A rare case of Kallmann syndrome in a female with pulmonary valve stenosis: Coincidence or genetic link?

##plugins.themes.academic_pro.article.sidebar##

Published May 1, 2025
https://doi.org/10.62438/tunismed.v103i5.5783
Download
pdf
Vol. 103 No. 5 (2025): Tunis Med May 2025

##plugins.themes.academic_pro.article.main##

Mariam Hamaichat
Endocrinology Department of Souss Massa University Hospital Centre, Agadir, Morocco.
Hajar Srifi
Endocrinology Department of Mohamed V Military Training Hospital, Rabat, Morocco
Ahmed Anas Guerboub
Endocrinology Department of Mohamed V Military Training Hospital, Rabat, Morocco.

Abstract

Introduction: Kallmann De Morsier syndrome (KS) is a rare genetic disorder characterized by congenital gonadotropic deficiency alongside anosmia or hyposmia, with a lower prevalence in females. Diagnosis relies on clinical and biological assessment, confirmed through pituitary magnetic resonance imaging (MRI). Cardiac involvement in this syndrome is uncommon, with only a few cases documented in the literature.


Observation: We reported the case of a 22-year-old female with a history of pulmonary valve stenosis for which she underwent balloon dilatation at the age of five years. She presented with primary amenorrhoea and a history of anosmia was noted. Hormonal investigations revealed hypogonadotropic hypogonadism and a hypothalamic-pituitary MRI identified complete agenesis of the olfactory bulbs. A diagnosis of KS was made. Genetic testing for the KAL1 gene was negative. The patient was put on hormone replacement therapy in order to achieve her puberty and promote general well-being


Conclusion: This case represents the first reported association between KS and pulmonary valve stenosis, highlighting the need for further molecular biological research to explore other genes that may explain this connection

Keywords:

Genetic testing, heart defects, hypogonadotropic hypogonadism, olfactory bulb agenesis

##plugins.themes.academic_pro.article.details##

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

References

  1. Cho HJ, Shan Y, Whittington NC, Wray S. Nasal placode development, GnRH neuronal migration and Kallmann syndrome. Front Cell Dev Biol. 2019;11(7):121.
  2. Chamseddin BH, Berg EE, Shah G, Mitchell RB. Anosmia in an adolescent. Ear Nose Throat J. 2019;98(3):129-130.
  3. Stamou MI, Georgopoulos NA. Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism. Metabolism. 2018;86:124-134.
  4. Sonne J, Leslie SW, Lopez-Ojeda W. Kallmann Syndrome. 2024 Dec 11. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–.
  5. Marhari H, Chahdi Ouazzani FZ, Ouahabi HE, Bouguenouch L. Kallmann-de Morsier syndrome: about 3 cases. Pan Afr Med J. 2019;18;33:221.
  6. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;44(235):291-303.
  7. Rosenberg SM, Riddick DH. Dynamic pituitary testing in a female with Kallman's syndrome and associated cardiac anomaly. Obstet Gynecol. 1976 Aug; 48(2):230-3.
  8. Gauthier, G. La dysplasie olfacto-génitale. Acta Neurovegetativa.1960;21: 345–394.
  9. Kemmann E, Conrad P, Jones JR. Cardiac abnormalities in female hypogonadotropic hypogonadism with anosmia. Am J Obstet Gynecol. 1980;136(7):964-6.
  10. Gore MR. Association of olfactory neuropathy spectrum disorder and Wolff-Parkinson-White syndrome: A Report of a case. Clin Case Rep. 2020;8(9):1638-1641.
  11. Bennani G, Zahri S, Khaldi M, Benouna G, Drighil A, Habbal R. Unusual coexistence of restrictive heart disease and Kallmann syndrome: a case report. Egypt Heart J. 2024;76(1):50.
  12. Bouhlel I, Ajmi H, Slim M, Gribaa R, Naffati E. Immediate results of balloon valvuloplasty in congenital pulmonary valve stenosis. Tunis Med. 2021;99(2):291-297.
  13. Weaver KN, Chen J, Shikany A, White PS, Prada CE, Gelb BD, et al; Pediatric cardiac genomics consortium investigators. Prevalence of genetic diagnoses in a cohort with valvar pulmonary stenosis. Circ Genom Precis Med. 2022;15(4):e003635.
  14. Wen J, Pan L, Xu X, Wang J, Hu C. Clinical data and genetic mutation in Kallmann syndrome with CHARGE syndrome: Case report and pedigree analysis. Medicine (Baltimore). 2018;97(27):e11284.
  15. Dai J, Zeng J, Tan H, Cai X, Wu B. Novel 12 Mb interstitial deletion of chromosome 8p11.22-p21.2: a case report. BMC Med Genomics. 2022 Jun 6;15(1):126.
  16. Maione L, Brailly-Tabard S, Nevoux J, Bouligand J, Young J. Reversal of congenital hypogonadotropic hypogonadism in a man with Kallmann syndrome due to SOX10 mutation. Clin Endocrinol (Oxf). 2016;85(6):988–989.
  17. Zhang W, Xiao L, Chen B, Xu Y, Yan N. 22q12.3-q13.1 microdeletion including SOX10 causes atypical Waardenburg syndrome. Eur J Ophthalmol. 2021;31(4):2127-2134.
  18. Jacques Y, Cheng X, Georgios EP, et al. Clinical Management of Congenital Hypogonadotropic Hypogonadism, Endocr Rev. 2019;40(2):669–710.
  19. Youssef MA, Abou-Setta AM, Lam WS. Recombinant versus urinary human chorionic gonadotrophin for final oocyte maturation triggering in IVF and ICSI cycles. Cochrane Database Syst Rev. 2016;4:CD003719.
  20. Bry-Gauillard H, Larrat-Ledoux F, Levaillant JM, et al. Anti-Müllerian hormone and ovarian morphology in women with isolated hypogonadotropic hypogonadism/Kallmann syndrome: effects of recombinant human FSH. J Clin Endocrinol Metab. 2017;102(4):1102–1111.