Kallmann Syndrome: A Comprehensive Review of Pathophysiology, Clinical Manifestations, and Therapeutic Approaches
Main Article Content
Abstract
Kallmann Syndrome (KS) is a rare genetic disorder characterized by hypogonadotropic hypogonadism (HH) and anosmia or hyposmia due to a defect in the migration of gonadotropin-releasing hormone (GnRH) neurons and olfactory nerve fibers during embryonic development. This syndrome, first described in the 20th century, encompasses a complex interplay of genetic mutations affecting neuronal migration and neuroendocrine regulation. The condition presents a broad spectrum of clinical manifestations, from delayed or absent puberty to infertility, and is frequently associated with additional non-reproductive anomalies, such as sensorineural hearing loss, renal agenesis, or cleft palate. The genetic heterogeneity of KS involves several implicated genes, including KAL1, FGFR1, PROKR2, and CHD7, among others. Diagnostic evaluation typically requires a multidisciplinary approach, integrating genetic testing, hormonal assessments, and neuroimaging to confirm the diagnosis and evaluate associated anomalies. Therapeutic strategies primarily focus on hormonal replacement therapy to induce and maintain secondary sexual characteristics and fertility treatment options for individuals seeking reproductive outcomes. Emerging treatments and the potential use of gene therapy are under investigation, offering new hope for targeted interventions. This review aims to provide a comprehensive overview of Kallmann Syndrome, highlighting its pathophysiology, clinical spectrum, diagnostic challenges, and evolving therapeutic landscape.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
I. Campos Martorell A, Vega Puyal L, Clemente León M, Yeste Fernandez D, Albisu Aparicio MA, Carrascosa Lezcano A. Diagnóstico de síndrome de Kallmann en varones durante el periodo neonatal: revisión de los últimos 15 años. Rev Esp Endocrinol Pediatr 2013;4:48-53.
II. Houston BJ, Riera-Escamilla A, Wyrwoll MJ, Salas-Huetos A, Xavier MJ, Nagirnaja L, et al. A systematic review of the validated monogenic causes of human male infertility: 2020 update and a discussion of emerging gene-disease relationships. Hum Reprod Update. 2021;28:15-29.
III. Kaplan JD, Bernstein JA, Kwan A, Hudgins L. Clues to an early diagnosis of Kallmann syndrome. Am J Med Genet A. 2010;152A:2796-801.
IV. Stamou MI, Georgopoulos NA. Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism. Metab. 2018;86:124-34.
V. Fontecha García de Yébenes M, Hoyos Gurrea R, Iglesias Fernández C, Rodríguez Arnao MD, Rodríguez Sánchez A. Síndrome de Kallmann-Maestre de San Juan. Presentación de 2 casos clínicos. An Pediatr. 2009;71(1):88-9.
VI. Alnæs M, Melle KO. Kallmann syndrome. Tidsskr Nor Legeforen. 2019;139(17).Fu CP, Lee IT. Kallmann syndrome with micropenis. Am J Med Sci. 2018;356(2):e23.
VII. Marhari H, Chahdi Ouazzani FZ, Ouahabi HE, Bouguenouch L. Kallmann-de Morsier syndrome: about 3 cases. Pan Afr Med J.2019;18(33):221.
VIII. Cañete Estrada R, Gil Campos M, Cañete Vázquez MD. Pubertad retrasada. Hipogonadismos. Protoc diagn ter pediatr. 2019;1:253-66.