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Interdisciplinary CompetenceMolecular Diagnostics
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IllnessHypogonadism, female hypergonadotropic; differential diagnosis A

Summary

Short information

Comprehensive differential diagnostic panel for female hypergonadotropic Hypogonadism comprising 15 and altogether 27 curated genes according to the clinical signs

ID
HP8855
Number of genes
25 Accredited laboratory test
Examined sequence length
28,1 kb (Core-/Core-canditate-Genes)
45,6 kb (Extended panel: incl. additional genes)
Analysis Duration
on request
Material
  • EDTA-anticoagulated blood (3-5 ml)
Diagnostic indications

NGS +

[Sanger]

 

Gene panel

Selected genes

NameExon Length (bp)OMIM-GHeredity
BMP151179XL
CYP17A11527AR
CYP19A11512AR
EIF2B52166AR
FIGLA660AD
FOXL21131AD
FSHR2088AR
GALT1140AR
HFM14308AR
MCM82523AR
MCM93432AR
NOBOX2076AD
NR5A11386AD, AR
POF1B1770XLR
SOHLH11164AR
AIRE1638AD, AR
DIAPH23306XLD
EIF2B21056AR
EIF2B41569AR
FMR11899XL
GDF91365AD, AR
POU5F11083AD
PSMC3IP654AR
SOHLH21278AD
STAG33678AR

Informations about the disease

Clinical Comment

Hypergonadotropic hypogonadism is characterized by low levels of sex hormones and increased gonadotropins in females with a 46XX karyotype. In girls, puberty is delayed, and in initially inconspicuous women hypergonadotropic hypogonadism leads to primary ovarian insufficiency (POI), which is defined by development before age 40 resembling menopause. In addition to infertility, women with POI are at increased risk for a number of comorbidities, including osteoporosis as well as increased cardiovascular morbidity and mortality. The genetic disorders rarely include (a late diagnosed) 45X Turner syndrome, more commonly pre-mutations in the Fragile X Mental Retardation Type 1 (FMR1) gene in up to 15% of cases, but also monogenic syndromic or non-syndromic disorders. Two thirds of these cases remain primarily unexplained, although idiopathic hypergonadotropic hypogonadism may be associated with mutations in a variety of different genes. Using NGS approaches genetic alterations may be detected in up to 25% of cases with female hypergonadotropic hypogonadism. Therefore, a negative molecular genetic finding excludes by no means the clinical diagnosis.

References: doi: 10.1007/s12020-021-02626-z

doi: 10.1210/jendso/bvz037.

 

Synonyms
  • Allelic: 46XX sex reversal 4 (NR5A1)
  • Allelic: 46XY sex reversal 3 (NR5A1)
  • Allelic: Adrenocortical insufficiency (NR5A1)
  • Allelic: Aromatase excess syndrome (CYP19A1)
  • Allelic: Blepharophimosis, epicanthus inversus + ptosis, type 1 + 2 (FOXL2)
  • Allelic: Leukoencephalopathy with vanishing white matter (EIF2B2)
  • Allelic: Leukoencephalopathy with vanishing white matter (EIF2B4)
  • Allelic: Leukoencephalopathy with vanishing white matter (EIF2B5)
  • Allelic: Spermatogenic failure 32 (SOHLH1)
  • Allelic: Spermatogenic failure 52 (C14orf39)
  • Allelic: Spermatogenic failure 8 (NR5A1)
  • 17,20-lyase deficiency, isolated (CYP17A1)
  • 17-alpha-hydroxylase/17,20-lyase deficiency (CYP17A1)
  • Allelic: Spermatogenic failure 15 (SYCE1)
  • Aromatase deficiency (CYP19A1)
  • Autoimmune polyendocrinopathy syndrome type I, with/-out reversible metaphyseal dysplasia (AIRE)
  • Galactosemia (GALT)
  • Ovarian dysgenesis 1 (FSHR)
  • Ovarian dysgenesis 2 (BMP15)
  • Ovarian dysgenesis 3 (PSMC3IP)
  • Ovarian dysgenesis 4 (MCM9)
  • Ovarian dysgenesis 5 (SOHLH1)
  • Ovarian hyperstimulation syndrome (FSHR)
  • Ovarian response to FSH stimulation (FSHR)
  • Ovarioleukodystrophy (EIF2B2)
  • Ovarioleukodystrophy (EIF2B4)
  • Ovarioleukodystrophy (EIF2B5)
  • Premature ovarian failure 1 (FMR1, 55-200 CCG repeats)
  • Premature ovarian failure 12 (SYCE1)
  • 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)
Heredity, heredity patterns etc.
  • AD
  • AR
  • XL
  • XLD
  • XLR
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code
E28.3

Bioinformatics and clinical interpretation

No text defined