By Kristina Kahl | Genomic Services, Advanced Diagnostics

July 10, 2018 Insights

Cleft lip and cleft palate are two of the most common problems found in newborns, and July is Cleft and Craniofacial Awareness Month. A cleft lip is an opening in the lip, while a cleft palate is an opening in the roof of the mouth. During the beginning weeks of pregnancy, a baby’s palate and lip are normally “open”, and then come together during the first trimester. Sometimes this process doesn’t occur properly, and the lip or palate may not close completely.

In the U.S., approximately 1 in every 600 babies is born with a cleft lip and/or cleft palate and most are considered “multifactorial,” meaning they are caused by a complex combination of genetic and non-genetic factors.  In the majority of cases, a baby’s cleft is isolated.  This means the baby does not have any other health problems besides the cleft; however, in some cases the cleft is part of a genetic syndrome and associated with other health problems. There are more than 300 genetic syndromes associated with cleft lip and/or palate. One such syndrome is 22q11.2 deletion syndrome, also known as DiGeorge or velocardiofacial syndrome. Approximately 1 in 2000-4000 individuals is born with this syndrome, and some experts believe the incidence may be higher due to its wide variability of features and severity.

Individuals with 22q11.2 deletion syndrome are missing approximately three million base pairs (building blocks) of DNA on one copy of chromosome 22, a region containing approximately 40 genes.  While 90%-95% of cases occur in families with no family history of this disorder, the remainder of cases are inherited from a parent, who may not even realize he or she is affected. For someone with 22q11.2 deletion syndrome, each time he or she has a child, there is a 50% chance the child will inherit the deletion.

As mentioned above, 22q11.2 deletion syndrome is quite variable, even among members of the same family. Besides cleft palate, additional findings associated with the syndrome can include congenital heart defects, learning difficulties, immune deficiencies, low serum calcium levels, thyroid disorders, swallowing and gastrointestinal problems, kidney problems, hearing loss, eye problems, and psychiatric illness.

Early diagnosis and treatment can improve health outcomes and prevent complications. For example, calcium supplementation and monitoring by an endocrinologist can prevent low calcium-related seizures, and detailed cardiac evaluations can be performed in order to identify and treat congenital heart disease.   Patient-specific feeding strategies for palate and gastrointestinal abnormalities can ensure proper nutrition, and close monitoring of the immune system is important when dealing with infections and planning for vaccinations. Every baby born with a cleft palate, with or without a cleft lip, does not necessarily have 22q11.2 deletion syndrome, but awareness is key to early testing and intervention.

Most cases of 22q11.2 deletion syndrome can be diagnosed in the laboratory through specific cytogenetic or molecular genetic testing.  These tests can be performed on a blood sample, or if the syndrome is suspected prenatally, via amniocentesis or chorionic villus sampling (CVS). Prenatal screening for the 22q11.2 deletion is now available by cell-free DNA screening, also known as noninvasive prenatal screening. If cell-free DNA screening is positive, prenatal diagnosis by amniocentesis or CVS would be necessary to confirm or rule out the presence of the deletion. For more information on testing for 22q11.2 deletion syndrome at Quest Diagnostics, contact Quest Genomics Client Services, at 866.GENE.INFO (866.436.3463).

For more information on cleft lip, cleft palate, and other craniofacial differences, visit the American Cleft Palate-Craniofacial Association website at http://www.cleftline.org. For more information on 22q11.2 deletion syndrome, visit The International 22q11.2 Foundation, Inc. website at http://www.22q.org/.