocial Complications

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9. Prognosis and Outcomes

Cosmetic Outcomes

Modern surgical techniques produce excellent aesthetic results: [18]

• Lip scar typically fades to fine line along philtral ridge
• Nasal symmetry improved but rarely perfect
• Secondary revision may be desired/needed in 15-30%
• Bilateral clefts more challenging for symmetry

Functional Outcomes

Speech:

• 70-80% achieve normal speech after primary repair. [19]
• 20-30% require secondary surgery or intensive therapy
• Compensatory articulation may persist even after VP correction

Hearing:

• Eustachian tube function improves with age
• Most have normal hearing by adolescence with appropriate intervention
• 5-10% have persistent hearing difficulties

Dental:

• Multiple orthodontic interventions typical
• Implants or prosthetics for missing teeth
• 25-50% require orthognathic surgery

Long-term Quality of Life

Studies demonstrate: [20]

• Adults with repaired cleft have good overall quality of life
• Some persistent concerns about appearance and speech
• Employment and relationship outcomes similar to general population
• Psychological support during childhood improves adult outcomes

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10. Prevention and Screening

Primary Prevention

Evidence-Based Interventions:

Antenatal Screening

Routine Ultrasound:

• 18-22 week anomaly scan includes facial views
• Cleft lip detection: 75-93% sensitivity
• Cleft palate detection: Poor (less than 25%)

High-Risk Screening:

• Previous affected child: Detailed ultrasound + counselling
• Positive family history: Genetic counselling; detailed scanning
• Teratogen exposure: Risk assessment; detailed scanning

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11. Psychosocial Considerations

Parental Impact

At Diagnosis:

• Grief reaction common ("loss of expected perfect baby")
• Guilt and self-blame (unfounded in most cases)
• Information overload; difficulty processing
• Immediate support from cleft nurse essential

First Year:

• Feeding stress and bonding challenges
• Surgical anxiety
• Sleep deprivation
• Impact on siblings and relationships

Ongoing:

• Multiple appointments; time off work
• Navigating school and social situations
• Advocacy role
• Financial burden

Child Development

Infancy:

• Feeding challenges may affect bonding (can be overcome with support)
• Hearing loss may impact early language if untreated
• Hospital experiences may cause separation anxiety

Pre-school:

• Speech differences may cause frustration
• Beginning awareness of visible difference
• Preparation for school important

School Age:

• Bullying and teasing common (30-50%)
• Academic impact if hearing loss unaddressed
• Absences for appointments may affect learning
• Self-esteem vulnerable

Adolescence:

• Appearance highly important; concerns intensify
• Dating and relationships
• Treatment fatigue; may refuse interventions
• Identity formation; "cleft identity" integration

Psychological Support Services

Embedded in MDT:

• Initial assessment and parental support
• Regular psychological screening (ages 5, 10, 16)
• Targeted intervention for identified difficulties
• Transition support to adult services

Interventions:

• Cognitive behavioural therapy for anxiety/depression
• Social skills training
• Assertiveness training (managing comments/questions)
• Family therapy if needed
• Peer support groups

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12. Clinical FAQs

Q: Did the mother cause this by something she did or ate? A: In the vast majority of cases, no specific cause is identified. Clefts result from complex gene-environment interactions largely beyond parental control. Parents should not blame themselves.

Q: Can babies with cleft palate breastfeed? A: Cleft lip only: Often successful as breast tissue fills the gap. Cleft palate: Usually not possible due to inability to create suction. Expressed breast milk via specialist bottle is an excellent alternative.

Q: Will my child have normal speech? A: 70-80% of children achieve normal speech after repair with appropriate therapy. The remaining 20-30% may need additional surgery or intensive therapy but most achieve intelligible speech.

Q: Will the scar be visible? A: Modern techniques place scars in natural lip contours (philtral column). Initially pink, scars fade over 1-2 years to a fine pale line. Revision is available if desired.

Q: Is this hereditary? Will future children be affected? A: Recurrence risk depends on family history. With one affected child and no affected parents, risk is approximately 4%. Genetic counselling provides personalised risk assessment.

Q: When can my child eat normally after surgery? A: After palate repair, soft diet for 4-6 weeks; avoid hard or crunchy foods that could traumatise the repair. Specialist bottle feeding resumes 1-2 days post-op (no breast or ordinary bottle for 4-6 weeks).

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13. Exam-Focused Content

Common Exam Questions

1. "What is the embryological basis of cleft lip versus cleft palate?"
2. "How would you manage a neonate with Pierre Robin Sequence and airway obstruction?"
3. "Describe the surgical management timeline for a child with unilateral cleft lip and palate."
4. "What are the causes and management of velopharyngeal insufficiency?"
5. "Why do children with cleft palate develop otitis media with effusion?"
6. "What is the role of alveolar bone grafting and when should it be performed?"
7. "Describe the multidisciplinary team involved in cleft care."

Viva Points

Viva Point: Opening Statement: "Cleft lip and palate is the most common congenital craniofacial anomaly, affecting approximately 1 in 700 live births. It results from failure of fusion of facial prominences during embryogenesis, with lip fusion completing by week 6 and palate fusion by week 12. The condition has significant functional implications for feeding, hearing, speech, and dental development, requiring longitudinal multidisciplinary management from birth to adulthood."

Key Facts to Mention:

• Epidemiology: 1:700; left > right > bilateral; male predominance for CL±P; female for CP
• Syndrome risk: 50% for isolated CP; 15% for CL±P
• Surgical timing: Lip at 3 months; Palate at 9-12 months; ABG at 8-11 years
• VPI rate: 20-30% post-repair
• OME: Universal in cleft palate; Eustachian tube dysfunction mechanism

Common Mistakes

❌ Mistakes that lose marks:

• Forgetting to examine for syndromic features
• Missing submucous cleft (always inspect and palpate palate)
• Not mentioning Pierre Robin as airway emergency
• Failing to discuss hearing surveillance for all cleft palate
• Confusing timing of lip vs palate repair
• Not knowing Eustachian tube dysfunction mechanism
• Describing therapy as treatment for structural VPI

Model Answers

Q: A newborn is diagnosed with bilateral cleft lip and palate. Outline your management approach.

A: "I would approach this systematically with immediate, short-term, and long-term considerations.

Immediately, I would ensure the airway is secure (particularly if Pierre Robin features are present), perform a feeding assessment with the cleft nurse specialist, and screen for syndromic features including cardiac examination, ear inspection, and general dysmorphology assessment.

In the first week, the baby should be registered with the regional cleft team, feeding established with specialist bottles such as the Haberman feeder, hearing screened, and genetic testing arranged if indicated by syndromic features.

The surgical timeline would be: presurgical nasoalveolar moulding if appropriate for the wide bilateral cleft, primary lip repair at around 3-6 months following the 'rule of 10s', grommets if OME is causing hearing loss, and palate repair at 9-12 months before speech development accelerates.

Ongoing MDT care includes speech therapy commencing at 18 months, regular audiology, orthodontic assessment from mixed dentition, alveolar bone grafting at 8-11 years, and psychological support throughout.

I would ensure parents understand this is a 20-year journey requiring coordinated multidisciplinary care, with excellent expected outcomes for most children."

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14. Key Guidelines

National and International Guidelines

Centralisation Evidence

The 1998 CSAG Report demonstrated that centralised high-volume cleft centres produce superior outcomes compared to dispersed low-volume services: [17]

• Improved surgical outcomes
• Better speech outcomes
• Reduced revision rates
• More comprehensive MDT care

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15. References

1. Mossey PA, Modell B. Epidemiology of oral clefts 2012: an international perspective. Front Oral Biol. 2012;16:1-18. doi:10.1159/000337464

2. Reid J. A review of feeding interventions for infants with cleft palate. Cleft Palate Craniofac J. 2004;41(3):268-278. doi:10.1597/02-148.1

3. Tanaka SA, Mahabir RC, Jupiter DC, Menezes JM. Updating the epidemiology of cleft lip with or without cleft palate. Plast Reconstr Surg. 2012;129(3):511e-518e. doi:10.1097/PRS.0b013e3182402dd1

4. Leslie EJ, Marazita ML. Genetics of cleft lip and cleft palate. Am J Med Genet C Semin Med Genet. 2013;163C(4):246-258. doi:10.1002/ajmg.c.31381

5. Reiter R, Brosch S, Wefel H, Schlömer G, Haase S. The submucous cleft palate: diagnosis and therapy. Int J Pediatr Otorhinolaryngol. 2011;75(1):85-88. doi:10.1016/j.ijporl.2010.10.015

6. Evans KN, Sie KC, Hopper RA, Glass RP, Hing AV, Cunningham ML. Robin sequence: from diagnosis to development of an effective management plan. Pediatrics. 2011;127(5):936-948. doi:10.1542/peds.2010-2615

7. Flynn T, Möller C, Jönsson R, Lohmander A. The high prevalence of otitis media with effusion in children with cleft lip and palate as compared to children without clefts. Int J Pediatr Otorhinolaryngol. 2009;73(10):1441-1446. doi:10.1016/j.ijporl.2009.07.015

8. Marazita ML. The evolution of human genetic studies of cleft lip and cleft palate. Annu Rev Genomics Hum Genet. 2012;13:263-283. doi:10.1146/annurev-genom-090711-163729

9. Sivertsen Å, Wilcox AJ, Skjærven R, et al. Familial risk of oral clefts by morphological type and severity: population based cohort study of first degree relatives. BMJ. 2008;336(7641):432-434. doi:10.1136/bmj.39458.563611.AE

10. Little J, Cardy A, Munger RG. Tobacco smoking and oral clefts: a meta-analysis. Bull World Health Organ. 2004;82(3):213-218. doi:10.1590/S0042-96862004000300011

11. Wehby GL, Murray JC. Folic acid and orofacial clefts: a review of the evidence. Oral Dis. 2010;16(1):11-19. doi:10.1111/j.1601-0825.2009.01587.x

12. Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate: understanding genetic and environmental influences. Nat Rev Genet. 2011;12(3):167-178. doi:10.1038/nrg2933

13. Jugessur A, Farlie PG, Kilpatrick N. The genetics of isolated orofacial clefts: from genotypes to subphenotypes. Oral Dis. 2009;15(7):437-453. doi:10.1111/j.1601-0825.2009.01577.x

14. Kernahan DA. The striped Y--a symbolic classification for cleft lip and palate. Plast Reconstr Surg. 1971;47(5):469-470. doi:10.1097/00006534-197105000-00010

15. Maarse W, Bergé SJ, Pistorius L, et al. Diagnostic accuracy of transabdominal ultrasound in detecting prenatal cleft lip and palate: a systematic review. Ultrasound Obstet Gynecol. 2010;35(4):495-502. doi:10.1002/uog.7527

16. Sell D, Harding A, Grunwell P. A screening assessment of cleft palate speech (GOS.SP.ASS). Eur J Disord Commun. 1994;29(1):1-15. doi:10.3109/13682829409041479

17. Sandy J, Williams A, Bearn D, Mildinhall S, Murphy T, Sell D, et al. Cleft lip and palate care in the United Kingdom--the Clinical Standards Advisory Group (CSAG) Study. Part 1: background and methodology. Cleft Palate Craniofac J. 2001;38(1):20-23. doi:10.1597/1545-1569_2001_038_0020_clapci_2.0.co_2

18. Fisher DM, Sommerlad BC. Cleft lip, cleft palate, and velopharyngeal insufficiency. Plast Reconstr Surg. 2011;128(4):342e-360e. doi:10.1097/PRS.0b013e3182268fab

19. Marrinan EM, LaBrie RA, Mulliken JB. Velopharyngeal function in nonsyndromic cleft palate: relevance of surgical technique, age at repair, and cleft type. Cleft Palate Craniofac J. 1998;35(2):95-100. doi:10.1597/1545-1569_1998_035_0095_vfincp_2.3.co_2

20. Stock NM, Feragen KB, Rumsey N. Adults' narratives of growing up with a cleft lip and/or palate: factors associated with psychological adjustment. Cleft Palate Craniofac J. 2016;53(2):222-239. doi:10.1597/14-269

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