Genetic

The Rare Responsibility: The Silent Instructor

Dear Impossible Readers,

Genetic rare diseases form a unique and often misunderstood group within rare medicine. Unlike disorders limited to a single organ system, these diseases originate at the molecular level, in DNA itself. They can affect nearly any tissue in the body. A single gene mutation may disrupt development, metabolism, neurological function, or cellular maintenance, sometimes all at once. This fundamental overlap explains why rare genetic diseases often defy traditional medical classifications yet share common diagnostic and therapeutic challenges. Recognising these conditions as a category helps patients, families, and clinicians focus on the root causes rather than just the symptoms.

The diversity within this category is remarkable. Fibrodysplasia Ossificans Progressiva (FOP) is caused by a signalling mutation that transforms soft tissue into bone. Hutchinson–Gilford Progeria Syndrome (HGPS) results from a defect in nuclear structure that accelerates ageing. Congenital Insensitivity to Pain with Anhidrosis (CIPA) arises from the failure of sensory neurons to develop, leaving patients unable to feel pain or regulate temperature. Alkaptonuria is a metabolic disorder caused by an enzyme deficiency, which leads to pigment accumulation in connective tissues. Finally, Fatal Familial Insomnia (FFI) is driven by toxic protein misfolding in the brain. These diseases are rarely clinically similar, yet all stem from specific genetic errors, emphasising the central role of DNA in rare diseases and highlighting the wide range of mechanisms that genetics can disrupt.

Current treatments are mostly supportive and vary greatly. FOP requires careful handling of trauma and pain, but no cure exists. HGPS patients benefit from cardiovascular and growth-focused care. CIPA care concentrates on preventing injuries and overheating. Alkaptonuria can be managed through dietary restrictions and symptom relief, while FFI has no effective therapy beyond palliative care. Overall, most interventions target complications rather than fixing the underlying genetic defect. This variability reflects both the complexity of human genetics and the historical limitations of medicine in addressing DNA-level disorders.

Genetic rare diseases are at the forefront of medical innovation. Gene therapy and gene editing offer the potential to correct or compensate for defective genes. RNA-based drugs may silence harmful mutations or restore missing proteins. Advances in genomic sequencing, early diagnosis, and personalised medicine are paving the way for treatments that could slow or even prevent disease progression at a molecular level. Although most of these therapies are still experimental, they represent a fundamental shift from symptom management towards directly addressing the root causes.

For patients and families today, the most immediate opportunities lie in personalised medicine. Genetic testing can identify the specific mutation causing a disorder, enabling treatments to be customised to an individual’s molecular profile. Clinical trials increasingly focus on specific gene variants, providing access to therapies tailored to a patient’s unique genetic makeup. Multidisciplinary care remains vital, but the combination of early diagnosis, detailed genetic information, and emerging targeted therapies is already improving outcomes. By understanding rare genetic diseases at the molecular level, patients and clinicians can make informed, proactive decisions that translate personalised medicine into practical strategies today.

Toward a decoded future,
Yours Possibly

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Further Reading

Bernardini, G., Braconi, D., Zatkova, A., Sireau, N., Kujawa, M.J., Introne, W.J., Spiga, O., Geminiani, M., Gallagher, J.A., Ranganath, L.R. and Santucci, A., 2024. Alkaptonuria. Nature Reviews Disease Primers, 10(1), p.16.
Choi, M., 2025. Editorial for the special collection: frontiers in rare disease genetics. Genomics & Informatics, 23(1), p.9.
Harrak, H., Rhee, S., Souttou, A., O’Meara, S.J. and Knox, C., 2025. Understanding the clinical morbidity and mortality of fibrodysplasia ossificans progressiva: a systematic literature review. Orphanet Journal of Rare Diseases, 20(1), p.262.
Hong, J., Lee, D., Hwang, A., Kim, T., Ryu, H.Y. and Choi, J., 2024. Rare disease genomics and precision medicine. Genomics & Informatics, 22(1), p.28.
Ikrama, M., Usama, M., Haider, M.H., Israr, S. and Humayon, M., 2024. Congenital insensitivity to pain with anhidrosis: A literature review and the advocacy for stem cell therapeutic interventions. Therapeutic Advances in Rare Disease, 5, p.26330040241292378.
Khan, Z., Sankari, A. and Bollu, P.C., 2024. Fatal familial insomnia. In StatPearls [Internet]. StatPearls Publishing.
Khawaja, S., Ali, R.H., Ahmed, I. and Umair, M., 2025. Gene Therapy in Rare Genetic Disorders: Current Progress and Future Perspectives. Current Genomics.
Rodríguez-Blanque, R., Nielsen, L.M., Piqueras-Sola, B., Sánchez-García, J.C., Cortés-Martín, C., Reinoso-Cobo, A. and Cortés-Martín, J., 2024. A systematic review of congenital insensitivity to pain, a rare disease. Journal of Personalized Medicine, 14(6), p.570.
Zhou, X. and Song, J., 2025. Unraveling the mysteries of Hutchinson-Gilford progeria syndrome: a comprehensive review of LMNA gene mutations. Biogerontology, 26(5), p.186.