What Are the Genetics of Cleft Lip and Palate?

Patient Presentation
A 5-day-old female came to the inpatient floor for continued monitoring of her feeding.
The past medical history showed a 38 week female who had been diagnosed by intrauterine ultrasound to have a cleft lip and palate.
This was confirmed at birth.
The family history was positive for thyroiditis and cancer. It was negative for congenital abnormalities, genetic syndromes, neurological or learning problems.
The pertinent physical exam showed an alert, interactive infant who was 4% decreased from birth weight with the rest of her vital signs being normal.
HEENT revealed a left sided cleft lip, bilateral cleft palate (complete on the left and incomplete on the right). Nares were patent.
She had a small sacral dimple within the gluteal cleft that the base could easily be seen. The rest of her examination was normal.
The diagnosis of bilateral cleft palate and unilateral cleft lip was reconfirmed. She was evaluated by the local cleft lip and palate multispecialty team.
The patient’s clinical course over the next days found her parents to be mastering proper positioning and use of a special squeeze bottle with a premature infant nipple using regular infant formula.
She was discharged home and continued to gain appropriate weight. At 4 months of age, she underwent a successful operative procedure to close the cleft lip and to placed bilateral pressure equalizing tubes in her ears.
She had two episodes of otitis media over the next 8 months when she returned for closure of the bilateral cleft palate which was successful.
Three months later her family moved to another region of the country and care was transferred to a new multispecialty team.

Patients with clefting often need the services of a multispecialty team of providers. Each child is unique and may need some or more specialists including
speech and audiology, nutrition, surgery (otolaryngology, plastic, dental/orthodontics), psychiatry/psychology, social work, and genetics.

Problems associated with cleft lip and palate include:

  • Dental and orthodontia problems
  • Feeding difficulties
  • Hearing loss – most commonly conductive
  • Language disorders – expressive and receptive language
  • Speech disorders – articulation, phonation and resonation disorders commonly caused by velopharyngeal insufficiency
  • Obstructive sleep apnea
  • Psychosocial problems
  • Surgical challenges to repair
  • Surgical complications
  • Treatment for other problems associated with genetic syndromes

Weight gain can be one of the most vexing problems for families. However, usually with the help of nutritionists, babies with clefts can successfully grow.
Many babies can successfully breastfeed or bottle feed. However, others require special feeding bottles such as the Special Needs Feeder®, Cleft Lip and Palate Nurser® or Pigeon Bottle®.
Other children may need oral gastric feedings too for nutritional maintenance and growth.
Babies usually need to be around 10 pounds of weight and 3 months of age before the first surgical repair.

Learning Point
Clefting occurs ~ in 1/300 Native Americans, 1/500 in Asian and 1/800 Caucasian children in the United States.
Most cases of cleft lip and palate are genetically isolated cases (75%) but some are associated with specific genetic anomalies (25%).
In isolated cases, there is only ~4% recurrence risk in future siblings.

Van der Woude syndrome (associated with lip pits), Stickler syndrome (associated with Pierre Robin sequence) and 22q11.2 deletion syndrome (also known as velo-cardio-facial syndrome) are the most common syndromes associated with clefting.
Other syndromes include CHARGE syndrome, Kabuki syndrome, Oculo-auriculo-vertebral dysplasia, Opitz syndrome,
Oral-facial-digital syndrome, Popliteal Pterygium syndrome and Wolf-Hirschhorn syndrome.

Cleft lip and palate occurs in 46% of patients, isolated cleft palate occurs in 32% of patients, and isolated cleft lip occurs in 21% of patients.
Unilateral left lip is more common than bilateral cleft lip which is also more common than unilateral right cleft lip.

Questions for Further Discussion
1. What specialists are on your local cleft lip and palate multidisciplinary team?
2. How often is cleft lip and/or palate found on prenatal ultrasonography?
3. Why are pressure-equalizing ear tubes often placed with the first surgery?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Cleft Lip and Palate and Facial Injuries and Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

Kasten EF, Schmidt SP, Zickler CF, et.al.
Team care of the patient with cleft lip and palate.
Curr Probl Pediatr Adolesc Health Care. 2008 May-Jun;38(5):138-58.

Online Mendelian Inheritance in Man. Cleft Palate, Isolated. Available from the Internet at http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=119540 (rev. 9/6/07, cited 10/6/08).

Online Mendelian Inheritance in Man. Orofacial Cleft 1.
Available from the Internet at http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=119530 (rev. 7/17/08, cited 10/6/08).

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.

    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement

    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Interpersonal and Communication Skills
    17. A therapeutic and ethically sound relationship with patients is created and sustained.

    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Systems Based Practice
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

    November 17, 2008