Topic: Advances in the Diagnosis, Management, and Therapeutics of Kallmann Syndrome with Insights into Genetic Etiology

Kallmann syndrome (KS) is a rare genetic disorder characterized by congenital hypogonadotropic hypogonadism (CHH) and anosmia or hyposmia. It represents a prototypical disorder of gonadotropin-releasing hormone (GnRH) neuronal development and function. With an estimated prevalence of 1 in 8,000 males and 1 in 40,000 females, KS remains a significant cause of absent or delayed puberty and infertility. Formerly understudied and frequently misdiagnosed due to its heterogeneous clinical presentation, KS has garnered increasing attention from basic science researchers and clinicians in recent years, driven by breakthroughs in genetic sequencing technologies and the development of targeted therapeutic strategies such as pulsatile GnRH replacement therapy.

Despite these advances, substantial unmet needs remain in the early diagnosis, personalized management protocols, and comprehensive therapies that address not only the reproductive dysfunction but also broader health and quality-of-life concerns. These include optimizing fertility induction, managing long-term sequelae of sex steroid deficiency (e.g., osteoporosis), and addressing the psychological and social challenges faced by affected individuals. The integration of next-generation sequencing into clinical practice has revolutionized diagnosis, enabling precise genetic counseling and prognostication. Simultaneously, advances in pulsatile GnRH therapy and assisted reproductive technologies have improved fertility outcomes.

In this Special Issue of Rare Diseases and Orphan Drugs Journal, we invite authors to explore the latest frontiers in KS research and clinical care, highlighting the journey from a complex genetic puzzle to an emerging model of precision medicine.

We welcome Original Research Articles, Review Articles, and Brief Communications. Topics planned for coverage include:

● From Phenotype to Genotype: The expanding genetic landscape of KS and its implications for diagnosis and classification;

● Inducing Puberty: Optimization of sex steroid replacement regimens and pulsatile GnRH therapy across the lifespan;

● Restoring Fertility: Advances in spermatogenesis and ovulation induction, and the role of assisted reproductive technologies;

● Beyond the Gonads: Management of comorbidities (e.g., osteoporosis, metabolic disturbances, renal anomalies) and non-reproductive features;

● The Olfactory Dimension: Mechanisms underlying anosmia and emerging prospects for therapeutic intervention;

● Brain Development and Beyond: Neurocognitive, psychiatric, and quality-of-life aspects in individuals with KS;

● Inclusive care for diverse KS populations: Gender-specific considerations and equitable access to therapies;

● Emerging Therapies on the Horizon: Gene therapy, cell-based approaches, and novel pharmacological targets.