Researchers at Signature Genomic Laboratories, which performs diagnostic genetic testing of chromosome abnormalities in individuals with unexplained physical and developmental disabilities, recently showed that microarray analysis can identify small DNA alterations in individuals with Pitt-Hopkins syndrome, a rare and poorly characterized genetic disorder.
Children with Pitt-Hopkins syndrome usually have severe mental retardation, characteristic unusual facial features, increased risk for seizures, and may have breathing disturbances which can lead to cyanosis. Although the syndrome has only recently been characterized in depth, researchers know it is caused by the presence of only one functioning copy of the gene TCF4 on chromosome 18, which results when the other copy of the gene is mutated or missing. Previous studies have suggested the clinical features associated with Pitt-Hopkins syndrome are independent of the type of genetic anomaly.
In their study, published in the journal Genetics in Medicine, the journal of the American College of Medical Genetics, geneticists at Signature identified seven individuals with a missing copy of a small region on chromosome 18 including TCF4 in their patient. All seven individuals had features consistent with Pitt-Hopkins syndrome, although only three had breathing anomalies, and none had seizures. By comparing their patients with individuals with the syndrome in the scientific literature, the geneticists at Signature determined that, contrary to previous suggestions that the spectrum of clinical features associated with Pitt-Hopkins syndrome was independent of the type of genetic anomaly, individuals with a certain type of gene mutation were more likely to have seizures than individuals with other mutations or deletions.
“Because Pitt-Hopkins syndrome is rare and only recently described in the literature, children with the syndrome may undergo multiple blood draws and expensive evaluations with little chance of diagnosis,” said Dr. Lisa G. Shaffer, Ph.D., President and CEO of Signature and senior author of the study. “Our results show that, because microarray analysis can identify chromosome abnormalities in individuals with nonspecific symptoms, such as developmental delay, without the need for clinical suspicion of a specific disorder, it may allow earlier diagnoses for syndromes such as Pitt Hopkins. This allows for better medical management and appropriate surveillance for the development or presence of specific clinical features, such as seizures and hyperventilation.”
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