Genetics research benefits children

synapse: University of Nevada, Reno School of Medicine

Colleen Morris, M.D., has devoted her life to pediatric genetics research.

Story by Anne McMillin, APR

The professor of pediatrics and chief of pediatric genetics research at the School of Medicine focuses on the study and treatment of pediatric genetic disease, in particular the etiology and genotype-phenotype correlation of Williams syndrome. In addition, she works to identify and find treatments for children with fetal alcohol syndrome and holds genetics clinics to diagnose children’s illnesses for the Clark County School district and the Lili Claire Foundation, a charitable organization dedicated to helping children with neurogenetic diseases.

"Genetics is a fascinating field—nothing stays the same and consequently, I am never bored," said Morris, who has been with the School of Medicine since 1988 and practices in Las Vegas. She said the field has come a long way in the last 25 years from banding techniques for chromosome identification to the latest microarray technology that allows detection of single gene copy number variation.

Williams syndrome

Morris first became involved in the research aspect of Williams syndrome in the mid-1980s, when she completed a study of the natural history of the condition.

In 1993, Morris was part of the team that discovered that Williams syndrome results from deletion on one of the number 7 chromosomes that includes the elastin gene.

This deletion causes multisystem manifestations including elastin arteriopathy (arterial stenosis), intellectual disability, behavior problems and connective tissue problems.

"There are 26 to 28 genes on chromosome 7 that are deleted in Williams syndrome," said Morris, who has been working to determine what genes deleted in the region account for each particular physical or mental manifestation.

Her research team discovered that the deletion of the elastin gene results in the vascular disease that causes the most significant morbidity and mortality in Williams syndrome. They determined that another missing gene in the region, GTF2I, is associated with cognitive disability.

Currently, Morris focuses her attention on finding the missing gene that leads to anxiety in Williams syndrome children. Once the gene that causes anxiety is identified, she said it can lead to more tailored treatment in the general population.

Working with the University of Nevada, Las Vegas biology department and its genetics core lab, Morris is able to use microarray technology to identify which genes are deleted or rearranged.

"We are sharing equipment and resources to advance research at both our institutions," she said. Morris and her team are able to look at the variation in each pair of chromosomes from a patient's mother and father, leading to new discoveries of genetic factors that influence Williams syndrome.

"Some individuals have very severe cardiovascular disease while others have only mild symptoms. We are trying to determine what genetic factors underlie the variability in order to find new ways to treat the manifestations of the condition. Discoveries regarding the underpinnings of arterial disease in Williams syndrome may have applicability to the treatment of arterial disease in the general population," said Morris.

While deletion of a portion of chromosome 7 leads to Williams syndrome, its duplication leads to a new syndrome called duplication of the Williams syndrome region, or "dup 7." The differences in children with these two related conditions are polar opposites: children with Williams syndrome are good with language abilities, but have poor fine motor skills while those with "dup 7" syndrome have good fine motor skills but poor speech and language skills.

Fetal alcohol syndrome

For her work in the realm of public health, Morris gravitated to the issue of fetal alcohol syndrome which is caused by alcohol consumption during pregnancy.

"One percent of births in Nevada have fetal alcohol syndrome spectrum disorders," said Morris, adding there is no safe amount of alcohol use during pregnancy.

"Alcohol exposure at any time during pregnancy affects the brain, which continues to develop throughout the pregnancy."

Part of the problem is educating women regarding the use of alcohol when pregnant. Nearly 50 percent of patients Morris sees have unplanned pregnancies and consume alcohol before they realize they are pregnant. In teenage mothers, binge drinking is more prevalent and these future mothers may not know they are pregnant until as late as the second trimester.

Children with fetal alcohol syndrome have learning and behavior problems on the mild end of the spectrum, to severe neurological problems, small head size, birth defects and mental retardation on the severe end.

Early diagnosis, before age six, can lead to appropriate treatment resulting in a more successful outcome. If not diagnosed and treated early, fetal alcohol syndrome can result in more severe secondary disabilities later in life that are more costly to treat.

Since 2005, Morris has partnered with the Lili Claire Foundation and the Nevada State Division of Health to conduct fetal alcohol syndrome diagnostic clinics using a multidisciplinary approach to identify, diagnose and offer treatment alternatives.

Pediatric psychiatrists, pediatric neuropsychologists, genetic counselors and social workers combine their expertise to diagnose a child and recommend a treatment plan to parents. Johanna Fricke, M.D., a School of Medicine developmental behavioral pediatrician, helped design the clinics, which now include clinical faculty members Dr. Julie Beasley, neuropsychologist, and Dr. Joseph Kithas, pediatric psychiatrist.

In 2008 and 2009, Morris furthered her work on fetal alcohol syndrome through the Lili Claire Foundation with a project to provide social skills groups for children with this condition and parenting classes for their adoptive or foster parents.

Fetal alcohol syndrome children are often put up for adoption or placed in foster care due to their birth parents' circumstances. Through the Lili Claire Foundation groups, Morris, who serves as the foundation's medical director, and her team provide evaluations, genetic counseling and consultation for individuals with neurogenetic disorders. The goal is to determine if a child has fetal alcohol syndrome and then help determine the most appropriate treatment in terms of medicine and education for improving the quality of life.

Genetic clinics

When children in the Clark County School District are identified as having a learning problem a genetic cause is often suspected. The educator in the classroom may refer a child to the school nurse who contacts the family and asks if they want to enroll their child in a genetic diagnostic clinic.

"This is a true team effort because that child wouldn't necessarily make it to a genetics clinic if not through referral from the educational system," Morris said.

The goal of the genetics evaluation is to provide accurate diagnoses and information for families regarding genetics disorders or birth defects. Counseling helps individuals understand the causes of various abnormalities and the medical tests available to detect their presence. Geneticists provide information regarding treatment and research for rare genetic disorders. Knowing the strengths and weaknesses typically associated with a syndrome, school personnel then craft the most appropriate individual educational plan for the student.

At each of the 10 school district genetics clinics held during an academic year, family history, pregnancy history and medical and educational records are reviewed, and the child undergoes a physical exam. In some cases, a diagnosis can be made the same day; sometimes, further genetic tests are recommended.

A follow-up session may be scheduled with the family to discuss the diagnosis of a particular syndrome, expectations the family should have for their child's behavior and treatment options to determine an educational plan to address the best way for the child to learn considering his or her limitations. Referrals are made to appropriate community, medical and education services as needed.

"We work with the family and their insurance and, often with Dr. Morris' help, offer resources to the parents," said Sally Jost, R.N., director of related services at the school district, who oversees the genetic clinics at the district and works with Morris.

"If the classroom behavior can be attributed to a genetic syndrome, we have different educational profiles that Dr. Morris helps us identify. From there, we can take the best approaches to respond to that child's educational abilities and needs," Jost said.

Morris also conducts general genetics clinics in partnership with the Lili Claire Foundation to determine cases of genetic disorders and birth defects.

Nicole Cannon, program coordinator for the Lili Claire Family Resource Center in Las Vegas, said the genetics clinics put on jointly by the foundation and the medical school are one of the only places in southern Nevada still doing clinics in light of state budget cuts.

Lili Claire Foundation clinics are held once or twice per month with five to eight children assessed each time and follow essentially the same multidisciplinary process as the school district.

"Early intervention is the key and we can offer the services needed so these children's lives are better," Cannon said. "We are grateful to have Dr. Morris and to be working with the Lili Claire Foundation to help our children."