Gyula Acsadi, MD, PhD, Editor

For a long time, many childhood developmental and neurologic diseases were characterized as “idiopathic,” but now it is used less often thanks to rapidly increasing genetic discoveries. Since the introduction of cytogenetics in the middle of the twentieth century, the evolution of genetic technologies, from positional cloning to the next-generation sequencing, has allowed us to discover the causes of hundreds of pediatric neurologic diseases. The recognition of genetic and phenotypic variability constantly redefines nomenclature and disease classification. However, a better understanding of molecular mechanism of diseases has been made possible by genetically engineered cell cultures and animals as disease models. This, in turn, provided platforms for screening therapeutic molecules. The rapidly evolving research has led to development of rational therapies for many diseases that were thought to be incurable in the past.

In this special issue of Pediatric Clinics of North America , it is our pleasure to provide updates on various common childhood developmental and neurologic conditions that have directly or indirectly benefited from genome research. For many of these, therapeutic interventions are available or being considered. There is no doubt that our efforts in supportive treatments have improved the quality of life and extended the life expectancy of children suffering from neurologic diseases. Our renewed hope is that new therapies, based on molecular mechanisms, will significantly improve the outcome.

The increasing availability of new genetic tests, such as whole-exome sequencing, is bound to change traditional diagnostic approaches. We will likely order less biochemical, histological, and other neurodiagnostic tests. We will have to tailor the treatments based on individual genotypes. For example, the antisense oligonucleotide-based “exon skipping” treatment for Duchenne muscular dystrophy is designed to treat patients with specific mutations.

In the meantime, considerable limitations exist for the new genetic technologies. Whole-exome sequencing covers only 1.5% of the human genome, and it may miss some large deletions, triplet repeat expansions (eg, CTG repeat expansion in myotonic dystrophy), mutations in introns (eg, regulatory sites), and gene promoters. Epigenetic regulation is important in the phenotypic expression of some neurologic diseases, such as chromosome 15–related conditions. Testing for these requires additional laboratory processes. Whole-genome sequencing will further improve the genetic testing of neurologic diseases; however, the differentiation of disease-causing genetic mutations from benign or irrelevant DNA alterations requires the aid of genetic specialists. This is a very time-consuming task that is not reimbursed by most insurance carriers in the United States. Another significant problem regarding test results is dealing with unexpected disease-causing gene abnormalities, which may have a significant impact for the future health of the individual.

I am delighted to present thirteen excellent review articles written by well-recognized experts in the field of Pediatric Neurology and Developmental Pediatrics. We trust that these articles are going to be helpful resources for the practicing pediatric specialists.