A common, non life-threatening abnormality which can have significant effect on maternal bonding. It may be associated with a syndrome (there are >150 of these) in 30% of all cleft lip and palate.

Epidemiology

Incidence

One of the most common congenital abnormalities with a worldwide incidence of 1.7 per 1000 live born babies.¹

• It is more common in Asian populations at 1.7/1000; American Indians 3.6/1000. Less common in African Americans - 0.4 per 1000.
• Cleft lip with or without cleft palate is most frequent in males.
• Cleft palate alone is found in 0.5/1000; females are more often affected than males.

Risk factors

There is a known risk in taking certain types of drugs during pregnancy, e.g. phenytoin, sodium valproate, benzodiazepines and corticosteroids.

• There may be a link to maternal smoking whereby the risks for clefts are increased among fetuses lacking enzymes involved in the detoxification of tobacco-derived chemicals.²
• Alcohol use, and specifically type, may also be a factor.³
• There is debate on the role of folic acid;^4,5 there may be dose dependency.⁶

Genetic factors

• If both parents are unaffected, but have one child with a cleft, the chance of the second child being similarly affected is 2-8%.
• If one or other parent has a cleft, the risk of a cleft in a child is 4-6% with each pregnancy.
• If the cleft is not associated with a syndrome, there is an associated gene; Interferon Regulatory Factor 6 gene variants can confer a risk for isolated cleft lip and palate. This can be identified in approximately 15% of patients.⁷

Recent genetic studies on human populations have demonstrated that nonsyndromic clefting has distinct genetic backgrounds which may then be revealed by environmental factors. Several loci (1 to 10) have been identified.⁸

Embryology

The lip has usually formed by 5-6 weeks of intrauterine life.⁹ The palate has formed by 10 weeks.
The cleft may be picked up by high resolution ultrasound at 20 weeks gestation.
Diagnosis is otherwise made after delivery.

Presentation

• Cleft lip may be unilateral or bilateral. The split runs from the edge of the philtrum to the margin of the nostril.
• Complete (extending through the length of the lip to the nose), or incomplete. The cleft is central in the palate.

Symptoms

Obvious gap in the newborn lip - usually the upper lip is affected.

Signs

Further inspection and palpation (there may be no defect in the mucosa covering the palate) of the roof of the mouth should reveal clefting of the hard and/or soft palate also.
The newborn may have difficulty feeding as a consequence of being unable to create a sufficient vacuum. However, most babies will be able to breast-feed.
There are special teats and bottles available to deliver the milk to the back of the throat, or a dental plate can be used to seal the roof of the mouth.
There may be associated poor weight gain, but they catch up by age 6 months.

Differential diagnosis

Mainly syndromal versus isolated.
Associated syndromes include:

• Apert's syndrome¹⁰
• Goldenhar syndrome¹¹
• DiGeorge's syndrome; this is underdevelopment of the third and fourth pharyngeal pouches. The syndrome is often associated with congenital heart defects, abnormalities of the large blood vessels around the heart, failure of the oesophageal tube to develop, abnormalities of facial structures, and of hypoparathyroidism. In most cases, there is a defect on chromosome 22.
• Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness) (CHARGE) syndrome¹²
• 3q29 microdeletion syndrome¹³
• Pierre Robin Sequence
• Trisomy 18 (Edwards' syndrome), Trisomy 13 (Patau's syndrome) and 15
• Van der Woude syndrome¹⁴

Investigations

Thorough physical examination of the neonate by a paediatrician to exclude presence of any associated syndrome.¹⁵Chromosome analysis may be required.

Associated diseases

• Females may have increased risk of breast cancer and primary brain malignancy.
• Males have increased risk of primary lung cancer.¹⁶
• Psychosocial problems may also be associated with clefting. None is major, but there may be behavioural problems, anxiety and depression.¹⁷ (There is a lack of good quality, uniform evidence on the subject).

Management

General measures

Ideally, patients should be managed by a multidisciplinary team which includes:
Plastic surgeons, maxillofacial surgeons; ENT, speech and language therapists, dentists, orthodontists, psychologists and specialist nurses. They will provide support and treatment until the child stops growing at around 18 years old.

Surgical

This is the bulk of the treatment. The absence of a sound evidence base for selection of treatment protocols is shown by a striking diversity of practices across Europe for surgical care of just one cleft subtype. A number of operations will be required as the child grows.

• Primary lip closure is performed at 3 months after birth, as long as weight and haemoglobin levels are adequate. Palate closure is performed at 6-12 months.
• Further operations are performed to improve appearance. If there is a gap in the gums, a bone graft may be required.

Recent advances in fetal (intrauterine) surgery using a fetal endoscopic technique, offer the exciting prospect for this condition of scarless wound healing, and bone healing without callus formation. There is also better or normal maxillary growth. As the technique improves, the outcome for mother and fetus is improving.¹⁸

Complications

• Chronic glue ear
• Hearing loss; the muscles of the palate affect the ear
• Dental cavities
• Displaced teeth
• Poor speech; the degree of problem is not related to the size of the defect. Speech is normally fine after repair, but may sound nasal.
• Lip deformity
• Nasal deformity

Prognosis

Treatment lasts over several years, but it is possible to achieve a normal appearance, and normal speech and eating habits.

Prevention

Identification of modifiable risk factors is the first step towards primary prevention. Such preventative efforts might involve manipulation of maternal lifestyle, improved diet, use of multivitamin and mineral supplements, avoidance of certain drugs and medicines and general awareness of social, occupational, and residential risk factors.¹Genetic counselling can identify high-risk families.

Historical notes

• Hippocrates and Galen both describe cleft lip in their works.
• Cleft palate was thought to be secondary to syphilis and not recognised as a congenital abnormality until 1556, nearly 2,000 years after Hippocrates. The first closure of a soft palate was in 1764 by a French dentist, Le Monier.
• The first hard palate closure was in 1834 by Dieffenbach.

Document references

1. Mossey PA, Little J, Munger RG, et al; Cleft lip and palate. Lancet. 2009 Nov 21;374(9703):1773-85. Epub 2009 Sep 9. [abstract]
2. Lammer EJ, Shaw GM, Iovannisci DM, et al; Maternal smoking, genetic variation of glutathione s-transferases, and risk for orofacial clefts. Epidemiology. 2005 Sep;16(5):698-701. [abstract]
3. Romitti PA, Sun L, Honein MA, et al; Maternal Periconceptional Alcohol Consumption and Risk of Orofacial Clefts. Am J Epidemiol. 2007 Jul 3;. [abstract]
4. Bille C, Knudsen LB, Christensen K; Changing lifestyles and oral clefts occurrence in Denmark. Cleft Palate Craniofac J. 2005 May;42(3):255-9. [abstract]
5. Shaw GM, Carmichael SL, Laurent C, et al; Maternal nutrient intakes and risk of orofacial clefts. Epidemiology. 2006 May;17(3):285-91. [abstract]
6. Czeizel AE, Timar L, Sarkozi A; Dose-dependent effect of folic acid on the prevention of orofacial clefts. Pediatrics. 1999 Dec;104(6):e66. [abstract]
7. Zucchero TM, Cooper ME, Maher BS, et al; Interferon regulatory factor 6 (IRF6) gene variants and the risk of isolated cleft lip or palate. N Engl J Med. 2004 Aug 19;351(8):769-80. [abstract]
8. Carinci F, Scapoli L, Palmieri A, et al; Human genetic factors in nonsyndromic cleft lip and palate: An update. Int J Pediatr Otorhinolaryngol. 2007 Jun 30;. [abstract]
9. Merritt L; Part 1. Understanding the embryology and genetics of cleft lip and palate. Adv Neonatal Care. 2005 Apr;5(2):64-71. [abstract]
10. OMIM; Apert's Syndrome
11. OMIM; Hemifacial microsomia
12. OMIM; CHARGE Syndrome
13. Willatt L, Cox J, Barber J, et al; 3q29 microdeletion syndrome: clinical and molecular characterization of a new syndrome. Am J Hum Genet. 2005 Jul;77(1):154-60. Epub 2005 May 25. [abstract]
14. OMIM; van Der Woude syndrome
15. Merritt L; Part 2. Physical assessment of the infant with cleft lip and/or palate. Adv Neonatal Care. 2005 Jun;5(3):125-34. [abstract]
16. Bille C, Winther JF, Bautz A, et al; Cancer risk in persons with oral cleft--a population-based study of 8,093 cases. Am J Epidemiol. 2005 Jun 1;161(11):1047-55. [abstract]
17. Hunt O, Burden D, Hepper P, et al; The psychosocial effects of cleft lip and palate: a systematic review. Eur J Orthod. 2005 Jun;27(3):274-85. [abstract]
18. Papadopulos NA, Papadopoulos MA, Kovacs L, et al; Foetal surgery and cleft lip and palate: current status and new perspectives. Br J Plast Surg. 2005 Jul;58(5):593-607. [abstract]

Internet and further reading

• OMIM; Orofacial Cleft 1; OFC1
• Tolarova MM, HeeSoo Oh; Cleft Lip and Palate, eMedicine, Mar 2009.
• CLAPA; The Cleft Lip and Palate Association

Acknowledgements