Klinische FragestellungHypogonadismus, hypogonadotroper; Differentialdiagnose

NGS +

[Sanger]

Hypogonadotroper Hypogonadismus (HH) ist entweder auf niedrige Konzentrationen von Sexualsteroiden (Östrogen, Progesteron) oder von Gonadotropinen (FSH, LH) zurückzuführen mit hypothalamischen oder hypophysären Ursachen. Die Mehrheit der Fälle wird bei Männern diagnostiziert; bei Frauen tritt in der Regel eine primäre Amenorrhoe auf, die oft nicht genetisch bedingt ist. HH kann kongenital oder später auftreten bzw. zumeist mit 18 Jahren definitiv diagnostiziert werden. Die Detektionsrate ist bei konnatalem HH (35-60%) deutlich höher als bei verspäteter Pubertätsentwicklung als Ausdruck von später manifestierten HH-Formen, die klinisch nicht unterschieden werden können. Aussagen zu Penetranzraten und Expressivität müssen Gen- bzw. Mutations-bezogen getroffen werden. Ein unauffälliger genetischer Befund bedeutet sicherlich keinen Ausschluss der klinischen Verdachtsdiagnose.

Referenz: https://www.nature.com/articles/nrendo.2015.112

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520594/

• Allelic: CHARGE syndrome (CHD7)
• Allelic: Encephalocraniocutaneous lipomatosis, somatic mosaic (FGFR1)
• Allelic: Encephalocraniocutaneous lipomatosis; Hartsfield syndrome; Jackson-Weiss syndrome (FGFR1)
• Allelic: Fascioscapulohumeral muscular dystrophy 2, digenic (SMCHD1)
• Allelic: Hartsfield syndrome (FGFR1)
• Allelic: Holoprosencephaly 9 (GLI2)
• Allelic: Jackson-Weiss syndrome (FGFR1)
• Allelic: Laurence-Moon syndrome (PNPLA6)
• Allelic: Microphthalmia, syndromic 3 (SOX2)
• Allelic: Obesity, susceptibility to, BMIQ12 (PCSK1)
• Allelic: Obesity, susceptibility to, BMIQ14 (FTO)
• Allelic: Oliver-McFarlane syndrome (PNPLA6)
• Allelic: Osteoglophonic dysplasia (FGFR1)
• Allelic: Osteoglophonic dysplasia; Pfeiffer syndrome; Trigonocephaly 1 (FGFR1)
• Allelic: PCWH syndrome (SOX10)
• Allelic: Pfeiffer syndrome (FGFR1)
• Allelic: Precocious puberty, central, 1 (KISS1R)
• Allelic: Septooptic dysplasia (HESX1)
• Allelic: Spastic paraplegia 39, AR (PNPLA6)
• Allelic: Treacher Collins syndrome 3 (POLRR1C)
• Allelic: Trigonocephaly 1 (FGFR1)
• Allelic: Wiedemann-Rautenstrauch syndrome (POLR3A)
• 46XY sex reversal 2, dosage-sensitive (NR0B1)
• Adrenal hypoplasia, congenital (NR0B1)
• Allelic: Blood group, John-Milton-Hagen system (SEMA7A)
• Allelic: Luteinizing hormone resistance, female (LHCGR)
• Allelic: Precocious puberty, male (LHCGR)
• Alopecia, neurologic defects + endocrinopathy syndrome (RBM28)
• Bardet-Biedl syndrome genes (Rp, obesity, kidney dysfunction, hypogonadism...)
• Bosma arhinia microphthalmia syndrome (SMCHD1)
• Boucher-Neuhauser syndrome (PNPLA6)
• CHARGE syndrome (SEMA3E)
• Cerebellar ataxia + hypogonadotropic hypogonadism (RNF216)
• Congenital hypogonadotropic hypogonadism (KLB)
• Congenital hypogonadotropic hypogonadism [MONDO:0015770] (CCDC141)
• Craniosynostosis 3 (TCF12)
• Culler-Jones syndrome (GLI2)
• Fibrosis of extraocular muscles, congenital, 3A (TUBB3)
• Growth hormone deficiency with pituitary anomalies (HESX1)
• Growth retardation, developmental delay, facial dysmorphism (FTO)
• Hemochromatosis (HFE)
• Hemochromatosis, type 2B (HAMP)
• Hemochromatosis, type 3 (TFR2)
• Hemochromatosis, type 4 (SLC40A1)
• Histiocytosis-lymphadenopathy plus syndrome (SLC29A3)
• Hypogonadotropic hypogonadism 1 with/-out anosmia; Kallmann syndrome 1 (ANOS1)
• Hypogonadotropic hypogonadism 10 with/-out anosmia (TAC3)
• Hypogonadotropic hypogonadism 11 with/-out anosmia (TACR3)
• Hypogonadotropic hypogonadism 12 with/-out anosmia (GNRH1)
• Hypogonadotropic hypogonadism 13 with/-out anosmia (KISS1)
• Hypogonadotropic hypogonadism 14 with/-out anosmia (WDR11)
• Hypogonadotropic hypogonadism 15 with/-out anosmia (HS6ST1)
• Hypogonadotropic hypogonadism 16 with/-out anosmia (SEMA3A)
• Hypogonadotropic hypogonadism 17 with/-out anosmia (SPRY4)
• Hypogonadotropic hypogonadism 18 with/-out anosmia (IL17RD)
• Hypogonadotropic hypogonadism 19 with/_out anosmia (DUSP6)
• Hypogonadotropic hypogonadism 2 with/-out anosmia (FGFR1)
• Hypogonadotropic hypogonadism 20 with/-out anosmia (FGF17)
• Hypogonadotropic hypogonadism 21 with anosmia (FLRT3)
• Hypogonadotropic hypogonadism 22, with/-out anosmia (FEZF1)
• Hypogonadotropic hypogonadism 23 with/-out anosmia (LHB)
• Hypogonadotropic hypogonadism 24 without anosmia (FSHB)
• Hypogonadotropic hypogonadism 25 with anosmia (NDNF)
• Hypogonadotropic hypogonadism 3 with/-out anosmia (PROKR2)
• Hypogonadotropic hypogonadism 4 with/-out anosmia (PROK2)
• Hypogonadotropic hypogonadism 5 with/-out anosmia (CHD7)
• Hypogonadotropic hypogonadism 6 with/-out anosmia (FGF8)
• Hypogonadotropic hypogonadism 7 without anosmia (GNRHR)
• Hypogonadotropic hypogonadism 8 with/-out anosmia (KISS1R)
• Hypogonadotropic hypogonadism 9 with/_out anosmia (NSMF)
• Hypogonadotropic hypogonadism [MONDO:0018555] (SEMA3F)
• Hypogonadotropic hypogonadism without anosmia; normosmic IHH [panelapp] (CCDC141)
• Hypogonadotropic hypogonadism, delayed puberty, primary ovary insufficiency [panelapp] (IGSF10)
• Intellectual developmental disorder + hypogonadotropic hypogonadism (CPE)
• Isolated GnRH deficiency [genereviews] (AXL)
• Isolated GnRH deficiency [genereviews] (SRA1)
• Leukodystrophy, hypomyelinating, 11 (POLR1C)
• Leukodystrophy, hypomyelinating, 7, with/-out oligodontia and/or hypogon. hypogonadism (POLR3A)
• Leukodystrophy, hypomyelinating, 8, with/-out oligodontia and/or hypogon. hypogonadism (POL3RB)
• Leydig cell hypoplasia with hypergonadotropic hypogonadism (LHCGR)
• Martsolf syndrome 1 (RAB3GAP2)
• Martsolf syndrome 2 (RAB3GAB1)
• Mental retardation, XL, syndromic 15 [Cabezas type] (CUL4B)
• Obesity with impaired prohormone processing (PCSK1)
• Obesity, morbid, due to leptin deficiency (LEP)
• Obesity, morbid, due to leptin receptor deficiency (LEPR)
• Optic nerve hypoplasia + abnormalities of the central nervous system (SOX2)
• PCWH syndrome (SOX10)
• Perrault syndrome 3 (CLPP)
• Pituitary hormone deficiency, combined, 1 (POUF1)
• Pituitary hormone deficiency, combined, 2 (PROP1)
• Pituitary hormone deficiency, combined, 3 (LHX3)
• Pituitary hormone deficiency, combined, 4 (LHX4)
• Pituitary hormone deficiency, combined, 5 (HESX1)
• Prader-Willi syndrome (NDN, SIM1, SNRPN)
• Spinocerebellar ataxia, AR 16 (STUB1)
• Waardenburg syndrome, type 2E, with/-out neurologic involvement (SOX10)
• Waardenburg syndrome, type 4C (SOX10)
• Warburg micro syndrome 1 (RAB3GAP1)
• Warburg micro syndrome 2 (RAB3GAP2)
• Woodhouse-Sakati syndrome (DCAF17)