Male hypogonadotropic hypogonadism in various genetic disorders

Sylwiusz Niedobylski, Katarzyna Laszczak, Konrad Warchoł, Aleksandra Marczak, Maciej Dobosz, Marcin Lewicki, Ewa Obel



Introduction and purpose: Male hypogonadism is diagnosed in patients with total testosterone under 9-12nmol/L (250-350ng/dl) in serum which is associated with numerous symptoms which can severely lower the quality of patients life. Due to the cause and associated levels of gonadotropins it can be divided to hypergonadotropic and hypogonadotropic hypogonadism. Hypogonadotropic hypogonadism occurs far less often, but it’s considered to remain underdiagnosed. The purpose of this study is to review most of the inborn diseases that involve hypogonadotropic hypogonadism as one of their components.

Current state of knowledge: Patients with Kallmann syndrome constitute the majority of confirmed hypogonadotropic hypogonadism cases, however due to variable epidemiological data and differing diagnosing processes the exact incidence cannot be estimated – it ranges from 1 in 85 000, to 1 in 5000 males and about 3-4 times less often in women. Other conditions that can occur with hypogonadotropic hypogonadism are Isolated Gonadotropin-Releasing Hormone deficiency, Gonadotropin disorders, Prader-Willi Syndrome, some pleiotropic syndromes like CHARGE syndrome, Patau syndrome, Pfeiffer syndrome, Hartsfield syndrome, Waardenburg syndrome, Bardet-Biedl syndrome, or other syndromes. The evaluation and treatment of some of these conditions does not involve hypogonadism or other gonadal disorders due to short lifespan, which cause the underestimations in hypogonadism morbidity.

Conclusions: Regardless of lower incidence of hypogonadotropic hypogonadism compared to hypergonadotropic type, endocrinologists should stay aware of its under-diagnosis and actively search for signs of low gonadotropic hormones and gonadotropin-releasing hormone levels in hypogonadal patients.


Hypogonadism; hypogonadotropic; testosterone; genetic disorder; Kallmann syndrome

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A. Richard-Eaglin, “Male and Female Hypogonadism,” Nursing Clinics of North America, vol. 53, no. 3, pp. 395–405, Sep. 2018.

S. Basaria, “Male hypogonadism,” The Lancet, vol. 383, no. 9924, pp. 1250–1263, Apr. 2014.

L. F. G. Silveira, G. S. MacColl, and P. M. G. Bouloux, “Hypogonadotropic Hypogonadism,” Seminars in Reproductive Medicine, vol. 20, no. 4, pp. 327–338, 2002.

T. Mulligan, M. F. Frick, Q. C. Zuraw, A. Stemhagen, and C. Mcwhirter, “Prevalence of hypogonadism in males aged at least 45 years: the HIM study,” International Journal of Clinical Practice, vol. 60, no. 7, pp. 762–769, Oct. 2008.

R. Fraietta, D. Zylberstejn, and S. Esteves, “Hypogonadotropic Hypogonadism Revisited,” Clinics, vol. 68, no. S1, pp. 81–88, Mar. 2013.

S. R. Howard and L. Dunkel, “Management of hypogonadism from birth to adolescence,” Best Practice & Research Clinical Endocrinology & Metabolism, vol. 32, no. 4, pp. 355–372, Aug. 2018.

N. Makhsida, J. Shah, G. Yan, H. Fisch, and R. Shabsigh, “Hypogonadism and metabolic syndrome: implications for testosterone therapy,” Journal of Urology, vol. 174, no. 3, pp. 827–834, sep. 2005.

S. Dhindsa, H. Ghanim, M. Batra, and P. Dandona, “Hypogonadotropic Hypogonadism in Men With Diabesity,” Diabetes Care, vol. 41, no. 7, pp. 1516–1525, Jun. 2018.

U. Boehm et al., “European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment,” Nature Reviews Endocrinology, vol. 11, no. 9, pp. 547–564, Jul. 2015.

J. Young et al., “Clinical Management of Congenital Hypogonadotropic Hypogonadism,” Endocrine Reviews, vol. 40, no. 2, pp. 669–710, Jan. 2019.

A. K. Topaloğlu, “Update on the Genetics of Idiopathic Hypogonadotropic Hypogonadism,” Journal of Clinical Research in Pediatric Endocrinology, pp. 113–122, Jan. 2018.

V. Surampudi and R. S. Swerdloff, “Hypogonadotropic and Hypergonadotropic Hypogonadism,” Testosterone, pp. 133–145, 2017.

A. A. Dwyer et al., “Functional Hypogonadotropic Hypogonadism in Men: Underlying Neuroendocrine Mechanisms and Natural History,” The Journal of Clinical Endocrinology & Metabolism, vol. 104, no. 8, pp. 3403–3414, Mar. 2019.

L. Antonio, S. Caerels, F. Jardi, E. Delaunay, and D. Vanderschueren, “Testosterone replacement in congenital hypogonadotropic hypogonadism maintains bone density but has only limited osteoanabolic effects,” Andrology, vol. 7, no. 3, pp. 302–306, Mar. 2019.

X. Yang, Q. Lin, X. HU, W. Xu, and H. R. Deng, “Association Between Body Fat Mass and Plasma Insulin Level in the Male Patients with Idiopathic Hypogonadotropic Hypogonadism and Normal Glucose Tolerance,” Diabetes, vol. 67, no. Supplement 1, pp. 1972-P, May 2018.

T. S. Han and P. M. G. Bouloux, “What is the optimal therapy for young males with hypogonadotropic hypogonadism?,” Clinical Endocrinology, vol. 72, no. 6, pp. 731–737, Nov. 2009.

C. Dodé and J.-P. Hardelin, ‘Kallmann syndrome’, Eur. J. Hum. Genet., vol. 17, no. 2, pp. 139–146, Feb. 2009, doi: 10.1038/ejhg.2008.206.

E.-M. Laitinen et al., ‘Incidence, Phenotypic Features and Molecular Genetics of Kallmann Syndrome in Finland’, Orphanet J. Rare Dis., vol. 6, p. 41, Jun. 2011, doi: 10.1186/1750-1172-6-41.

M. Fromantin, J. Gineste, A. Didier, and J. Rouvier, ‘[Impuberism and hypogonadism at induction into military service. Statistical study]’, Probl. Actuels Endocrinol. Nutr., vol. 16, pp. 179–199, May 1973.

G. Filippi, ‘Klinefelter’s syndrome in Sardinia. Clinical report of 265 hypogonadic males detected at the time of military check-up’, Clin. Genet., vol. 30, no. 4, pp. 276–284, Oct. 1986.

P. E. Forni, C. Taylor-Burds, V. S. Melvin, T. Williams, T. Williams, and S. Wray, ‘Neural crest and ectodermal cells intermix in the nasal placode to give rise to GnRH-1 neurons, sensory neurons, and olfactory ensheathing cells’, J. Neurosci. Off. J. Soc. Neurosci., vol. 31, no. 18, pp. 6915–6927, May 2011, doi: 10.1523/JNEUROSCI.6087-10.2011.

P. E. Forni and S. Wray, ‘GnRH, anosmia and hypogonadotropic hypogonadism – Where are we?’, Front. Neuroendocrinol., vol. 36, pp. 165–177, Jan. 2015, doi: 10.1016/j.yfrne.2014.09.004.

U. Boehm et al., ‘European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment’, Nat. Rev. Endocrinol., vol. 11, no. 9, pp. 547–564, Sep. 2015, doi: 10.1038/nrendo.2015.112.

M. Schwanzel-Fukuda, D. Bick, and D. W. Pfaff, ‘Luteinizing hormone-releasing hormone (LHRH)-expressing cells do not migrate normally in an inherited hypogonadal (Kallmann) syndrome’, Brain Res. Mol. Brain Res., vol. 6, no. 4, pp. 311–326, Dec. 1989, doi: 10.1016/0169-328x(89)90076-4.

C. Dodé et al., ‘Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome’, Nat. Genet., vol. 33, no. 4, pp. 463–465, Apr. 2003, doi: 10.1038/ng1122.

J. Tornberg 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., vol. 108, no. 28, pp. 11524–11529, Jul. 2011, doi: 10.1073/pnas.1102284108.

H. Miraoui et al., ‘Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 Are Identified in Individuals with Congenital Hypogonadotropic Hypogonadism’, Am. J. Hum. Genet., vol. 92, no. 5, pp. 725–743, May 2013, doi: 10.1016/j.ajhg.2013.04.008.

T. Ogata, I. Fujiwara, E. Ogawa, N. Sato, T. Udaka, and K. Kosaki, ‘Kallmann Syndrome Phenotype in a Female Patient with CHARGE Syndrome and CHD7 Mutation’, Endocr. J., vol. 53, no. 6, pp. 741–743, 2006, doi: 10.1507/endocrj.K06-099.

R. Balasubramanian et al., ‘Functionally compromised CHD7 alleles in patients with isolated GnRH deficiency’, Proc. Natl. Acad. Sci., vol. 111, no. 50, pp. 17953–17958, Dec. 2014, doi: 10.1073/pnas.1417438111.

V. Pingault et al., ‘Loss-of-Function Mutations in SOX10 Cause Kallmann Syndrome with Deafness’, Am. J. Hum. Genet., vol. 92, no. 5, pp. 707–724, May 2013, doi: 10.1016/j.ajhg.2013.03.024.

R. J. Santen and C. A. Paulsen, ‘Hypogonadotropic eunuchoidism. I. Clinical study of the mode of inheritance’, J. Clin. Endocrinol. Metab., vol. 36, no. 1, pp. 47–54, Jan. 1973, doi: 10.1210/jcem-36-1-47.

J. M. Lieblich, A. D. Rogol, B. J. White, and S. W. Rosen, ‘Syndrome of anosmia with hypogonadotropic hypogonadism (kallmann syndrome): Clinical and laboratory studies in 23 cases’, Am. J. Med., vol. 73, no. 4, pp. 506–519, Oct. 1982, doi: 10.1016/0002-9343(82)90329-1.

G. De Morsier and G. Gauthier, ‘[OLFACTO-GENITAL DYSPLASIA]’, Pathol. Biol., vol. 11, pp. 1267–1272, Nov. 1963.

J. P. Hardelin et al., ‘Heterogeneity in the mutations responsible for X chromosome-linked Kallmann syndrome’, Hum. Mol. Genet., vol. 2, no. 4, pp. 373–377, Apr. 1993, doi: 10.1093/hmg/2.4.373.

W. Reardon, ‘Kallmann syndrome presenting as congenital ptosis in brothers’, Clin. Dysmorphol., vol. 16, no. 3, pp. 207–208, Jul. 2007, doi: 10.1097/MCD.0b013e3280b10beb.

J. D. Schwankhaus, J. Currie, M. J. Jaffe, S. R. Rose, and R. J. Sherins, ‘Neurologic findings in men with isolated hypogonadotropic hypogonadism’, Neurology, vol. 39, no. 2 Pt 1, pp. 223–226, Feb. 1989, doi: 10.1212/wnl.39.2.223.

D. Söderlund, P. Canto, and J. P. Méndez, ‘Identification of three novel mutations in the KAL1 gene in patients with Kallmann syndrome’, J. Clin. Endocrinol. Metab., vol. 87, no. 6, pp. 2589–2592, Jun. 2002, doi: 10.1210/jcem.87.6.8611.

J. M. Kirk et al., ‘Unilateral renal aplasia in X-linked Kallmann’s syndrome’, Clin. Genet., vol. 46, no. 3, pp. 260–262, Sep. 1994, doi: 10.1111/j.1399-0004.1994.tb04238.x.

C. Dodé et al., ‘Novel FGFR1 sequence variants in Kallmann syndrome, and genetic evidence that the FGFR1c isoform is required in olfactory bulb and palate morphogenesis’, Hum. Mutat., vol. 28, no. 1, pp. 97–98, Jan. 2007, doi: 10.1002/humu.9470.

M. G. Butler, “Prader-Willi syndrome: Current understanding of cause and diagnosis,” American Journal of Medical Genetics, vol. 35, no. 3. NIH Public Access, pp. 319–332, 1990.

A. Åkefeldt, C. Gillberg, and C. Larsson, “PRADER‐WILLI SYNDROME IN A SWEDISH RURAL COUNTY: EPIDEMIOLOGICAL ASPECTS,” Dev. Med. Child Neurol., vol. 33, no. 8, pp. 715–721, Aug. 1991.

T. Lionti, S. M. Reid, S. M. White, and M. M. Rowell, “A population-based profile of 160 Australians with Prader-Willi syndrome: Trends in diagnosis, birth prevalence and birth characteristics,” Am. J. Med. Genet. Part A, vol. 167, no. 2, pp. 371–378, Feb. 2015.

H. Ehara, K. Ohno, and K. Takeshita, “Frequency of the Prader-Willi syndrome in the San-in district, Japan,” Brain Dev., vol. 17, no. 5, pp. 324–326, Sep. 1995.

J. E. Whittington, A. J. Holland, T. Webb, J. Butler, D. Clarke, and H. Boer, “Population prevalence and estimated birth incidence and mortality rate for people with Prader-Willi syndrome in one UK Health Region

,” Journal of Medical Genetics, vol. 38, no. 11. BMJ Publishing Group Ltd, pp. 792–798, 01-Nov-2001.

M. G. Butler, D. D. Weaver, and F. J. Meaney, “Prader-Willi syndrome: are there population differences?,” Clin. Genet., vol. 22, no. 5, pp. 292–4, Nov. 1982.

S. B. Cassidy, S. Schwartz, J. L. Miller, and D. J. Driscoll, “Prader-Willi syndrome,” Genetics in Medicine, vol. 14, no. 1. Nature Publishing Group, pp. 10–26, 26-Sep-2012.

B. Horsthemke and J. Wagstaff, “Mechanisms of imprinting of the Prader-Willi/Angelman region,” American Journal of Medical Genetics, Part A, vol. 146, no. 16. pp. 2041–2052, 15-Aug-2008.

T. Sahoo et al., “Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster,” Nat. Genet., vol. 40, no. 6, pp. 719–721, Jun. 2008.

M. G. Butler, A. M. Manzardo, and J. L. Forster, “Prader-Willi Syndrome: Clinical Genetics and Diagnostic Aspects with Treatment Approaches.,” Curr. Pediatr. Rev., vol. 12, no. 2, pp. 136–66, 2016.

R. Heksch, M. Kamboj, K. Anglin, and K. Obrynba, “Review of Prader-Willi syndrome: The endocrine approach,” Translational Pediatrics, vol. 6, no. 4. AME Publishing Company, pp. 274–285, 01-Oct-2017.

L. Benchikhi, H. Nafiaa, A. Zaroual, and A. Ouanass, “Psychological management of a patient with prader willi syndrome: Case study of a young moroccan girl,” Pan Afr. Med. J., vol. 33, 2019.

D. R. Brás, P. Semedo, B. C. Picąrra, and R. Fernandes, “Prader-Willi syndrome: A nest for premature coronary artery disease?,” BMJ Case Rep., vol. 2018, 2018.

G. N. Sanjeeva et al., “Clinical and Molecular Characterization of Prader-Willi Syndrome,” Indian J. Pediatr., vol. 84, no. 11, pp. 815–821, Nov. 2017.

W. Merckx, W. Lecot, and K. Titeca, “Psychose bij een patiënt met het syndroom van Prader-Willi.”

V. A. Holm et al., “Prader-Willi syndrome: Consensus diagnostic criteria,” Pediatrics, vol. 91, no. 2, pp. 398–402, 1993.

M. G. Butler, “Management of obesity in Prader-Willi syndrome,” Nature Clinical Practice Endocrinology and Metabolism, vol. 2, no. 11. NIH Public Access, pp. 592–593, Nov-2006.

M. Góralska et al., “Management of Prader-Willi Syndrome (PWS) in adults — What an endocrinologist needs to know. Recommendations of the Polish Society of Endocrinology and the Polish Society of Paediatric Endocrinology and Diabetology,” Endokrynol. Pol., vol. 69, no. 4, pp. 345–355, Sep. 2018.

M. va Langouë et al., “Zinc finger protein 274 regulates imprinted expression of transcripts in Prader-Willi syndrome neurons.”

T. Raivio and P. J. Miettinen, “Constitutional delay of puberty versus congenital hypogonadotropic hypogonadism: Genetics, management and updates,” Best Practice & Research Clinical Endocrinology & Metabolism, vol. 33, no. 3, p. 101316, Jun. 2019.

N. Cano Sokoloff, M. Misra, and K. E. Ackerman, “Exercise, Training, and the Hypothalamic-Pituitary-Gonadal Axis in Men and Women,” Frontiers of Hormone Research, pp. 27–43, 2016.

A. P. Abreu and U. B. Kaiser, “Pubertal development and regulation,” The Lancet Diabetes & Endocrinology, vol. 4, no. 3, pp. 254–264, Mar. 2016.

Ravikumar Balasubramanian and W. F. Crowley, “Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency,”, 02-Mar-2017. [Online]. Available:

U. Boehm et al., “European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment,” Nature Reviews Endocrinology, vol. 11, no. 9, pp. 547–564, Jul. 2015.

G. P. Sykiotis et al., “Oligogenic basis of isolated gonadotropin-releasing hormone deficiency,” Proceedings of the National Academy of Sciences, vol. 107, no. 34, pp. 15140–15144, Aug. 2010.

C. Xu and N. Pitteloud, “Congenital Hypogonadotropic Hypogonadism (Isolated GnRH Deficiency),” Pituitary Disorders of Childhood, pp. 229–250, 2019.

Q.-H. Sun, Y. Zheng, X.-L. Zhang, and Y.-M. Mu, “Role of Gonadotropin-releasing Hormone Stimulation Test in Diagnosing Gonadotropin Deficiency in Both Males and Females with Delayed Puberty,” Chinese Medical Journal, vol. 128, no. 18, pp. 2439–2443, Sep. 2015.

J. Harrington and M. R. Palmert, “Distinguishing Constitutional Delay of Growth and Puberty from Isolated Hypogonadotropic Hypogonadism: Critical Appraisal of Available Diagnostic Tests,” The Journal of Clinical Endocrinology & Metabolism, vol. 97, no. 9, pp. 3056–3067, Sep. 2012.

R. L. Doty, “Office Procedures for Quantitative Assessment of Olfactory Function,” American Journal of Rhinology, vol. 21, no. 4, pp. 460–473, Jul. 2007.

G. P. Wagner and J. Zhang, “The pleiotropic structure of the genotype–phenotype map: the evolvability of complex organisms,” Nature Reviews Genetics, vol. 12, no. 3, pp. 204–213, Feb. 2011.

J. Young et al., “Clinical Management of Congenital Hypogonadotropic Hypogonadism,” Endocrine Reviews, vol. 40, no. 2, pp. 669–710, Jan. 2019.

N. Janssen et al., “Mutation update on the CHD7 gene involved in CHARGE syndrome,” Human Mutation, vol. 33, no. 8, pp. 1149–1160, Apr. 2012.

S. Mehr, P. Hsu, and D. Campbell, “Immunodeficiency in CHARGE syndrome,” American Journal of Medical Genetics Part C: Seminars in Medical Genetics, vol. 175, no. 4, pp. 516–523, Nov. 2017.

C. M. de Geus et al., “Guidelines in CHARGE syndrome and the missing link: Cranial imaging,” American Journal of Medical Genetics Part C: Seminars in Medical Genetics, vol. 175, no. 4, pp. 450–464, Nov. 2017.

A. Hudson, C.-L. Trider, and K. Blake, “CHARGE Syndrome,” Pediatrics in Review, vol. 38, no. 1, pp. 56–59, Jan. 2017.

J. P. Wyllie, M. J. Wright, J. Burn, and S. Hunter, “Natural history of trisomy 13.,” Archives of Disease in Childhood, vol. 71, no. 4, pp. 343–345, Oct. 1994.

G. M. Savva, K. Walker, and J. K. Morris, “The maternal age-specific live birth prevalence of trisomies 13 and 18 compared to trisomy 21 (Down syndrome),” Prenatal Diagnosis, p. n/a-n/a, 2009.

P. A. Levy and R. Marion, “Trisomies,” Pediatrics in Review, vol. 39, no. 2, pp. 104–106, Feb. 2018.

P. Petry et al., “Clinical features and prognosis of a sample of patients with trisomy 13 (Patau syndrome) from Brazil,” American Journal of Medical Genetics Part A, vol. 161, no. 6, pp. 1278–1283, Apr. 2013.

M. Muenke et al., “A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome,” Nature Genetics, vol. 8, no. 3, pp. 269–274, Nov. 1994.

Y. Hassona, A. Al-Hadidi, T. A. Ghlassi, H. E. Dali, and C. Scully, “Pfeiffer syndrome: oral healthcare management and description of new dental findings in a craniosynostosis,” Special Care in Dentistry, vol. 37, no. 5, pp. 258–262, Aug. 2017.

A. Giancotti et al., “Pfeiffer syndrome: literature review of prenatal sonographic findings and genetic diagnosis,” The Journal of Maternal-Fetal & Neonatal Medicine, vol. 30, no. 18, pp. 2225–2231, Oct. 2016.

Radhika Dhamija and Dusica Babovic-Vuksanovic, “Hartsfield Syndrome,”, 03-Mar-2016. [Online]. Available: [Accessed: 09-Apr-2020].

Y. Shi, R. Dhamija, C. Wren, X. Wang, D. Babovic-Vuksanovic, and E. Spector, “Detection of gonadal mosaicism in Hartsfield syndrome by next generation sequencing,” American Journal of Medical Genetics Part A, vol. 170, no. 12, pp. 3359–3359, Sep. 2016.

C. Courage et al., “Novel synonymous and missense variants in FGFR1 causing Hartsfield syndrome,” American Journal of Medical Genetics Part A, vol. 179, no. 12, pp. 2447–2453, Sep. 2019.

M. Takagi et al., “Novel heterozygous mutation in the extracellular domain of FGFR1 associated with Hartsfield syndrome,” Human Genome Variation, vol. 3, no. 1, Oct. 2016.

R. Bhattacharjee, S. Dogra, and K. Vinay, “Waardenburg syndrome: when the eyes speak the truth,” Postgraduate Medical Journal, vol. 95, no. 1120, pp. 102–102, Oct. 2018.

E. Suzuki et al., “Loss-of-Function SOX10 Mutation in a Patient with Kallmann Syndrome, Hearing Loss, and Iris Hypopigmentation,” Hormone Research in Paediatrics, vol. 84, no. 3, pp. 212–216, 2015.

A. Zaman, R. Capper, and W. Baddoo, “Waardenburg syndrome: more common than you think!,” Clinical Otolaryngology, vol. 40, no. 1, pp. 44–48, Jan. 2015.

Y. Izumi et al., “Hypogonadotropic hypogonadism in a female patient previously diagnosed as having waardenburg syndrome due to a sox10 mutation,” Endocrine, vol. 49, no. 2, pp. 553–556, Oct. 2014.

A. Abbasi, N. Butt, B. Sultan, i S. M. Munir, „Hypokalemic paralysis and megaloblastic anaemia in Laurence-Moon-Bardet-Biedl syndrome”, J. Coll. Physicians Surg.--Pak. JCPSP, t. 19, nr 3, s. 186–188, mar. 2009, doi: 03.2009/JCPSP.186188.

A. B. Abdulla i in., „Laurence Moon Bardet Biedl Syndrome”, Mymensingh Med. J. MMJ, t. 18, nr 1 Suppl, s. S124-128, sty. 2009.

S. Priya, S. Nampoothiri, P. Sen, i S. Sripriya, „Bardet–Biedl syndrome: Genetics, molecular pathophysiology, and disease management”, Indian J. Ophthalmol., t. 64, nr 9, s. 620–627, wrz. 2016, doi: 10.4103/0301-4738.194328.

E. N. Suspitsin i E. N. Imyanitov, „Bardet-Biedl Syndrome”, Mol. Syndromol., t. 7, nr 2, s. 62–71, maj 2016, doi: 10.1159/000445491.

G. Pérez-Palacios i in., „Pituitary and gonadal function in patients with the Laurence-Moon-Biedl syndrome”, Acta Endocrinol. (Copenh.), t. 84, nr 1, s. 191–199, sty. 1977, doi: 10.1530/acta.0.0840191.

A. G. Oettle, D. Rabinowitz, i H. C. Seftel, „The Laurence-Moon syndrome with germinal aplasia of the testis: report of a case and review”, J. Clin. Endocrinol. Metab., t. 20, s. 683–699, maj 1960, doi: 10.1210/jcem-20-5-683.

G. Mozaffarian, M. K. Nakhjavani, i A. Farrahi, „The Laurence-Moon-Bardet-Biedl syndrome: unresponsiveness to the action of testosterone, a possible mechanism”, Fertil. Steril., t. 31, nr 4, s. 417–422, kwi. 1979, doi: 10.1016/s0015-0282(16)43940-3.

D. Leroith, Y. Farkash, J. Bar-Ziev, i I. M. Spitz, „Hypothalamic-pituitary function in the Bardet-Biedl syndrome”, Isr. J. Med. Sci., t. 16, nr 7, s. 514–518, lip. 1980.

M. I. Stamou and N. A. Georgopoulos, “Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism,” Metabolism, vol. 86, pp. 124–134, Sep. 2018.

P. E. Carter, J. H. Pearn, J. Bell, N. Martin, i N. G. Anderson, „Survival in trisomy 18: Life tables for use in genetic counselling and clinical paediatrics”, Clin. Genet., t. 27, nr 1, s. 59–61, 1985, doi: 10.1111/j.1399-0004.1985.tb00184.x.

I. D. Young, J. P. Cook, i L. Mehta, „Changing demography of trisomy 18.”, Arch. Dis. Child., t. 61, nr 10, s. 1035–1036, paź. 1986, doi: 10.1136/adc.61.10.1035.

S. Root i J. C. Carey, „Survival in trisomy 18”, Am. J. Med. Genet., t. 49, nr 2, s. 170–174, sty. 1994, doi: 10.1002/ajmg.1320490203.

N. D. Embleton, J. P. Wyllie, M. J. Wright, J. Burn, i S. Hunter, „Natural history of trisomy 18.”, Arch. Dis. Child. Fetal Neonatal Ed., t. 75, nr 1, s. F38–F41, lip. 1996.

S. A. Rasmussen, L.-Y. C. Wong, Q. Yang, K. M. May, i J. M. Friedman, „Population-based analyses of mortality in trisomy 13 and trisomy 18”, Pediatrics, t. 111, nr 4 Pt 1, s. 777–784, kwi. 2003, doi: 10.1542/peds.111.4.777.

„Neonatal management of trisomy 18: Clinical details of 24 patients receiving intensive treatment - Kosho - 2006 - American Journal of Medical Genetics Part A - Wiley Online Library”. (udostępniono kwi. 08, 2020).

S. Kukora, J. Firn, N. Laventhal, C. Vercler, B. Moore, i J. D. Lantos, „Infant With Trisomy 18 and Hypoplastic Left Heart Syndrome”, Pediatrics, t. 143, nr 5, maj 2019, doi: 10.1542/peds.2018-3779.

K. G. Kupke i U. Müller, „Parental origin of the extra chromosome in trisomy 18.”, Am. J. Hum. Genet., t. 45, nr 4, s. 599–605, paź. 1989.

J. M. Fisher, J. F. Harvey, N. E. Morton, i P. A. Jacobs, „Trisomy 18: studies of the parent and cell division of origin and the effect of aberrant recombination on nondisjunction.”, Am. J. Hum. Genet., t. 56, nr 3, s. 669–675, mar. 1995.

M. Bugge i in., „Non-disjunction of chromosome 18”, Hum. Mol. Genet., t. 7, nr 4, s. 661–669, kwi. 1998, doi: 10.1093/hmg/7.4.661.

D. Bettio, P. Levi Setti, P. Bianchi, i V. Grazioli, „Trisomy 18 mosaicism in a woman with normal intelligence”, Am. J. Med. Genet. A., t. 120A, nr 2, s. 303–304, lip. 2003, doi: 10.1002/ajmg.a.20213.

M. E. Tucker, H. J. Garringer, i D. D. Weaver, „Phenotypic spectrum of mosaic trisomy 18: two new patients, a literature review, and counseling issues”, Am. J. Med. Genet. A., t. 143A, nr 5, s. 505–517, mar. 2007, doi: 10.1002/ajmg.a.31535.

E. Gersdorf, B. Utermann, i G. Utermann, „Trisomy 18 mosaicism in an adult woman with normal intelligence and history of miscarriage”, Hum. Genet., t. 84, nr 3, s. 298–299, luty 1990, doi: 10.1007/BF00200581.

M. Ukita, M. Hasegawa, i T. Nakahori, „Trisomy 18 mosaicism in a woman with normal intelligence, pigmentary dysplasia, and an 18 trisomic daughter”, Am. J. Med. Genet., t. 68, nr 2, s. 240–241, sty. 1997, doi: 10.1002/(sici)1096-8628(19970120)68:2<240::aid-ajmg24>;2-t.

H. Goldstein i K. G. Nielsen, „Rates and survival of individuals with trisomy 13 and 18. Data from a 10-year period in Denmark”, Clin. Genet., t. 34, nr 6, s. 366–372, grudz. 1988, doi: 10.1111/j.1399-0004.1988.tb02894.x.

G. N. Wilson, „Karyotype/phenotype correlation: prospects and problems illustrated by trisomy 18”, Prog. Clin. Biol. Res., t. 384, s. 157–173, 1993.

L. Boghosian-Sell i in., „Molecular mapping of the Edwards syndrome phenotype to two noncontiguous regions on chromosome 18”, Am. J. Hum. Genet., t. 55, nr 3, s. 476–483, wrz. 1994.

D. W. Smith, „AUTOSOMAL ABNORMALITIES”, Am. J. Obstet. Gynecol., t. 90, s. SUPPL:1055-1077, grudz. 1964, doi: 10.1016/0002-9378(64)90835-x.

R. W. Marion i in., „Trisomy 18 score: a rapid, reliable diagnostic test for trisomy 18”, J. Pediatr., t. 113, nr 1 Pt 1, s. 45–48, lip. 1988, doi: 10.1016/s0022-3476(88)80526-2.

M. E. Hodes, J. Cole, C. G. Palmer, i T. Reed, „Clinical experience with trisomies 18 and 13.”, J. Med. Genet., t. 15, nr 1, s. 48–60, luty 1978.

M. Kinoshita i in., „Thirty-one autopsy cases of trisomy 18: clinical features and pathological findings”, Pediatr. Pathol., t. 9, nr 4, s. 445–457, 1989, doi: 10.3109/15513818909022365.

L. Teixeira i in., „Defective migration of neuroendocrine GnRH cells in human arrhinencephalic conditions”, J. Clin. Invest., t. 120, nr 10, s. 3668–3672, paź. 2010, doi: 10.1172/JCI43699.

R. F. M. Rosa, R. C. M. Rosa, P. R. G. Zen, C. Graziadio, i G. A. Paskulin, „Trisomy 18: review of the clinical, etiologic, prognostic, and ethical aspects”, Rev. Paul. Pediatr., t. 31, nr 1, s. 111–120, mar. 2013, doi: 10.1590/S0103-05822013000100018.

C. V. Isaksen, B. Ytterhus, i S. Skarsvåg, „Detection of trisomy 18 on formalin-fixed and paraffin-embedded material by fluorescence in situ hybridization”, Pediatr. Dev. Pathol. Off. J. Soc. Pediatr. Pathol. Paediatr. Pathol. Soc., t. 3, nr 3, s. 249–255, cze. 2000, doi: 10.1007/s100249910032.

E. Z. Chen i in., „Noninvasive Prenatal Diagnosis of Fetal Trisomy 18 and Trisomy 13 by Maternal Plasma DNA Sequencing”, PLOS ONE, t. 6, nr 7, s. e21791, lip. 2011, doi: 10.1371/journal.pone.0021791.

T. Khaper i in., „Increasing incidence of optic nerve hypoplasia/septo-optic dysplasia spectrum: Geographic clustering in Northern Canada”, Paediatr. Child Health, t. 22, nr 8, s. 445–453, lis. 2017, doi: 10.1093/pch/pxx118.

E. Garne i in., „Epidemiology of septo-optic dysplasia with focus on prevalence and maternal age - A EUROCAT study”, Eur. J. Med. Genet., t. 61, nr 9, s. 483–488, wrz. 2018, doi: 10.1016/j.ejmg.2018.05.010.

L. Saranac i Z. Gucev, „New insights into septo-optic dysplasia”, Pril. Makedon. Akad. Na Nauk. Umet. Oddelenie Za Med. Nauki, t. 35, nr 1, s. 123–127, 2014.

E. A. Webb i M. T. Dattani, „Septo-optic dysplasia”, Eur. J. Hum. Genet. EJHG, t. 18, nr 4, s. 393–397, kwi. 2010, doi: 10.1038/ejhg.2009.125.

K. Nagasaki i in., „Clinical characteristics of septo-optic dysplasia accompanied by congenital central hypothyroidism in Japan”, Clin. Pediatr. Endocrinol., t. 26, nr 4, s. 207–213, 2017, doi: 10.1297/cpe.26.207.

M. Ganau, S. Huet, N. Syrmos, M. Meloni, i J.

Jayamohan, „Neuro-Ophthalmological Manifestations Of Septo-Optic Dysplasia: Current Perspectives”, Eye Brain, t. 11, s. 37–47, paź. 2019, doi: 10.2147/EB.S186307.

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Journal of Education, Health and Sport formerly Journal of Health Sciences

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Editors indicates that the main version of the magazine is to issue a "electronic".

The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019.

1223 Journal of Education, Health and Sport eISSN 2391-8306 7

ISSN 2391-8306 formerly ISSN: 1429-9623 / 2300-665X

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ICV 2019 = 100.00 ICV 2018 = 95.95 ICV 2017 = 91.30 ICV 2016 = 84.69 ICV 2015 = 93.34 ICV 2014 = 89.51 Standardized Value: 8.27 ICV 2013: 7.32 ICV 2012: 6.41 ICV 20115.48

RG Journal Impact: 0.18 *

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2020Available summer 2021
2018 / 20190.18

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