Cleft Lip & Palate

Eduardo D. Rosas Blum, MD August 7, 2007

While on call

25yo G1 P1 delivers a full-term infant after 12hrs of uneventful labor. The infant was found to have a cleft lip and palate. How should the care for this infant, and his mother, be?

Birth defects

Malformations

alterations in normal development abnormal mechanical force on an otherwise normal fetus disruption of an otherwise normal developmental process

Deformations

Disruptions

Introduction

Most common craniofacial malformation Cleft lip with or without cleft palate (CL/P) or isolated cleft palate (CP). CL/P and CP differ with respect to

Embryology, etiology, candidate genes, associated abnormalities, and recurrence risk.

Unilateral incomplete

Unilateral complete

Bilateral complete

Incomplete cleft palate

Unilateral complete lip and palate

Bilateral complete

Prevalence

CL/P is more common than CP and varies by ethnicity. CL/P

High in American Indians and Asians (1/500 newborns) Low in American blacks (1/2000 newborns) Intermediate level in Caucasians (1/1000 newborns)

Isolated CP occurs in only 1/2500 newborns and does not display

Cleft Lip

Complete closure at 35 days postconception:

7 weeks from the LMP. Lateral nasal, median nasal, and maxillary mesodermal processes merge.

Failure of closure can produce unilateral, bilateral, or median lip clefting. Left side unilateral cleft is the most common.

Cleft lip Severity

Mild, involving only the lip Extend into the palate and midface thereby affecting the nose, forehead, eyes, and brain.

Cleft Palate

Lack of fusion of the palatal shelves. Abnormalities in programmed cell death may contribute to lack of palatal fusion(?). Isolated disruption of palate shelves can occur after closure of the lip Palatal closure is not completed until 9 weeks post-conception.

Etiology

Genes Control cell patterning, cell proliferation, extracellular communication, and differentiation Clefting usually represents a genetically complex event Single Mendelian disorders associated with clefting are rare 2 to 20 genes are thought to interact to result in facial clefting

Etiology

Dlx gene

Direct the destination of the distal skeletogenic mesenchyme elements to the palate. Mutations of these genes result in isolated palatal defects. Protein that mediates ectodermal functions, might regulate the outgrowth and fusion of the facial domains. Receptor ligand, usually a rare variant of TGFalpha Family histories of cleft defects

Sonic hedgehog gene

TGF-alpha variant

Etiology

TGF-beta-3 gene
Expressed just prior to palatal fusion. Results in isolated cleft palate.

IRF 6

Identified in autosomal dominant van der Woude syndrome.

Several agents that are associated with an increased frequency of midfacial malformation. Medications phenytoin, sodium valproate, methotrexate. With corticosteroids there is no evidence of an increase in malformations.

Environmental agents

Possible association could not be excluded

Etiology

Cigarette smoking

Noted with mothers of children with facial clefting, both CL/P and CP. Teratogenesis has been attributed to hypoxia as well as a component of tobacco (cadmium). Associated with an increased risk of fetal facial clefting. Alterations in cell membrane fluidity or reduced activity of specific enzymes such as superoxide dismutase. Contributes to a range of birth defects. Evidence is emerging for a similar association with the development of CL/P.

Alcohol

Folate deficiency

Prenatal Diagnosis

Diagnosed until the soft tissues of the fetal face can be clearly visualized sonographically (13 to 14 weeks). The majority of infants with cleft lip also have palatal involvement:
85% of bilateral cleft lips 70% associated with cleft palate. Cleft palate with an intact lip comprises 27% of isolated CL/P

Prenatal Diagnosis

The sensitivity is highest when is associated with other structural anomalies. Isolated CL/P in a low risk population, the sensitivity may only reach 50 percent. Cleft palate with an intact lip is the most difficult orofacial malformation to diagnose prenatally. Detected in only 13 of 198 cases in one large series. Three-dimensional ultrasound, can provide

Prenatal Diagnosis

Syndrome ?

A thorough examination of the newborn or stillbirth is always warranted. Orofacial clefting is noted in over 300 syndromes. 3 deserve additional comment.

frequency, variable presentations, and modes of inheritance

Deletion of chromosome 22q11

DeGeorge syndrome. Spectrum in addition to cleft palate:

Conotruncal cardiac defects, thymic hypoplasia, and velopharyngeal webs.

Majority of cases represent a new microdeletion In families with conotruncal malformations and/or CP, further evaluation is appropriate.

Oral-facial-digital syndrome, type I

X-linked dominant syndromes. Manifestations in affected females are variable and subtle:
hyperplastic frenula cleft tongue cleft lip/palate digital anomalies

Autosomal dominant disorder Downward slanting palpebral fissures, micrognathia, dysplastic ears, and deafness.

Treacher-Collins syndrome

Mental development is normal.

The mutations appear to increase cell death in the prefusion neural folds. A family history with deafness, ear abnormalities, or CP.

Amniocentesis for karyotype should be offered.

Obstetrical Management

high rate of chromosomal defects

Difficulty in prenatal sonographic diagnosis supports chromosomal evaluation As of January 2002, "in utero" correction had been attempted only once in Mexico

The child delivered prematurely and

Recurrent Risk
Affected relative Parent Sibling Parent and Sibling Two Siblings Cleft palate only Parent Sibling Parent and sibling 7% 2 5% 14 17% Risk in child, percent 2% 4 7% 11 14% 10% Cleft lip with or without cleft palate

The Care will entail attention, not only to surgical repair, but also more immediate needs such as feeding. Primary lip repairs can often be undertaken at three months of age with palatal repairs around six months. Additional surgeries as well as speech and orthodontic therapies are often needed. The cleft Lip and Palate Association ( www.clapa.com/) provides support and information for parents.

Postnatal Management

Cleft lip repair. The edges of the cleft between the lip and nose are cut (A and B). The bottom of the nostril is formed with suture (C). The upper part of the lip tissue is closed (D), and the stitches are extended down to close the opening entirely (E).

Feedings

Infants with CL/P have few feeding problems. If the cleft involves the hard palate, the infant is usually not able to suck efficiently.

Experiment (special nipples or alternate feeding positions)

The infant should be held in a nearly sitting position during feeding

Prevents flowing to the back into the

Feedings

It is important to keep the cleft clean Breastfeeding is extremely challenging.

Haberman Feeder

Activated by tongue and gum pressure. Milk cannot flow back. Replenished continuously as the baby feeds. Prevents the baby from being overwhelmed with milk. A gentle pumping action to the body of the nipple will

Family Care

Have a family meeting with both parents present. Infant should be brought to the parents as soon the mother and the infant are in satisfactory condition. Allow the parents to observe, react and ask questions about the infant. Explained the defect and the how the surgeon will most likely correct the clefts. Before and after pictures are helpful.

Family Care

Emphasize as possible to the parents the normal healthy features of the baby. The baby should be present when the defect is explained, as ugly as the cleft might be. Training the mother about feeding techniques and avoiding complications.

Tom Brokaw

American television journalist.

Jesse Jackson

Politician, professional civil rights activist and Baptist minister

Peyton Manning Annie Lennox

NFL quarterback Scottish pop musician and vocalist

Mark Hamill Tutankhamun

Actor Egyptian Pharaoh who may have had a cleft lip according to diagnostic imaging

References

Klaus & Fanaroff. Care of the high-risk neonate. Saunders. 5th edition. 2001 USA. Colin D. Rudolph Rudolphs Pediatrics McGrawHill. 21st edition. 2002. USA. Christensen, K, et al. Cleft-twin sets in Finland 1948-1987. Cleft Palate Craniofac J 1996; 33:530. Clementi, M, et al. Evaluation of prenatal diagnosis of cleft lip with or without cleft palate and cleft palate by ultrasound: experience from 20 European registries. EUROSCAN study group. Prenat Diagn 2000; 20:870. Milerad, J, et al. Associated malformations in infants with cleft lip and palate: a prospective, population-based study. Pediatrics 1997; 100:180. Cockell, A, Lees, M. Prenatal diagnosis and