Topic: Human Genetics 2025: From Developmental Disorders to Structural Genomics

Developmental and structural disorders encompass a broad and diverse group of conditions that arise during prenatal or early postnatal development, often manifesting as intellectual disability, global developmental delay, congenital anomalies, epilepsy, craniofacial dysmorphisms, or complex syndromic features. Although individually rare, these disorders collectively impose a major clinical and societal burden, ranking among the leading causes of pediatric hospitalization, long-term disability, and early mortality.

Recent advances in genomic technologies have revolutionized the diagnosis and management of these conditions. Chromosomal microarray analysis, exome sequencing, and more recently, genome sequencing have dramatically improved diagnostic yields - reaching 40–60% in certain cohorts - and resolved challenging cases where conventional testing failed.

A timely and accurate genetic diagnosis is critical. It provides clarity for families, ends prolonged diagnostic odysseys, and enables access to multidisciplinary care, precision therapies, and informed reproductive decision making. Moreover, it facilitates risk assessment for future offspring and supports participation in clinical trials and patient support networks.

Beyond immediate clinical benefits, elucidating the genetic causes of developmental and structural disorders offers fundamental insights into human development, brain function, and organogenesis, and often sheds light on more common diseases. Rare disease research has uncovered key developmental genes, enhanced our understanding of dosage sensitivity, and driven innovation in diagnostics, gene therapy, and genome editing.

Despite these advances, significant challenges persist. Many patients remain undiagnosed even after exhaustive testing, and interpreting variants of uncertain significance remains difficult, particularly in underrepresented populations. Global inequities in access to genetic testing and counseling further exacerbate these gaps, as most genomic data currently derive from populations of European ancestry, limiting generalizability and equity in care.

This Special Issue brings together cutting-edge research, clinical insights, and translational advances in the genetic diagnosis of developmental and structural disorders. We welcome original research articles, case series, reviews, case reports, and perspectives on the following themes:

1. Novel genomic and multi-omics approaches for diagnosis;

2. Identification of new disease genes and genotype–phenotype correlations;

3. Diagnostic yield and cost-effectiveness of exome or genome sequencing in clinical practice;

4. Interpretation and clinical impact of variants of uncertain significance;

5. Prenatal genetic diagnosis and challenges in early prediction of structural anomalies;

6. Functional studies supporting variant classification and elucidating disease mechanisms;

7. Ethical, legal, and social considerations in pediatric genomic diagnostics.

By fostering dialogue among researchers, clinicians, and policymakers, this issue aims to advance a more comprehensive, inclusive, and clinically actionable understanding of these disorders.

As Guest Editor, I extend my sincere thanks to all contributing authors, peer reviewers, and the Editorial Board of Journal of Translational Genetics and Genomics. I hope this collection will inspire continued research, innovation, and advocacy in support of patients and families affected by developmental and structural disorders worldwide.

Genetic diagnosis, developmental disorders, structural anomalies, clinical exome sequencing, prenatal genomics, genotype–phenotype correlation, pediatric genetics, congenital malformations, rare disease, molecular diagnostics