The Quarterly Consult is a quarterly supplement to the Bulletin highlighting pediatric clinical expertise. If you have an item of interest to include in the Quarterly Consult, contact Dr. Steve Dassel at 206-625-7373, mailbox 8588.
By Steve Dassel, MD
I spoke with Michael Cunningham, MD, PhD, medical director of the Seattle Children's Craniofacial Center at Children's Hospital about cleft lip and palate. Michael is also chief of the Division of Craniofacial Medicine at the University of Washington (UW), Department of Pediatrics, and is an associate professor of pediatrics at UW.
Q: Michael, please give us a little background about clefts and their racial, ethnic and gender incidences.
A: Northwest Native Americans and Asians have the highest reported incidence at approximately 1 in 250 to 350 live births. Caucasians have an estimated incidence of 1 in 700 to 1,000 live births, and in African Americans, the incidence is 1 in 3,000 to 6,000 live births. However, recent data from studies in sub-Saharan Africa suggest that the incidence in these populations may be much higher than previously thought. Cleft lip and palate is more common in males and isolated cleft palate is more common in females.
Q: Are there geographic pockets of higher incidence?
A: To my knowledge, all variation in incidence is thought to reflect racial rather than geographical differences. Interestingly, about three years ago, we noted a dramatic decrease in the number of clefts being referred to us, dropping from 120 a year to only 60 a year. We couldn't explain this by any change in referral patterns, and this reduction in the number of patients was also seen at other centers in the United States and abroad. It has now, just as inexplicably, returned to previous levels.
Q: Is it more common for a child to have cleft lip and palate or an isolated cleft lip or cleft palate?
A: Cleft lip and palate (CLP) is about twice as common as cleft palate, which has about the same incidence as cleft lip. Cleft palate only (CPO) has the highest association with syndromes.
Q: Such as?
A: Stickler syndrome is an example. It is caused by a collagen gene mutation that has ophthalmic, orthopedic and cleft implications.
Q: What's the ophthalmology picture?
A: Early myopia and a higher risk of retinal detachment and glaucoma. On physical examination the eyes can appear prominent, so look for this sign when examining a child with CPO. This feature is often missed due to the endearing appearance of these infants; they are quite cute.
Q: And the orthopedic problem?
A: Early degenerative arthritis.
Q: How common is Stickler syndrome in patients with CPO?
A: Although there are no figures for the frequency of Stickler syndrome in children with CPO, it is estimated that between 10% to 20% of children with Robin malformation have Stickler syndrome. Robin malformation is defined by a classic triad of micrognathia, U-shaped posterior cleft palate, and glossoptosis. Glossoptosis literally means "falling tongue" and refers to the posterior placement of the tongue leading to airway obstruction.
Q: Any other syndromes?
A: Also associated with CPO is a deletion on chromosome 22 (22q11.2). This condition is known by several names, including velocardiofacial syndrome (VCFS), DiGeorge syndrome, CATCH 22, and Shprintzen syndrome. Previously, VCFS and DiGeorge and Shprintzen syndrome were thought to represent distinct syndromes; we now know that this common deletion on chromosome 22 leads to all of these conditions with highly variable phenotypes, including cleft palate, tetralogy of Fallot, and psychosis.
Q: So, CPO is far more significant than cleft lip and palate?
A: In the absence of a syndrome or Robin malformation, CPO is no more serious than CLP. But those children born with Robin malformation have a high frequency of airway compromise and associated syndromes. That said, I agree, we need to be much more vigilant with the evaluation of a child with CPO than a child with CLP.
Q: Let's turn to etiologies and, therefore, perhaps prevention.
A: Research focusing on the potential role of vitamin supplementation in the prevention of open neural tube defects demonstrated a reduction in clefting in the infants of mothers taking supplemental folic acid. As little as 400 mcg of supplemental folate has been shown to reduce the risk of having a child with a cleft. Most prenatal vitamins have 800 mcg of folic acid, but they must be taken before conception to have a protective effect. Most women begin prenatal vitamins between four to six weeks of gestation, and lip closure is completed in the fifth week of gestation.
Q: What are your thoughts on etiology?
A: There is no doubt that genetics plays a role in the etiology of clefting. It has been estimated that more than 30% of children with clefts have a relative with a cleft. If a Caucasian couple's first child has a cleft, the risk that their next child will have a cleft is about 3% to 4% (increased from a baseline risk of about 0.1%). A parent with a cleft has about a 10% chance of having a child with a cleft. As you can see, these recurrence rates do not fall into typical patterns of Mendelian inheritance. It has been suggested that a combination of several genes predispose a couple to having a child with a cleft, and there is strong evidence for environmental effects such as alcohol consumption, smoking, and diet, specifically folate intake.
Q: What about treatment - especially its timing?
A: In our center, most children with bilateral and severe unilateral clefts are treated with a procedure known as nasoalveolar molding. This is started at about 2 weeks of age. It is best described as presurgical orthodontics performed on an infant. This is managed by our orthodontists and surgeons and gets the alveolus in good position, so there is less traction on the lip, which is repaired at 3 to 4 months.
Q: Why wait?
A: We could repair a cleft lip at 2 weeks of age with an excellent surgical result. We wait to reduce anesthesia risks. The goal is the best possible long-term outcome with the fewest number of surgeries and the least risk to the child.
Q: What about timing for the palate repair?
A: The palate is repaired at 9 to 12 months. The timing is driven by language development, which takes off at about 12 months. Palate repair earlier than 9 months of age is thought to negatively impact midfacial growth, and repair after 14 to 16 months of age has a negative impact on language development. Finally, alveolar ridge bone grafting is performed at 8 to 9 years of age. With our current approach, a bone graft is taken from the hip to repair the boney defect in the maxilla. The timing of this procedure is based on tooth eruption in the region of the cleft in order to preserve natural dentition and prevent the necessity of dental implants in the future. Some children with CLP have significant problems with midfacial development necessitating jaw surgery when they have completed growth. As you can see, CLP is not a problem of infancy; many children have surgeries until they are 16 to 18 years of age.
Q: How is feeding managed? Can the CLP infant be breast-fed?
A: No. Children with cleft palate, whether isolated or as part of CLP, are unable to generate sufficient negative pressure necessary for suckling breast or bottle. We encourage the use of breast milk but with the use of specialized bottles.
Q: Such as?
A: There are a variety of squeeze bottles and specialized nipples, like Pigeon nipple and Haberman Feeder, that are designed to allow an infant who cannot generate negative pressure to feed. Squeeze bottles are just what they sound like - bottles that a parent squeezes to express milk into their infant's mouth. The Pigeon nipple has a one-way valve, and a thinner, more supple side of the nipple, so that tongue and jaw action can express milk into the infant's mouth. The Haberman Feeder is basically a combination of these two methods (squeeze and one-way valves). Every infant and family has a preferred method of feeding, so there is value to having a variety of systems to choose from.
Q: What about airway problems in CLP patients?
A: CLP patients usually do not have airway problems. However, CPO patients have a high frequency of airway obstruction because there is an increased frequency of glossoptosis. Airway obstruction is most commonly seen in children with Robin malformation (micrognathia, cleft palate, glossoptosis). Jaw size is, therefore, crucial and the initial treatment is prone positioning. Many children with Robin need more aggressive treatment, including the use of nasopharyngeal airways and, in severe cases, tracheostomy.
Q: In closing, what mistakes do you see in our referrals of cleft patients?
A: There is not much of a problem in this regard. Occasionally we see a feeding problem not referred soon enough, and failure to thrive complicates the management of a child with a cleft. We like to see patients with clefts by 2 weeks of age. Again, infants with cleft palates cannot breast-feed, and families need to be trained how to feed their infants for optimal growth, so we are happy to evaluate them at any time after birth if there are feeding concerns. These children have at least two surgeries in the first year of life; nutritional health is an important part of surgical outcome.
Q: Anything else?
A: Occasionally a cleft palate is missed. Every textbook I have seen instructs pediatric providers to examine the palate of a newborn by palpation. I would strongly encourage providers to examine the palate visually using a tongue blade to depress the tongue. A quick peek at the palate will document its integrity with far more accuracy than palpation. The tiniest of posterior palatal clefts can have a profound effect on suckling and, hence, weight gain. So look, don't just feel.
We also have an active prenatal counseling program in place and meet about 50% of our families before their child is born. Feel free to refer interested families for this service, where we discuss issues of management, feeding and the psychosocial impact of the diagnosis.
Q: We are usually warned ahead of time about an obvious congenital defect in the newborn by the newborn nursery nurses. Can we call the Craniofacial Center before we make that first trip to the hospital after delivery and speak with the newborn's parents?
A: Certainly. I suspect families will feel much more comfortable if you can lay out a plan for the approach to this problem right away. Children's Craniofacial Center has a craniofacial pediatrician on call 24/7 to answer any questions you may have. Call 206-987-7777 and ask for the craniofacial pediatrician on call. For less urgent calls, feel free to call our craniofacial nurse specialists at 206-987-1117 during work hours. Our web page has extensive information about our treatment of children with CLP.