Balancing Molecular Tools With Clinical Judgment

Genetic testing has transformed pediatric dermatology, offering unprecedented diagnostic clarity for complex and rare conditions. Yet Antonio Torrelo, MD, emphasized at South Beach Symposium and Masters of Pediatric Dermatology 2026 that genetics does not replace clinical expertise—it amplifies it. “Genes don’t diagnose patients,” he said. “Clinicians do.”

For decades, pediatric dermatology has relied on careful visual assessment, pattern recognition, detailed history-taking, and clinicopathologic correlation. These foundational skills remain essential, even as molecular diagnostics become faster, broader, and more accessible. According to Torrelo, the challenge is no longer whether genetic testing is available, but rather knowing when to test, what to test, and how to interpret results responsibly within a clinical framework.

Two complementary diagnostic pathways now dominate modern practice. In the “skin-to-gene” approach, clinical findings guide targeted genetic testing. In the “gene-to-skin” approach, molecular results prompt reexamination of the phenotype and broader systemic evaluation. “Both are valid,” Torrelo noted. “The danger is using either one without thinking.” Without deliberate clinical reasoning, genetic testing risks becoming either underutilized or overapplied.

Several case examples illustrated the value of phenotype-driven testing. In infants presenting with early-onset erythroderma, unusual palmoplantar keratoderma, or distinctive vascular patterns, subtle cutaneous clues narrowed the differential diagnosis and allowed for focused genetic confirmation. Early identification enabled timely intervention, surveillance, and family counseling. In other cases, systemic red flags—such as unexplained bruising, recurrent infections, or failure to thrive—prompted laboratory evaluation before genetic testing revealed underlying immunodeficiency syndromes. “In pediatrics, timing matters,” Torrelo said. “Early diagnosis can be lifesaving.”

A recurring theme in Torrelo’s presentation was the complexity of interpreting variants of uncertain significance (VUS). As genetic panels expand, VUS findings have become increasingly common. “A VUS is not an answer,” he cautioned. These results require careful correlation with clinical features, family history, histopathology, and, in some cases, longitudinal follow-up. Without strong phenotypic expertise, clinicians may overinterpret uncertain findings, leading to unnecessary anxiety or inappropriate management.

At the same time, Torrelo acknowledged the value of broader sequencing strategies when used judiciously. In several examples, pathogenic mutations identified through panel or exome testing prompted clinicians to revisit the physical examination and uncover previously overlooked findings. “Sometimes the gene teaches us what to look for,” he said. This bidirectional process reinforces the dynamic relationship between clinical observation and molecular data.

One notable case involved the identification of a previously unrecognized syndrome associated with mutations in protein kinase D1. The diagnostic journey began with vascular skin findings that, when evaluated alongside genetic results, led to recognition of a broader systemic disorder. “Dermatology often opens the door,” Torrelo observed. “The skin tells the story first.” Such cases highlight the unique role dermatologists play in identifying multisystem disease through cutaneous signs.

Despite the growing power of genetic testing, Torrelo strongly cautioned against indiscriminate use. Genetic results carry implications not only for the patient, but also for parents, siblings, and future family planning. They can introduce psychological stress, uncertainty, and ethical considerations. Clear communication about the purpose, limitations, and possible outcomes of testing is essential. “We have to be very careful about what we promise,” he said. “Not every test gives certainty.”

Judicious testing also has practical implications for health care systems. Broad, untargeted testing can increase costs, generate ambiguous results, and strain follow-up resources. A phenotype-first approach helps ensure that genetic tools are applied where they are most likely to change management, prognosis, or counseling.

Ultimately, Torrelo framed genetic testing as a powerful extension of pediatric dermatology rather than a replacement for its core principles. Precision dermatology depends not on the volume of data generated, but on the clinician’s ability to synthesize molecular findings with careful observation and reasoning. “The best diagnoses still come from thinking,” he concluded. “Genetics doesn’t replace dermatology—it makes it better.”

Reference

1. Torrelo A. Genetic testing in peds. Presented at: South Beach Symposium 2026; February 5-7, 2026; Miami Beach, FL.