Journal of Assisted Reproduction and Genetics

, Volume 36, Issue 12, pp 2481–2484 | Cite as

Live birth in male de novo Kallmann syndrome after cross-generational genetic sequencing

  • Cindy Chan
  • Cheng-Wei Wang
  • Ching-Hui Chen
  • Chi-Huang ChenEmail author
Assisted Reproduction Technologies



To present the first case proposing the use of preimplantation genetic testing for monogeneic disorders for Kallmann syndrome, providing comprehensive care in the genomic era of precision medicine.


Gonadotropin therapy was used for spermatogenesis, followed by in vitro fertilization by intracytoplasmic sperm injection and embryo transfer. Cross-generational targeted next-generation sequencing was then done for genes known to cause Kallmann syndrome.


A heterozygous mutation at codon 102 of the FGFR1 gene was found in the patient, but the father was found to have the same mutation yet is unaffected by Kallmann syndrome. Since no causative mutation was found, a de novo or sporadic mutation was suspected as the cause of Kallmann syndrome in this case.


Comprehensive care must be available for male Kallmann syndrome patients, as treatment should not stop at spermatogenesis, but continue with genetic counseling due to possible inheritance.


Kallmann syndrome Next-generation sequencing Genetic counseling Spermatogenesis 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Young J. Approach to the male patient with congenital hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2012;97(3):707–18.CrossRefGoogle Scholar
  2. 2.
    Young J, Xu C, Papadakis GE, Acierno JS, Maione L, Hietamäki J, et al. Clinical management of congenital hypogonadotropic hypogonadism. Endocr Rev. 2019;40(2):669–710.CrossRefGoogle Scholar
  3. 3.
    Costa-Barbosa FA, Balasubramanian R, Keefe KW, Shaw ND, al-Tassan N, Plummer L, et al. Prioritizing genetic testing in patients with Kallmann syndrome using clinical phenotypes. J Clin Endocrinol Metab. 2013;98(5):E943–53.CrossRefGoogle Scholar
  4. 4.
    Maione L, Dwyer AA, Francou B, Guiochon-Mantel A, Binart N, Bouligand J, et al. Genetics in endocrinology: genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and next-generation sequencing. Eur J Endocrinol. 2018;178(3):R55–r80.CrossRefGoogle Scholar
  5. 5.
    Topaloglu AK. Update on the genetics of idiopathic hypogonadotropic hypogonadism. J Clin Res Pediatr Endocrinol. 2017;9(Suppl 2):113–22.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Gao Y, Yu B, Mao J, Wang X, Nie M, Wu X. Assisted reproductive techniques with congenital hypogonadotropic hypogonadism patients: a systematic review and meta-analysis. BMC Endocr Disord. 2018;18(1):85.CrossRefGoogle Scholar
  7. 7.
    Gardner DK, S.W.I.v.c.o.h.b.I.J.R., Mortimer D, editors. Toward reproductive certainty: fertility and genetics beyond 1999. UK: Parthenon Publishing London; 1999. p. 378-388.Google Scholar
  8. 8.
    The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod, 2011. 26(6): p. 1270-83.Google Scholar
  9. 9.
    Stenson PD, Ball EV, Mort M, Phillips AD, Shiel JA, Thomas NS, et al. Human Gene Mutation Database (HGMD): 2003 update. Hum Mutat. 2003;21(6):577–81.CrossRefGoogle Scholar
  10. 10.
    Kim SH. Congenital hypogonadotropic hypogonadism and Kallmann syndrome: past, present, and future. Endocrinol Metab (Seoul). 2015;30(4):456–66.CrossRefGoogle Scholar
  11. 11.
    Quaynor SD, Bosley ME, Duckworth CG, Porter KR, Kim SH, Kim HG, et al. Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann syndrome. Mol Cell Endocrinol. 2016;437:86–96.CrossRefGoogle Scholar
  12. 12.
    Boehm U, Bouloux PM, Dattani MT, de Roux N, Dodé C, Dunkel L, et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015;11(9):547–64.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Cindy Chan
    • 1
  • Cheng-Wei Wang
    • 1
  • Ching-Hui Chen
    • 1
    • 2
  • Chi-Huang Chen
    • 1
    • 2
    Email author
  1. 1.Division of Reproductive Medicine, Department of Obstetrics and GynecologyTaipei Medical University HospitalTaipeiTaiwan
  2. 2.Department of Obstetrics and Gynecology, School of Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan

Personalised recommendations