Kallmann Syndrome and Idiopathic Hypogonadotropic Hypogonadism Differential Diagnoses

1. Bonomi M, Libri DV, Guizzardi F, Guarducci E, Maiolo E, Pignatti E, et al. New understandings of the genetic basis of isolated idiopathic central hypogonadism. Asian J Androl. 2012 Jan. 14(1):49-56. [QxMD MEDLINE Link].

2. Dode C, Levilliers J, Dupont JM, et al. Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nat Genet. 2003 Apr. 33(4):463-5. [QxMD MEDLINE Link].

3. Silveira LF, Latronico AC. Approach to the patient with hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2013 May. 98(5):1781-8. [QxMD MEDLINE Link].

4. Pitteloud N, Quinton R, Pearce S, et al. Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism. J Clin Invest. 2007 Feb. 117(2):457-63. [QxMD MEDLINE Link]. [Full Text].

5. Monnier C, Dode C, Fabre L, et al. PROKR2 missense mutations associated with Kallmann syndrome impair receptor signalling-activity. Hum Mol Genet. 2008 Sep 29. [QxMD MEDLINE Link].

6. Abreu AP, Trarbach EB, de Castro M, et al. Loss-of-function mutations in the genes encoding prokineticin-2 or prokineticin receptor-2 cause autosomal recessive Kallmann syndrome. J Clin Endocrinol Metab. 2008 Oct. 93 (10):4113-8. [QxMD MEDLINE Link].

7. Pitteloud N, Zhang C, Pignatelli D, et al. Loss-of-function mutation in the prokineticin 2 gene causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci U S A. 2007 Oct 30. 104(44):17447-52. [QxMD MEDLINE Link]. [Full Text].

8. Dode C, Teixeira L, Levilliers J, et al. Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. PLoS Genet. 2006 Oct 20. 2(10):e175. [QxMD MEDLINE Link]. [Full Text].

9. Canto P, Munguía P, Söderlund D, et al. Genetic analysis in patients with Kallmann syndrome: coexistance of mutations in prokineticin receptor 2 and KAL1. J Androl. 2008 Aug 21. [QxMD MEDLINE Link].

10. Merke DP, Tajima T, Baron J, et al. Hypogonadotropic hypogonadism in a female caused by an X-linked recessive mutation in the DAX1 gene. N Engl J Med. 1999. 340(16):1248-52. [QxMD MEDLINE Link].

11. Clement K, Vaisse C, Lahlou N, et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature. 1998 Mar 26. 392(6674):398-401. [QxMD MEDLINE Link].

12. Pralong FP, Gomez F, Castillo E, et al. Complete hypogonadotropic hypogonadism associated with a novel inactivating mutation of the gonadotropin-releasing hormone receptor. J Clin Endocrinol Metab. 1999 Oct. 84(10):3811-6. [QxMD MEDLINE Link].

13. Seminara SB, Messager S, Chatzidaki EE, et al. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003 Oct 23. 349(17):1614-27. [QxMD MEDLINE Link]. [Full Text].

14. Silveira LG, Latronico AC, Seminara SB. Kisspeptin and clinical disorders. Adv Exp Med Biol. 2013. 784:187-99. [QxMD MEDLINE Link].

15. Dhillo WS, Chaudhri OB, Patterson M, et al. Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab. 2005 Dec. 90(12):6609-15. [QxMD MEDLINE Link].

16. Gottsch ML, Cunningham MJ, Smith JT, et al. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology. 2004 Sep. 145(9):4073-7. [QxMD MEDLINE Link]. [Full Text].

17. Miura K, Acierno JS, Seminara SB. Characterization of the human nasal embryonic LHRH factor gene, NELF, and a mutation screening among 65 patients with idiopathic hypogonadotropic hypogonadism (IHH). J Hum Genet. 2004. 49(5):265-8. [QxMD MEDLINE Link].

18. Young J, Metay C, Bouligand J, Tou B, Francou B, Maione L, et al. SEMA3A deletion in a family with Kallmann syndrome validates the role of semaphorin 3A in human puberty and olfactory system development. Hum Reprod. 2012 May. 27 (5):1460-5. [QxMD MEDLINE Link].

19. Tornberg J, Sykiotis GP, Keefe K, Plummer L, Hoang X, Hall JE, et al. Heparan sulfate 6-O-sulfotransferase 1, a gene involved in extracellular sugar modifications, is mutated in patients with idiopathic hypogonadotrophic hypogonadism. Proc Natl Acad Sci U S A. 2011 Jul 12. 108 (28):11524-9. [QxMD MEDLINE Link].

20. Miraoui H, Dwyer AA, Sykiotis GP, et al. Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet. 2013 May 2. 92 (5):725-43. [QxMD MEDLINE Link].

21. Kim HG, Ahn JW, Kurth I, Ullmann R, Kim HT, Kulharya A, et al. WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet. 2010 Oct 8. 87 (4):465-79. [QxMD MEDLINE Link].

22. Salian-Mehta S, Xu M, Knox AJ, Plummer L, Slavov D, Taylor M, et al. Functional consequences of AXL sequence variants in hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2014 Apr. 99 (4):1452-60. [QxMD MEDLINE Link].

23. Pingault V, Bodereau V, Baral V, Marcos S, Watanabe Y, Chaoui A, et al. Loss-of-function mutations in SOX10 cause Kallmann syndrome with deafness. Am J Hum Genet. 2013 May 2. 92 (5):707-24. [QxMD MEDLINE Link].

24. Turan I, Hutchins BI, Hacihamdioglu B, Kotan LD, Gurbuz F, Ulubay A, et al. CCDC141 Mutations in Idiopathic Hypogonadotropic Hypogonadism. J Clin Endocrinol Metab. 2017 Jun 1. 102 (6):1816-1825. [QxMD MEDLINE Link].

25. Seminara SB, Hayes FJ, Crowley WF Jr. Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmann''''s syndrome): pathophysiological and genetic considerations. Endocr Rev. 1998 Oct. 19(5):521-39. [QxMD MEDLINE Link]. [Full Text].

26. Trarbach EB, Silveira LG, Latronico AC. Genetic insights into human isolated gonadotropin deficiency. Pituitary. 2007. 10(4):381-91. [QxMD MEDLINE Link].

27. Seminara SB, Achermann JC, Genel M, et al. X-linked adrenal hypoplasia congenita: a mutation in DAX1 expands the phenotypic spectrum in males and females. J Clin Endocrinol Metab. 1999 Dec. 84(12):4501-9. [QxMD MEDLINE Link].

28. Beranova M, Oliveira LM, Bedecarrats GY, et al. Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2001 Apr. 86(4):1580-8. [QxMD MEDLINE Link].

29. Patil VA, Lila AR, Shah N, et al. Genetic spectrum of Kallmann syndrome: Single-center experience and systematic review. Clin Endocrinol (Oxf). 2022 Dec. 97 (6):804-13. [QxMD MEDLINE Link].

30. Caronia LM, Martin C, Welt CK, Sykiotis GP, Quinton R, Thambundit A, et al. A genetic basis for functional hypothalamic amenorrhea. N Engl J Med. 2011 Jan 20. 364(3):215-25. [QxMD MEDLINE Link]. [Full Text].

31. Fromantin M, Gineste J, Didier A, et al. [Impuberism and hypogonadism at induction into military service. Statistical study]. Probl Actuels Endocrinol Nutr. 1973 May 3. 16:179-99. [QxMD MEDLINE Link].

32. Filippi G. Klinefelter's syndrome in Sardinia. Clinical report of 265 hypogonadic males detected at the time of military check-up. Clin Genet. 1986 Oct. 30(4):276-84. [QxMD MEDLINE Link].

33. Sonne J, Lopez-Ojeda W. Kallmann Syndrome. StatPearls. 2023 Jan. [QxMD MEDLINE Link]. [Full Text].

34. Raivio T, Falardeau J, Dwyer A, et al. Reversal of idiopathic hypogonadotropic hypogonadism. N Engl J Med. 2007 Aug 30. 357(9):863-73. [QxMD MEDLINE Link]. [Full Text].

35. Fraietta R, Zylberstejn DS, Esteves SC. Hypogonadotropic hypogonadism revisited. Clinics (Sao Paulo). 2013. 68 Suppl 1:81-8. [QxMD MEDLINE Link]. [Full Text].

36. Nishio H, Mizuno K, Moritoki Y, Kamisawa H, Kojima Y, Mizuno H, et al. Clinical features and testicular morphology in patients with Kallmann syndrome. Urology. 2012 Mar. 79(3):684-6. [QxMD MEDLINE Link].

37. Swee DS, Quinton R, Maggi R. Recent advances in understanding and managing Kallmann syndrome. Fac Rev. 2021. 10:37. [QxMD MEDLINE Link]. [Full Text].

38. Quinton R, Duke VM, de Zoysa PA, et al. The neuroradiology of Kallmann's syndrome: a genotypic and phenotypic analysis. J Clin Endocrinol Metab. 1996 Aug. 81(8):3010-7. [QxMD MEDLINE Link]. [Full Text].

39. Raivio T, Wikstrom AM, Dunkel L. Treatment of gonadotropin-deficient boys with recombinant human FSH: long-term observation and outcome. Eur J Endocrinol. 2007 Jan. 156(1):105-11. [QxMD MEDLINE Link].

Nicholas A Tritos, MD, DSc, MMSc, FACP, FACE Associate Professor of Medicine, Harvard Medical School; Associate in Medicine, Neuroendocrine Clinical Center, Massachusetts General Hospital

Nicholas A Tritos, MD, DSc, MMSc, FACP, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Medical Association, Endocrine Society, Massachusetts Medical Society, Pituitary Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Nutrition, American Society for Bone and Mineral Research, International Society for Clinical Densitometry, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, Endocrine Society

Disclosure: Nothing to disclose.

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for Physician Leadership, American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society, International Society for Clinical Densitometry, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Ghassem Pourmotabbed, MD, MD

Ghassem Pourmotabbed, MD, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Endocrine Society

Disclosure: Nothing to disclose.

• Print this section
• Print the entire contents of
• Print the entire contents of article