Klinische FragestellungPOI - Prämature Ovarial-Insuffizienz, Differentialdiagnose

NGS +

Sanger

Die vorzeitige oder primäre Ovarialinsuffizienz (POI) ist ein klinisches Syndrom mit Verlust der Ovarialaktivität vor dem 40. Lebensjahr. POI ist durch Menstruationsstörungen (Amenorrhoe/ Oligomenorrhoe) mit erhöhten Gonadotropinen und niedrigem Östradiol gekennzeichnet und weist eine Prävalenz von 1% auf. POI tritt bei (prä-)pubertären Mädchen und Frauen ab dem zweiten Jahrzehnt auf. Zu den Folgen von POI gehören eine verringerte Lebenserwartung, vor allem aufgrund von Herz-Kreislauf-Erkrankungen sowie verringerter Knochendichte. Negative Auswirkungen können das psychische Wohlbefinden, die Lebensqualität und Sexualität betreffen. Daher ist mitunter Hormonersatztherapie indiziert, nachdem spezielle Probleme (Turner-Syndrom, Brustkrebs etc.) mit in Betracht gezogen wurden. Nach Karyotyp- und Fragiles-X-Prämutationstests umfassen molekulargenetische Analysen eine Reihe von autosomalen und X-chromosomalen Genen. Während 20% der Frauen mit Fragiles-X-Prämutationen POI entwickeln, ist die Detektionsrate in den anderen Genen niedriger. Daher schließt ein normales DNA-Ergebnis genetische POI-Ursachen keinesfalls aus.

Referenz: https://www.eshre.eu/Guidelines-and-Legal/Guidelines/Management-of-premature-ovarian-insufficiency.aspx

Der FSHR-Polymorphismus p.Asn680Ser kann hinsichtlich der Dosisberechnung vor ovarieller Stimulation relevant sein und wird daher bei expliziter Anforderung mit ausberichtet. doi: 10.1007/s00129-021-04785-6

• Alias: Follicular stimulating hormone-resistant ovaries
• Alias: Hypergonadotropic ovarian dysgenesis
• Alias: Ovarian insufficiency
• Alias: POI (POF) - premature ovarian insufficiency (failure)
• Alias: Vorzeitige Ovarialinsuffizienz
• Alle3lic: Mitochondrial DNA depletion syndrome 7 [hepatocerebral type] (TWNK)
• Allelic: 46XX sex reversal 4 (NR5A1)
• Allelic: 46XY sex reversal 3 (NR5A1)
• Allelic: Acromesomelic dysplasia, Demirhan type (BMPR1B)
• Allelic: Adrenocortical insufficiency (NR5A1)
• Allelic: Aromatase excess syndrome (CYP19A1)
• Allelic: Blepharophimosis, epicanthus inversus + ptosis, type 1 + 2 (FOXL2)
• Allelic: Brachydactyly, type A1, D + A2 (BMPR1B)
• Allelic: Brachydactyly, type B2 (NOG)
• Allelic: Cardiomyopathy, dilated, 1A (LMNA)
• Allelic: Charcot-Marie-Tooth disease, type 2B1 (LMNA)
• Allelic: Combined oxidative phosphorylation deficiency 8 (AARS2)
• Allelic: D-bifunctional protein deficiency (HSD17B4)
• Allelic: Emery-Dreifuss muscular dystrophy 2, AD (LMNA)
• Allelic: Emery-Dreifuss muscular dystrophy 3, AR (LMNA)
• Allelic: Galloway-Mowat syndrome 7 (NUP107)
• Allelic: Heart-hand syndrome, Slovenian type (LMNA)
• Allelic: Hutchinson-Gilford progeria (LMNAA)
• Allelic: Leukoencephalopathy with vanishing white matter (EIF2B5, EIF2B5)
• Allelic: Leydig cell adenoma, somatic, with precocious puberty (LHCGR)
• Allelic: Leydig cell hypoplasia with hypergonadotropic hypogonadism (LHCGR)
• Allelic: Leydig cell hypoplasia with pseudohermaphroditism (LHCGR)
• Allelic: Lipodystrophy, familial partial, type 2 (LMNA)
• Allelic: Mandibuloacral dysplasia (LMNA)
• Allelic: Mitochondrial DNA depletion syndrome 4A {Alpers type] (POLG)
• Allelic: Mitochondrial DNA depletion syndrome 4B [MNGIE type] (POLG)
• Allelic: Mitochondrial recessive ataxia syndrome [includes SANDO + SCAE] (POLG)
• Allelic: Mosaic variegated aneuploidy syndrome 1 (BUB1B)
• Allelic: Multiple synostoses syndrome 1 (NOG)
• Allelic: Muscular dystrophy, congenital (LMNA)
• Allelic: Nephrotic syndrome, type 11 (NUP107)
• Allelic: Non-obstructive azoospermia (MSH4)
• Allelic: Ovarian response to FSH stimulation (FSHR)
• Allelic: Precocious puberty, male (LHCGR)
• Allelic: Premature chromatid separation trait (BUB1B)
• Allelic: Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 3 (TWNK)
• Allelic: Progressive external ophthalmoplegia, AD 1 (POLG)
• Allelic: Progressive external ophthalmoplegia, AR 1 (POLG)
• Allelic: Restrictive dermopathy, lethal (LMNA)
• Allelic: Spermatogenic failure 1 (SYCE1)
• Allelic: Spermatogenic failure 32 (SOHLH1)
• Allelic: Spermatogenic failure 52 (C14orf39)
• Allelic: Spermatogenic failure 8 (NR5A1)
• Allelic: Spinal and bulbar muscular atrophy of Kennedy (AR CAG)
• Allelic: Stapes ankylosis with broad thumbs + toes (NOG)
• Allelic: Symphalangism, proximal, 1A (NOG)
• Allelic: Tarsal-carpal coalition syndrome (NOG)
• 17,20-lyase deficiency, isolated (CYP17A1)
• 17-alpha-hydroxylase/17,20-lyase deficiency (CYP17A1)
• Allelic: Hypogonadotropic hypogonadism 23 +/- anosmia (LHB)
• Allelic: Leydig cell hypoplasia with hypergonadotropic hypogonadism (LHCGR)
• Allelic: Leydig cell hypoplasia with pseudohermaphroditism (LHCGR)
• Allelic: Precocious puberty, male (LHCGR)
• Aromatase deficiency (CYP19A1)
• Autoimmune polyendocrinopathy, type I, with/-out reversible metaphyseal dysplasia (AIRE)
• Congenital disorder of glycosylation, type Ia (PMM2)
• Galactosemia (GALT)
• Hypogonadotropic hypogonadism 24 without anosmia (FSHB)
• Leukoencephalopathy, progressive, with ovarian failure (AARS2)
• Luteinizing hormone resistance, female (LHCGR)
• Malouf syndrome (LMNA)
• Muscular dystrophy, congenital hearing loss + ovarian insufficiency syndrome (GGPS1)
• Ovarian dysgenesis 1 (FSHR)
• Ovarian dysgenesis 2 (BMP15)
• Ovarian dysgenesis 3 (PSMC3IP)
• Ovarian dysgenesis 4 (MCM9)
• Ovarian dysgenesis 5 (SOHLH1)
• Ovarian dysgenesis 6 (NUP107)
• Ovarian hyperstimulation syndrome (FSHR)
• Ovarioleukodystrophy (EIF2B4, EIF2B5)
• Perrault syndrome 1 (HSD17B4)
• Perrault syndrome 3 (CLPP)
• Perrault syndrome 5 (TWNK)
• Perrault syndrome [panelapp] (SGO2)
• Premature ovarian failure 1 (POF1; FMR1, 55-200 CCG repeats)
• Premature ovarian failure 10 (MCM8)
• Premature ovarian failure 12 (SYCE1)
• Premature ovarian failure 13 (MSH5)
• Premature ovarian failure 14 (GDF9)
• Premature ovarian failure 18 (C14orf39)
• Premature ovarian failure 2A (DIAPH2)
• Premature ovarian failure 2B (POF1B)
• Premature ovarian failure 3 (FOXL2)
• Premature ovarian failure 4 (BMP15)
• Premature ovarian failure 5 (NOBOX)
• Premature ovarian failure 6 (FIGLA)
• Premature ovarian failure 7 (NR5A1)
• Premature ovarian failure 8 (STAG3)
• Premature ovarian failure 9 (HFM1)
• Premature ovarian failure [panelapp] (BUB1B)
• Premature ovarian failure [panelapp] (EIF4ENIF1)
• Premature ovarian failure [panelapp] (KHDRBS1)
• Premature ovarian insufficiency [panelapp] (BMPR1B)
• Premature ovarian insufficiency [panelapp] (DACH2)
• Premature ovarian insufficiency [panelapp] (PGRMC1)
• Primary ovarian failure [MONDO:0005387] (MSH4)
• Primary ovarian insufficiency [panelapp] (EIF4ENIF1)
• Primary ovarian insufficiency [panelapp] (NANOS3)
• Primary ovarian insufficiency [panelapp] (NOG)
• Primary ovarian insufficiency [panelapp] (POLR2C)
• Primary ovarian insufficiency [panelapp] (POLR3H)
• Primary ovarian insufficiency [panelapp] (POU5F1)
• Primary ovarian insufficiency [panelapp] (SOHLH2)
• Primary ovarian insufficiency [panelapp] (SYCP2L)
• Retinal dystrophy with/-out extraocular anomalies (RCBTB1)