Causes Of Birth Defects: Cleft Lip/Palate

The causes of birth defects are various. A cleft lip or cleft palate, also known as Craniofacial-Oral-Dental birth defects, can be caused by Accutane or by other factors. A Weitz & Luxenberg attorney can help you and your family if your child is suffering from a Craniofacial, Oral, or Dental birth defects. You may fill out this simple form and get your free case review today.

Every hour and 15 minutes throughout the United States, a child is born with cleft lip, with or without cleft palate. Nearly two infants in every 1,000 live births have some type of craniofacial birth defect. Each of these children requires multiple surgical procedures--often four operations within the first two years of life--and a coordinated team of health care professionals to address the challenges presented by the most common of human birth defects.

Over the next 10 to 15 years, such a child may require the care available through pediatrics, genetics, anethesiology, neurosurgery, oral-maxillofacial surgery, plastic surgery, otolaryngology, pedodontics, orthodontics, prosthodontics, speech therapy, nursing, social and psychological services--and the unconditional support and participation of the family.

There are 4.2 million births in America every year, and more than 51 million children are enrolled in kindergarten through 12th grade. With craniofacial-oral-dental birth defects having a prevalence of 1.77 per 1,000 live births, this means that the health costs approach $1 billion each year to provide the comprehensive and time-consuming habilitation required to enable each child born with such birth defects the opportunity to pursue a productive life.

Beyond these sobering statistics is an emerging new approach toward a molecular understanding of these '"experiments- ments of nature." What's in a face? What are the basic rules for forming the human face and how are these principles altered to produce human craniofacial dysmorphogenesis?

A number of congenital craniofacial-oral-dental birth defects can be prevented by reducing established risk factors associated with human craniofacial malformations.

For example, isotretinoin (Accutane, Roche Laboratories), a retinoic acid analogue, is an extremely effective therapeutic agent for the treatment of cystic acne. Yet when administered during the first trimester of pregnancy, this vitamin A analogue can produce severe craniofacial and oral clefts and limb defects.

Alcohol is a well-established risk factor that can cause fetal alcohol syndrome with associated craniofacial-oral-dental birth defects.

Anticonvulsant medications such as phenytoin (Dilantin, Parke-Davis) and various other environmental insults or teratogens also can produce severe human birth defects involving the face, jaws and teeth. Pregnant women who smoke increase the risk of cleft lip, with or without cleft palate. If these teratogens were eliminated before conception and during pregnancy, many thousands of craniofacial-oral-dental birth defects could be prevented every year, resulting in significant human benefits and cost savings.

Smoking as a major risk factor for cleft lip, with or without cleft palate, presents a very compelling argument for dentists to educate, motivate and counsel the prospective pregnant women within our sphere of influence: dental patients; dental office, clinic, laboratory or hospital staff members; faculty, students and administrative support staff at our nearby academic health science center; immediate and extended family members; and our friends and business associates.

With nearly 60 percent of Americans visiting their dentist every year, we dentists are clinically positioned to serve as advocates for health promotion and disease prevention.

A recent study by the California Birth Defects Monitoring Program reported that mothers who smoked 20 or more cigarettes per day during the month before conception through the first three months of pregnancy were more than twice as likely to have infants with cleft lip and/or cleft palate. Those mothers who smoked less were about 1.5 times as likely to have infants with oral clefts.

The mother's age, race or ethnicity and education did not significantly alter the effects of smoking. Moreover, the use of multivitamins did not mitigate the risk of oral clefting associated with smoking. As yet, we do not know how smoking produces oral clefting. Presumably, carbon monoxide and nicotine--agents released through smoking--lower the oxygen available to the embryo during critical stages of craniofacial-oral-dental development.

Even our limited knowledge of this process, however, points to the need for the dental profession to be involved in urging the elimination of tobacco use during pregnancy.

The craniofacial structures develop from five discrete primordia, which fuse to form the distinctive bilateral symmetry of the human face, jaws and teeth, including the frontonasal prominence covering the forebrain and the paired maxillary and mandibular prominences. These prominences are regions of mesenchymal cell growth. These mesenchymal cells provide the cell lineages that become different phenotypes, such as cartilage, bone, dental pulp, dentin, cementum and periodontal ligament.

What's more, these mesenchymal cell lineages derive from hindbrain neuroectoderm-derived cranial neural crest cells during the third week of pregnancy. The timing, cell migration pathways and patterns of gene expression within each of these five facial primordia continue through the eighth week of gestation when the human face is readily identifiable.

Human face and jaw development reflects both the biomechanical influences of underlying structures (such as the forming brain and the sensory organs--sight, smell, taste, touch and hearing). Genes that control the brain and associated sensory organ appendages also regulate craniofacial-oral-dental formation and limb, heart and lung development.

The National Institute of Dental Research and many of the other institutes, centers and offices that compose the National Institutes of Health have invested and continue to invest in basic, translational, applied and patient-oriented research that can promote health, reduce disease, and develop and refine improved diagnostics, therapeutics and biomaterials.

At this time, we do not know the specific causes of most craniofacial-oral-dental birth defects. Available data suggest that almost 20 percent of these tragic birth defects are either genetic or familial. The vast majority, however, are caused either by defined risk factors (excess vitamin A analogue, anticonvulsant medications such as phenytoin, alcohol use and smoking cigarettes) or unknown causes.

While fundamental research pursues the molecular genetics of developmental biology, we can reduce the disease burden of craniofacial and oral clefts by better informing the health professions and the public about known risk factors and their role in birth defects.

Hal Slavkin, DDS, NIDCR Director 1995 - 2000
(JADA. May 1996; 127(5):681-2)

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